Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluate the Effect of Aclidinium Bromide on Long-term Cardiovascular Safety and Exacerbations in Moderate to Very Severe COPD Patients. (ASCