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Trial record 20 of 157 for:    Diseases | ( Map: Costa Rica )

Prospective Randomized Evaluation Of Celecoxib Integrated Safety Vs Ibuprofen Or Naproxen (PRECISION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00346216
Recruitment Status : Completed
First Posted : June 29, 2006
Results First Posted : May 1, 2017
Last Update Posted : June 19, 2017
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: celecoxib
Drug: Ibuprofen
Drug: Naproxen
Enrollment 24081
Recruitment Details The study was conducted at 950 centers in Australia (11), Brazil (30), Canada (64), Colombia (7), Costa Rica (12), Hong Kong (4), Mexico (11), Panama (2), Peru (5), Philippines (8), Taiwan (10), Ukraine 19), and United States (767); a total of 24 sites were activated but did not randomized any subject.
Pre-assignment Details All eligible participants were enrolled in to the study.
Arm/Group Title Celecoxib Ibuprofen Naproxen
Hide Arm/Group Description Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Period Title: Overall Study
Started 8072 8040 7969
Completed 5664 5580 5621
Not Completed 2408 2460 2348
Reason Not Completed
Not specified             181             231             205
No longer willing to participate             600             606             585
Withdrawal by Subject             661             692             651
Lost to Follow-up             611             588             542
Physician Decision             80             76             59
Does not meet entrance criteria             13             10             8
Death             189             192             228
Study terminated by sponsor             11             4             8
Missing Subject Summary Status             62             61             62
Arm/Group Title Celecoxib Ibuprofen Naproxen Total
Hide Arm/Group Description Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily. Total of all reporting groups
Overall Number of Baseline Participants 8072 8040 7969 24081
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8072 participants 8040 participants 7969 participants 24081 participants
63.0  (9.5) 63.2  (9.4) 63.3  (9.4) 63.2  (9.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8072 participants 8040 participants 7969 participants 24081 participants
Female
5175
  64.1%
5174
  64.4%
5096
  63.9%
15445
  64.1%
Male
2897
  35.9%
2866
  35.6%
2873
  36.1%
8636
  35.9%
1.Primary Outcome
Title The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC).
Hide Description APTC events are defined as a composite of any of the following events: Death due to CV causes (including cardiac, cerebrovascular, venous thromboembolic, haemorrhagic, other vascular, or unknown cause); Non-fatal MI; Non-fatal stroke (including intracranial hemorrhages, stroke of ischemic or unknown etiology).
Time Frame Intent to Treat (ITT) Population - 30 months; Modified ITT (MITT) Population - 42 months
Hide Outcome Measure Data
Hide Analysis Population Description

ITT - The ITT population will consist of all subjects randomized for participation in the study.

MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.

Arm/Group Title Celecoxib Ibuprofen Naproxen
Hide Arm/Group Description:
Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily
Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily
Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Overall Number of Participants Analyzed 8072 8040 7969
Measure Type: Number
Unit of Measure: Percentage of Partcipants
ITT (N = 8072, 8040, 7969) 2.3 2.7 2.5
MITT (N = 8030, 7990, 7933) 1.7 1.9 1.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments ITT Population
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non inferiority required a hazard ratio of 1.12 or lower, as well as an upper 95% confidence limit of 1.33 or lower in the ITT population and of 1.40 or lower in the MITT population.
Statistical Test of Hypothesis P-Value 0.0002
Comments Non inferiority P value, α=0.025
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.76 to 1.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments MITT Population
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority requires the hazard ratio does not exceed 1.12, and the upper bound of the two-sided 95% CI for the hazard ratio estimate does not exceed 1.40
Statistical Test of Hypothesis P-Value 0.0001
Comments Non inferiority P value, α=0.025
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.72 to 1.14
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments ITT Population
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority requires the hazard ratio does not exceed 1.12, and the upper bound of the two-sided 95% CI for the hazard ratio estimate does not exceed 1.33
Statistical Test of Hypothesis P-Value <0.0001
Comments Non inferiority P value, α=0.025
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.70 to 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments MITT Population
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority requires the hazard ratio does not exceed 1.12, and the upper bound of the two-sided 95% CI for the hazard ratio (HR) estimate does not exceed 1.40
Statistical Test of Hypothesis P-Value <0.0001
Comments Non-inferiority P-value, α=0.025
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.64 to 1.02
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments ITT Population
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority requires the hazard ratio does not exceed 1.12, and the upper bound of the two-sided 95% CI for the hazard ratio (HR) estimate does not exceed 1.33
Statistical Test of Hypothesis P-Value 0.0182
Comments Non-inferiority P-value, α=0.025
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.89 to 1.31
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments MITT Population
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority requires the hazard ratio does not exceed 1.12, and the upper bound of the two-sided 95% CI for the hazard ratio (HR) estimate does not exceed 1.40
Statistical Test of Hypothesis P-Value 0.0250
Comments Non-inferiority P-value, α=0.025
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.89 to 1.40
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The First Occurrence of a Major Adverse Cardiovascular Events (MACE)
Hide Description MACE defined as the composite of CV death (including hemorrhagic death), non-fatal MI, non-fatal stroke, hospitalization for UA, revascularization or hospitalization for TIA
Time Frame ITT Population - 30 months; MITT Population - 42 months
Hide Outcome Measure Data
Hide Analysis Population Description

ITT - The ITT population will consist of all subjects randomized for participation in the study.

MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.

Arm/Group Title Celecoxib Ibuprofen Naproxen
Hide Arm/Group Description:
Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily
Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily
Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Overall Number of Participants Analyzed 8072 8040 7969
Measure Type: Number
Unit of Measure: Percentage of Participants
ITT (N = 8072, 8040, 7969) 4.2 4.8 4.3
MITT (N = 8030, 7990, 7933) 3.1 3.6 3.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments ITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6427
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.83 to 1.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments ITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0597
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.75 to 1.01
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments ITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1481
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.96 to 1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments MITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5758
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.80 to 1.13
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments MITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0204
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.69 to 0.97
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments MITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0751
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.98 to 1.38
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE)
Hide Description CSGIE include: Gastroduodenal (GD) hemorrhage, Gastric outlet obstruction, Gastroduodenal, small bowel or large bowel perforation, Large bowel hemorrhage, Small bowel hemorrhage, Acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage, Symptomatic gastric or duodenal ulcer
Time Frame ITT Population - 30 months; MITT Population - 42 months
Hide Outcome Measure Data
Hide Analysis Population Description

ITT - The ITT population will consist of all subjects randomized for participation in the study.

MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.

Arm/Group Title Celecoxib Ibuprofen Naproxen
Hide Arm/Group Description:
Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily
Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily
Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Overall Number of Participants Analyzed 8072 8040 7969
Measure Type: Number
Unit of Measure: Percentage of Participants
ITT (N = 8072, 8040, 7969) 0.7 0.9 0.7
MITT (N = 8030, 7990, 7933) 0.3 0.7 0.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments ITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8576
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.67 to 1.40
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments ITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1202
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.53 to 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments ITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1734
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.90 to 1.81
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments MITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0041
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.32 to 0.81
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments MITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.27 to 0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments MITT Population
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4243
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.80 to 1.69
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Patient’s Assessment of Arthritis Pain (VAS)
Hide Description VAS question "How much pain do you have" was graded on a scale from 0 to 100 with 0 indicating "No pain" and 100 indicating "Worst possible pain".
Time Frame ITT and MITT Population - Baseline to 42 months
Hide Outcome Measure Data
Hide Analysis Population Description

ITT - The ITT population will consist of all subjects randomized for participation in the study.

MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.

Arm/Group Title Celecoxib Ibuprofen Naproxen
Hide Arm/Group Description:
Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily
Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily
Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Overall Number of Participants Analyzed 8072 8040 7969
Mean (Standard Deviation)
Unit of Measure: Number of participants
Baseline (ITT) N= 8014, 8001, 7928 54.0  (23.53) 54.1  (23.58) 54.1  (24.04)
Change-Baseline to Mon1 (ITT) N=7382, 7379, 7325 -8.2  (24.69) -9.0  (25.69) -9.9  (25.53)
Change-Baseline to Mon2 (ITT) N=7180, 7090, 7149 -10.5  (26.39) -10.6  (26.92) -11.1  (26.83)
Change-Baseline to Mon4 (ITT) N=6777, 6696, 6740 -11.4  (27.70) -11.7  (28.10) -12.3  (27.80)
Change-Baseline to Mon8 (ITT) N=6230, 6137, 6159 -11.7  (28.92) -12.1  (28.97) -12.1  (28.83)
Change-Baseline to Mon12 (ITT) N=5792, 5696, 5846 -11.0  (29.15) -11.6  (29.29) -11.9  (29.30)
Change-Baseline to Mon18 (ITT) N=5310, 5181. 5246 -11.3  (29.11) -11.3  (29.10) -11.7  (29.33)
Change-Baseline to Mon24 (ITT) N=4818, 4776, 4785 -11.3  (29.44) -11.5  (28.98) -11.4  (29.27)
Change-Baseline to Mon30 (ITT) N=4140, 4069, 4086 -10.5  (29.81) -11.2  (29.71) -11.3  (29.71)
Change-Baseline to Mon36 (ITT) N=3692, 3627, 3635 -10.1  (29.61) -10.7  (29.62) -11.6  (29.80)
Change-Baseline to Mon42 (ITT) N=3469, 3406, 3439 -11.4  (29.78) -11.1  (30.14) -12.1  (30.27)
Baseline (MITT) N=7974, 7954, 7894 54.0  (23.53) 54.1  (23.58) 54.1  (24.02)
Change-Baseline to Mon1 MITT N=7372, 7367, 7321 -8.2  (24.69) -9.0  (25.67) -9.9  (25.53)
Change-Baseline to Mon2 MITT N=7170, 7078, 7142 -10.5  (26.38) -10.6  (26.92) -11.1  (26.84)
Change-Baseline to Mon4 MITT N=6772, 6686, 6732 -11.4  (27.70) -11.7  (28.10) -12.3  (27.81)
Change-Baseline to Mon8 MITT N=6224, 6128, 6155 -11.7  (28.93) -12.1  (28.97) -12.1  (28.84)
Change-Baseline to Mon12 MITT N=5787, 5689, 5844 -11.0  (29.16) -11.6  (29.30) -11.9  (29.30)
Change-Baseline to Mon18 MITT N=5305, 5175, 5242 -11.3  (29.11) -11.3  (29.12) -11.7  (29.33)
Change-Baseline to Mon24 MITT N=4815, 4769, 4782 -11.4  (29.44) -11.5  (29.00) -11.3  (29.26)
Change-Baseline to Mon30 MITT N=4139, 4067, 4085 -10.5  (29.81) -11.2  (29.71) -11.3  (29.70)
Change-Baseline to Mon36 MITT N=3691, 3623, 3635 -10.2  (29.61) -10.7  (29.62) -11.6  (29.80)
Change-Baseline to Mon42 MITT N=3468, 3404, 3438 -11.4  (29.78) -11.1  (30.14) -12.1  (30.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 1 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
1.01 to 2.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 1 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0373
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.05 to 1.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 1 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0129
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.20 to 1.72
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 2 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1830
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.25 to 1.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 2 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7777
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.88 to 0.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 2 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1072
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
-0.14 to 1.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 4 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8237
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
-0.12 to 1.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.40
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 4 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8237
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.88 to 0.70
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.40
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 4 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0587
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
-0.03 to 1.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.40
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 8 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3129
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
-0.39 to 1.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 8 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6526
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.63 to 1.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 8 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5774
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.58 to 1.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 12 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0632
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
-0.04 to 1.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 12 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4540
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
-0.52 to 1.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 12 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2705
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
-0.37 to 1.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 18 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5225
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
-0.58 to 1.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 18 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5996
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-1.10 to 0.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 18 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2461
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
-0.35 to 1.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 24 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8127
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.79 to 1.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.46
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 24 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9641
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.92 to 0.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.46
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 24 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7784
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.77 to 1.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.46
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 30 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2105
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
-0.34 to 1.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.49
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 30 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2909
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
-0.44 to 1.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.49
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 30 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8459
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.86 to 1.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.49
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 36 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1116
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
-0.19 to 1.80
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 36 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9751
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.98 to 1.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 36 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1202
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
-0.21 to 1.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 42 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3767
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
-0.56 to 1.48
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.52
Estimation Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 42 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1123
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.83
Confidence Interval (2-Sided) 95%
-1.85 to 0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.52
Estimation Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 42 (ITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0137
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.26 to 2.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.52
Estimation Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from Baseline to Month 1 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
1.07 to 2.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from Baseline to Month 1 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0197
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.13 to 1.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from Baseline to Month 1 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0094
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.23 to 1.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 2 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1247
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
-0.16 to 1.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 2 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8278
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.81 to 0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 2 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0802
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
-0.08 to 1.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 37 Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 4 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0822
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
-0.09 to 1.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 38 Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 4 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8314
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.86 to 0.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 39 Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 4 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0516
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
-0.01 to 1.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 40 Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 8 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3202
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
-0.40 to 1.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 41 Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 8 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5893
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.60 to 1.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 42 Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 8 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6510
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.63 to 1.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 43 Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 12 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0796
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
-0.09 to 1.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 44 Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 12 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5061
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
-0.57 to 1.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 45 Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 12 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2796
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
-0.38 to 1.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 46 Hide Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 18 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6725
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.69 to 1.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 47 Hide Statistical Analysis 47
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 18 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6381
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-1.10 to 0.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 48 Hide Statistical Analysis 48
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 18 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3737
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
-0.49 to 1.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 49 Hide Statistical Analysis 49
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 24 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9139
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.87 to 0.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 50 Hide Statistical Analysis 50
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 24 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9998
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.92 to 0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 51 Hide Statistical Analysis 51
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 24 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9144
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.88 to 0.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 52 Hide Statistical Analysis 52
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 30 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2250
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
-0.38 to 1.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 53 Hide Statistical Analysis 53
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 30 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2758
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
-0.44 to 1.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 54 Hide Statistical Analysis 54
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 30 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9030
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.94 to 1.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 55 Hide Statistical Analysis 55
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 36 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0910
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
-0.14 to 1.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 56 Hide Statistical Analysis 56
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 36 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7668
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.88 to 1.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 57 Hide Statistical Analysis 57
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 36 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1653
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
-0.31 to 1.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 58 Hide Statistical Analysis 58
Statistical Analysis Overview Comparison Group Selection Celecoxib, Naproxen
Comments Change from baseline to Month 42 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4323
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
-0.65 to 1.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments [Not Specified]
Show Statistical Analysis 59 Hide Statistical Analysis 59
Statistical Analysis Overview Comparison Group Selection Celecoxib, Ibuprofen
Comments Change from baseline to Month 42 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1439
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.81
Confidence Interval (2-Sided) 95%
-1.89 to 0.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments [Not Specified]
Show Statistical Analysis 60 Hide Statistical Analysis 60
Statistical Analysis Overview Comparison Group Selection Ibuprofen, Naproxen
Comments Change from baseline to Month 42 (MITT)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0251
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.16 to 2.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments [Not Specified]
Time Frame Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Celecoxib Ibuprofen Naproxen
Hide Arm/Group Description Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
All-Cause Mortality
Celecoxib Ibuprofen Naproxen
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Celecoxib Ibuprofen Naproxen
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1473/8030 (18.34%)   1624/7992 (20.32%)   1611/7933 (20.31%) 
Blood and lymphatic system disorders       
Anaemia * 1  15/8030 (0.19%)  34/7992 (0.43%)  24/7933 (0.30%) 
Anaemia vitamin B12 deficiency * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Aplastic anaemia * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Coagulopathy * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Haemorrhagic anaemia * 1  2/8030 (0.02%)  1/7992 (0.01%)  2/7933 (0.03%) 
Hypochromic anaemia * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Iron deficiency anaemia * 1  2/8030 (0.02%)  10/7992 (0.13%)  11/7933 (0.14%) 
Leukocytosis * 1  1/8030 (0.01%)  2/7992 (0.03%)  5/7933 (0.06%) 
Leukopenia * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Lymphadenopathy mediastinal * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Microcytic anaemia * 1  0/8030 (0.00%)  0/7992 (0.00%)  3/7933 (0.04%) 
Pancytopenia * 1  2/8030 (0.02%)  0/7992 (0.00%)  2/7933 (0.03%) 
Thrombocytopenia * 1  1/8030 (0.01%)  2/7992 (0.03%)  0/7933 (0.00%) 
Thrombocytosis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Cardiac disorders       
Acute coronary syndrome * 1  7/8030 (0.09%)  7/7992 (0.09%)  3/7933 (0.04%) 
Acute left ventricular failure * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Acute myocardial infarction * 1  22/8030 (0.27%)  20/7992 (0.25%)  18/7933 (0.23%) 
Angina pectoris * 1  13/8030 (0.16%)  11/7992 (0.14%)  13/7933 (0.16%) 
Angina unstable * 1  45/8030 (0.56%)  41/7992 (0.51%)  60/7933 (0.76%) 
Aortic valve disease * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Aortic valve incompetence * 1  0/8030 (0.00%)  2/7992 (0.03%)  3/7933 (0.04%) 
Aortic valve stenosis * 1  3/8030 (0.04%)  1/7992 (0.01%)  2/7933 (0.03%) 
Arrhythmia * 1  1/8030 (0.01%)  7/7992 (0.09%)  3/7933 (0.04%) 
Arrhythmia supraventricular * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Arteriosclerosis coronary artery * 1  5/8030 (0.06%)  5/7992 (0.06%)  7/7933 (0.09%) 
Arteriospasm coronary * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Atrial fibrillation * 1  35/8030 (0.44%)  39/7992 (0.49%)  36/7933 (0.45%) 
Atrial flutter * 1  6/8030 (0.07%)  4/7992 (0.05%)  4/7933 (0.05%) 
Atrioventricular block * 1  1/8030 (0.01%)  3/7992 (0.04%)  0/7933 (0.00%) 
Atrioventricular block complete * 1  1/8030 (0.01%)  7/7992 (0.09%)  2/7933 (0.03%) 
Atrioventricular block second degree * 1  2/8030 (0.02%)  2/7992 (0.03%)  3/7933 (0.04%) 
Atrioventricular dissociation * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Bradyarrhythmia * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Bradycardia * 1  10/8030 (0.12%)  11/7992 (0.14%)  6/7933 (0.08%) 
Bundle branch block left * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Bundle branch block right * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Cardiac aneurysm * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Cardiac arrest * 1  6/8030 (0.07%)  9/7992 (0.11%)  6/7933 (0.08%) 
Cardiac disorder * 1  1/8030 (0.01%)  2/7992 (0.03%)  0/7933 (0.00%) 
Cardiac failure * 1  2/8030 (0.02%)  8/7992 (0.10%)  4/7933 (0.05%) 
Cardiac failure chronic * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Cardiac failure congestive * 1  31/8030 (0.39%)  41/7992 (0.51%)  41/7933 (0.52%) 
Cardiac tamponade * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Cardiac valve disease * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Cardiac ventricular thrombosis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Cardio-respiratory arrest * 1  6/8030 (0.07%)  5/7992 (0.06%)  4/7933 (0.05%) 
Cardiogenic shock * 1  0/8030 (0.00%)  3/7992 (0.04%)  2/7933 (0.03%) 
Cardiomyopathy * 1  3/8030 (0.04%)  4/7992 (0.05%)  2/7933 (0.03%) 
Cardiopulmonary failure * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Cardiovascular disorder * 1  0/8030 (0.00%)  1/7992 (0.01%)  2/7933 (0.03%) 
Congestive cardiomyopathy * 1  1/8030 (0.01%)  1/7992 (0.01%)  1/7933 (0.01%) 
Cor pulmonale chronic * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Coronary artery disease * 1  42/8030 (0.52%)  40/7992 (0.50%)  44/7933 (0.55%) 
Coronary artery insufficiency * 1  1/8030 (0.01%)  2/7992 (0.03%)  1/7933 (0.01%) 
Coronary artery occlusion * 1  9/8030 (0.11%)  8/7992 (0.10%)  8/7933 (0.10%) 
Coronary artery stenosis * 1  4/8030 (0.05%)  9/7992 (0.11%)  6/7933 (0.08%) 
Coronary artery thrombosis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Extrasystoles * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Heart valve incompetence * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Hypertensive cardiomyopathy * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Hypertensive heart disease * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Ischaemic cardiomyopathy * 1  3/8030 (0.04%)  0/7992 (0.00%)  3/7933 (0.04%) 
Left ventricular dysfunction * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Left ventricular failure * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Mitral valve disease * 1  1/8030 (0.01%)  1/7992 (0.01%)  1/7933 (0.01%) 
Mitral valve incompetence * 1  2/8030 (0.02%)  2/7992 (0.03%)  0/7933 (0.00%) 
Myocardial infarction * 1  45/8030 (0.56%)  70/7992 (0.88%)  48/7933 (0.61%) 
Myocardial ischaemia * 1  2/8030 (0.02%)  7/7992 (0.09%)  3/7933 (0.04%) 
Nodal arrhythmia * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Palpitations * 1  2/8030 (0.02%)  3/7992 (0.04%)  4/7933 (0.05%) 
Pericardial effusion * 1  1/8030 (0.01%)  2/7992 (0.03%)  1/7933 (0.01%) 
Pericarditis * 1  0/8030 (0.00%)  1/7992 (0.01%)  4/7933 (0.05%) 
Pleuropericarditis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Postinfarction angina * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Prinzmetal angina * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Silent myocardial infarction * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Sinus bradycardia * 1  0/8030 (0.00%)  3/7992 (0.04%)  3/7933 (0.04%) 
Sinus node dysfunction * 1  2/8030 (0.02%)  3/7992 (0.04%)  4/7933 (0.05%) 
Sinus tachycardia * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Supraventricular extrasystoles * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Supraventricular tachycardia * 1  1/8030 (0.01%)  8/7992 (0.10%)  4/7933 (0.05%) 
Tachyarrhythmia * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Tachycardia * 1  2/8030 (0.02%)  2/7992 (0.03%)  5/7933 (0.06%) 
Tricuspid valve incompetence * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Ventricular extrasystoles * 1  0/8030 (0.00%)  3/7992 (0.04%)  3/7933 (0.04%) 
Ventricular fibrillation * 1  0/8030 (0.00%)  2/7992 (0.03%)  1/7933 (0.01%) 
Ventricular tachycardia * 1  0/8030 (0.00%)  1/7992 (0.01%)  2/7933 (0.03%) 
Bradycardia and atrial flutter with hospitalization cardiorespiratory arrest and ischemia dilated * 1 [1]  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Cardiomyopathy and non-ST elevation MI and atherosclerosis * 1 [1]  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Congenital, familial and genetic disorders       
Arteriovenous malformation * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Atrial septal defect * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Cardiac septal defect * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Cerebrovascular arteriovenous malformation * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Choledochal cyst * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Developmental hip dysplasia * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Diverticulitis Meckel’s * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Haemorrhagic arteriovenous malformation * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Hypertrophic cardiomyopathy * 1  0/8030 (0.00%)  3/7992 (0.04%)  0/7933 (0.00%) 
Renal hypoplasia * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Ear and labyrinth disorders       
Deafness * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Ear discomfort * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Vertigo * 1  5/8030 (0.06%)  2/7992 (0.03%)  8/7933 (0.10%) 
Vertigo positional * 1  0/8030 (0.00%)  3/7992 (0.04%)  3/7933 (0.04%) 
Endocrine disorders       
Adrenal haemorrhage * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Adrenal insufficiency * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Autoimmune thyroiditis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Goitre * 1  2/8030 (0.02%)  4/7992 (0.05%)  0/7933 (0.00%) 
Hyperparathyroidism * 1  3/8030 (0.04%)  4/7992 (0.05%)  0/7933 (0.00%) 
Hyperparathyroidism primary * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Hyperthyroidism * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Hypogonadism * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Hypoparathyroidism * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Inappropriate antidiuretic hormone secretion * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Myxoedema * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Parathyroid disorder * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Thyroid mass * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Eye disorders       
Cataract * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Diplopia * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Eye haemorrhage * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Glaucoma * 1  0/8030 (0.00%)  2/7992 (0.03%)  0/7933 (0.00%) 
Optic neuropathy * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Retinal detachment * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Retinal haemorrhage * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Retinal vein occlusion * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Vision blurred * 1  1/8030 (0.01%)  0/7992 (0.00%)  2/7933 (0.03%) 
Visual impairment * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Vitreous detachment * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastrointestinal disorders       
Abdominal adhesions * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Abdominal discomfort * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Abdominal hernia * 1  5/8030 (0.06%)  4/7992 (0.05%)  7/7933 (0.09%) 
Abdominal incarcerated hernia * 1  3/8030 (0.04%)  0/7992 (0.00%)  2/7933 (0.03%) 
Abdominal pain * 1  14/8030 (0.17%)  7/7992 (0.09%)  13/7933 (0.16%) 
Abdominal pain lower * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Abdominal pain upper * 1  2/8030 (0.02%)  3/7992 (0.04%)  2/7933 (0.03%) 
Abdominal wall haematoma * 1  0/8030 (0.00%)  2/7992 (0.03%)  1/7933 (0.01%) 
Ascites * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Autoimmune pancreatitis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Chronic gastritis * 1  0/8030 (0.00%)  2/7992 (0.03%)  0/7933 (0.00%) 
Colitis * 1  6/8030 (0.07%)  3/7992 (0.04%)  3/7933 (0.04%) 
Colitis ischaemic * 1  1/8030 (0.01%)  4/7992 (0.05%)  4/7933 (0.05%) 
Colitis ulcerative * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Colonic fistula * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Colonic pseudo-obstruction * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Constipation * 1  1/8030 (0.01%)  3/7992 (0.04%)  1/7933 (0.01%) 
Crohn’s disease * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Diarrhoea * 1  3/8030 (0.04%)  8/7992 (0.10%)  5/7933 (0.06%) 
Diarrhoea haemorrhagic * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Diverticular perforation * 1  0/8030 (0.00%)  3/7992 (0.04%)  1/7933 (0.01%) 
Diverticulum * 1  6/8030 (0.07%)  0/7992 (0.00%)  2/7933 (0.03%) 
Diverticulum intestinal * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Diverticulum intestinal haemorrhagic * 1  1/8030 (0.01%)  2/7992 (0.03%)  2/7933 (0.03%) 
Duodenal ulcer * 1  2/8030 (0.02%)  2/7992 (0.03%)  3/7933 (0.04%) 
Duodenal ulcer haemorrhage * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Duodenal ulcer perforation * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Duodenitis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Dysphagia * 1  1/8030 (0.01%)  1/7992 (0.01%)  1/7933 (0.01%) 
Enteritis * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Enterocele * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Enterovesical fistula * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Erosive duodenitis * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Erosive oesophagitis * 1  1/8030 (0.01%)  2/7992 (0.03%)  0/7933 (0.00%) 
Faecaloma * 1  0/8030 (0.00%)  1/7992 (0.01%)  2/7933 (0.03%) 
Femoral hernia * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Food poisoning * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastric perforation * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Gastric ulcer * 1  1/8030 (0.01%)  12/7992 (0.15%)  5/7933 (0.06%) 
Gastric ulcer haemorrhage * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastric varices * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Gastric varices haemorrhage * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Gastric volvulus * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Gastritis * 1  3/8030 (0.04%)  6/7992 (0.08%)  5/7933 (0.06%) 
Gastritis erosive * 1  1/8030 (0.01%)  6/7992 (0.08%)  1/7933 (0.01%) 
Gastritis haemorrhagic * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Gastroduodenal haemorrhage * 1  0/8030 (0.00%)  3/7992 (0.04%)  2/7933 (0.03%) 
Gastroduodenitis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastrointestinal haemorrhage * 1  7/8030 (0.09%)  8/7992 (0.10%)  8/7933 (0.10%) 
Gastrointestinal hypomotility * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Gastrointestinal necrosis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastrointestinal stenosis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastrointestinal ulcer * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Gastrooesophageal reflux disease * 1  1/8030 (0.01%)  3/7992 (0.04%)  4/7933 (0.05%) 
Haematochezia * 1  0/8030 (0.00%)  2/7992 (0.03%)  1/7933 (0.01%) 
Haemorrhoidal haemorrhage * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Haemorrhoids * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Hernial eventration * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Hiatus hernia * 1  2/8030 (0.02%)  2/7992 (0.03%)  2/7933 (0.03%) 
Ileal ulcer * 1  2/8030 (0.02%)  0/7992 (0.00%)  0/7933 (0.00%) 
Ileus * 1  1/8030 (0.01%)  3/7992 (0.04%)  1/7933 (0.01%) 
Ileus paralytic * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Incarcerated inguinal hernia * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Incarcerated umbilical hernia * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Inflammatory bowel disease * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Inguinal hernia * 1  5/8030 (0.06%)  2/7992 (0.03%)  0/7933 (0.00%) 
Intestinal dilatation * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Intestinal ischaemia * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Intestinal obstruction * 1  2/8030 (0.02%)  2/7992 (0.03%)  5/7933 (0.06%) 
Intestinal perforation * 1  0/8030 (0.00%)  0/7992 (0.00%)  3/7933 (0.04%) 
Intestinal ulcer * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Intra-abdominal haemorrhage * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Irritable bowel syndrome * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Large intestinal haemorrhage * 1  4/8030 (0.05%)  3/7992 (0.04%)  0/7933 (0.00%) 
Large intestinal obstruction * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Large intestinal ulcer * 1  1/8030 (0.01%)  2/7992 (0.03%)  2/7933 (0.03%) 
Large intestine perforation * 1  0/8030 (0.00%)  1/7992 (0.01%)  2/7933 (0.03%) 
Large intestine polyp * 1  1/8030 (0.01%)  2/7992 (0.03%)  0/7933 (0.00%) 
Localised intraabdominal fluid collection * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Lower gastrointestinal haemorrhage * 1  2/8030 (0.02%)  3/7992 (0.04%)  3/7933 (0.04%) 
Megacolon * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Melaena * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Mesenteric artery stenosis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Nausea * 1  5/8030 (0.06%)  3/7992 (0.04%)  6/7933 (0.08%) 
Necrotising colitis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Neutropenic colitis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Obstruction gastric * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Oedematous pancreatitis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Oesophageal spasm * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Oesophageal stenosis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Oesophageal ulcer * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Oesophagitis * 1  1/8030 (0.01%)  2/7992 (0.03%)  2/7933 (0.03%) 
Oesophagitis ulcerative * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Pancreatic cyst * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Pancreatic necrosis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Pancreatitis * 1  8/8030 (0.10%)  12/7992 (0.15%)  12/7933 (0.15%) 
Pancreatitis acute * 1  3/8030 (0.04%)  4/7992 (0.05%)  6/7933 (0.08%) 
Pancreatitis chronic * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Pancreatitis necrotising * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Peptic ulcer haemorrhage * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Rectal haemorrhage * 1  4/8030 (0.05%)  4/7992 (0.05%)  2/7933 (0.03%) 
Retroperitoneal haematoma * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Retroperitoneal mass * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Salivary gland calculus * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Small intestinal obstruction * 1  7/8030 (0.09%)  9/7992 (0.11%)  8/7933 (0.10%) 
Umbilical hernia * 1  4/8030 (0.05%)  0/7992 (0.00%)  2/7933 (0.03%) 
Upper gastrointestinal haemorrhage * 1  1/8030 (0.01%)  2/7992 (0.03%)  1/7933 (0.01%) 
Volvulus * 1  0/8030 (0.00%)  3/7992 (0.04%)  0/7933 (0.00%) 
Vomiting * 1  5/8030 (0.06%)  7/7992 (0.09%)  7/7933 (0.09%) 
General disorders       
Adverse drug reaction * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Asthenia * 1  4/8030 (0.05%)  5/7992 (0.06%)  4/7933 (0.05%) 
Cardiac death * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Chest discomfort * 1  2/8030 (0.02%)  5/7992 (0.06%)  4/7933 (0.05%) 
Chest pain * 1  52/8030 (0.65%)  84/7992 (1.05%)  73/7933 (0.92%) 
Complication associated with device * 1  1/8030 (0.01%)  0/7992 (0.00%)  2/7933 (0.03%) 
Cyst rupture * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Death * 1  4/8030 (0.05%)  3/7992 (0.04%)  7/7933 (0.09%) 
Device related thrombosis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Drowning * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Drug interaction * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Electrocution * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Fatigue * 1  2/8030 (0.02%)  2/7992 (0.03%)  2/7933 (0.03%) 
Feeling hot * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
General physical health deterioration * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Generalised oedema * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Granuloma * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Hernia * 1  0/8030 (0.00%)  3/7992 (0.04%)  1/7933 (0.01%) 
Ill-defined disorder * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Impaired healing * 1  1/8030 (0.01%)  1/7992 (0.01%)  2/7933 (0.03%) 
Incarcerated hernia * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Influenza like illness * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Local swelling * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Malaise * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Multiple organ dysfunction syndrome * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Necrosis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Non-cardiac chest pain * 1  23/8030 (0.29%)  19/7992 (0.24%)  23/7933 (0.29%) 
Oedema peripheral * 1  4/8030 (0.05%)  1/7992 (0.01%)  1/7933 (0.01%) 
Organ failure * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Pain * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Pelvic mass * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Peripheral swelling * 1  1/8030 (0.01%)  0/7992 (0.00%)  2/7933 (0.03%) 
Polyp * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Pyrexia * 1  0/8030 (0.00%)  4/7992 (0.05%)  3/7933 (0.04%) 
Sudden cardiac death * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Sudden death * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Surgical failure * 1  0/8030 (0.00%)  1/7992 (0.01%)  2/7933 (0.03%) 
Systemic inflammatory response syndrome * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Vascular stent stenosis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Vascular stent thrombosis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Hepatobiliary disorders       
Acute hepatic failure * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Bile duct obstruction * 1  2/8030 (0.02%)  1/7992 (0.01%)  0/7933 (0.00%) 
Bile duct stone * 1  1/8030 (0.01%)  0/7992 (0.00%)  5/7933 (0.06%) 
Biliary colic * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Biliary dyskinesia * 1  1/8030 (0.01%)  1/7992 (0.01%)  1/7933 (0.01%) 
Biliary tract disorder * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Cholangitis * 1  1/8030 (0.01%)  0/7992 (0.00%)  2/7933 (0.03%) 
Cholecystitis * 1  8/8030 (0.10%)  10/7992 (0.13%)  11/7933 (0.14%) 
Cholecystitis acute * 1  9/8030 (0.11%)  11/7992 (0.14%)  5/7933 (0.06%) 
Cholecystitis chronic * 1  1/8030 (0.01%)  0/7992 (0.00%)  3/7933 (0.04%) 
Cholelithiasis * 1  24/8030 (0.30%)  23/7992 (0.29%)  12/7933 (0.15%) 
Cholestasis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Drug-induced liver injury * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Gallbladder disorder * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Hepatic cyst * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Hepatic failure * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Hepatic function abnormal * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Hepatic lesion * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Hepatic vein thrombosis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Hepatitis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Hepatitis alcoholic * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Jaundice cholestatic * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Jaundice hepatocellular * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Liver disorder * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Portal vein thrombosis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Immune system disorders       
Allergy to arthropod bite * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Anaphylactic reaction * 1  0/8030 (0.00%)  1/7992 (0.01%)  2/7933 (0.03%) 
Anaphylactic shock * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Drug hypersensitivity * 1  0/8030 (0.00%)  0/7992 (0.00%)  3/7933 (0.04%) 
Hypersensitivity * 1  1/8030 (0.01%)  2/7992 (0.03%)  1/7933 (0.01%) 
Sarcoidosis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Infections and infestations       
Abdominal abscess * 1  1/8030 (0.01%)  1/7992 (0.01%)  1/7933 (0.01%) 
Abdominal infection * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Abdominal wall abscess * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Abscess intestinal * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Abscess limb * 1  2/8030 (0.02%)  3/7992 (0.04%)  2/7933 (0.03%) 
Abscess neck * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Acute sinusitis * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Anal abscess * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Appendiceal abscess * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Appendicitis * 1  7/8030 (0.09%)  7/7992 (0.09%)  7/7933 (0.09%) 
Appendicitis perforated * 1  2/8030 (0.02%)  3/7992 (0.04%)  2/7933 (0.03%) 
Arthritis bacterial * 1  5/8030 (0.06%)  2/7992 (0.03%)  2/7933 (0.03%) 
Arthritis infective * 1  0/8030 (0.00%)  2/7992 (0.03%)  3/7933 (0.04%) 
Atypical pneumonia * 1  0/8030 (0.00%)  0/7992 (0.00%)  2/7933 (0.03%) 
Bacteraemia * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Bacterial diarrhoea * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Bacterial disease carrier * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Bacterial infection * 1  1/8030 (0.01%)  2/7992 (0.03%)  0/7933 (0.00%) 
Bacterial sepsis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Beta haemolytic streptococcal infection * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Bone tuberculosis * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Breast abscess * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Bronchitis * 1  10/8030 (0.12%)  16/7992 (0.20%)  17/7933 (0.21%) 
Bronchitis bacterial * 1  1/8030 (0.01%)  1/7992 (0.01%)  0/7933 (0.00%) 
Bursitis infective * 1  2/8030 (0.02%)  0/7992 (0.00%)  1/7933 (0.01%) 
Campylobacter gastroenteritis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Cellulitis * 1  29/8030 (0.36%)  32/7992 (0.40%)  32/7933 (0.40%) 
Cellulitis of male external genital organ * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Cellulitis staphylococcal * 1  1/8030 (0.01%)  1/7992 (0.01%)  2/7933 (0.03%) 
Cholecystitis infective * 1  0/8030 (0.00%)  2/7992 (0.03%)  1/7933 (0.01%) 
Chronic pulmonary histoplasmosis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Chronic sinusitis * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Clostridium difficile colitis * 1  2/8030 (0.02%)  4/7992 (0.05%)  4/7933 (0.05%) 
Clostridium difficile infection * 1  1/8030 (0.01%)  2/7992 (0.03%)  0/7933 (0.00%) 
Cystitis * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Cytomegalovirus infection * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Dengue fever * 1  0/8030 (0.00%)  1/7992 (0.01%)  1/7933 (0.01%) 
Device related infection * 1  1/8030 (0.01%)  4/7992 (0.05%)  3/7933 (0.04%) 
Diabetic foot infection * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Diverticulitis * 1  12/8030 (0.15%)  13/7992 (0.16%)  17/7933 (0.21%) 
Embolic pneumonia * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Empyema * 1  1/8030 (0.01%)  1/7992 (0.01%)  1/7933 (0.01%) 
Encephalitis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Endocarditis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Epididymitis * 1  0/8030 (0.00%)  1/7992 (0.01%)  0/7933 (0.00%) 
Erysipelas * 1  1/8030 (0.01%)  2/7992 (0.03%)  2/7933 (0.03%) 
Escherichia bacteraemia * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
Escherichia infection * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Escherichia sepsis * 1  1/8030 (0.01%)  1/7992 (0.01%)  2/7933 (0.03%) 
Escherichia urinary tract infection * 1  2/8030 (0.02%)  1/7992 (0.01%)  0/7933 (0.00%) 
Extradural abscess * 1  2/8030 (0.02%)  2/7992 (0.03%)  0/7933 (0.00%) 
Gangrene * 1  1/8030 (0.01%)  1/7992 (0.01%)  1/7933 (0.01%) 
Gastroenteritis * 1  12/8030 (0.15%)  21/7992 (0.26%)  7/7933 (0.09%) 
Gastroenteritis bacterial * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastroenteritis viral * 1  4/8030 (0.05%)  4/7992 (0.05%)  3/7933 (0.04%) 
Gastrointestinal infection * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Gastrointestinal viral infection * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%) 
Genitourinary tract infection * 1  0/8030 (0.00%)  0/7992 (0.00%)  1/7933 (0.01%) 
Groin abscess * 1  1/8030 (0.01%)  0/7992 (0.00%)  1/7933 (0.01%) 
H1N1 influenza * 1  1/8030 (0.01%)  0/7992 (0.00%)  0/7933 (0.00%)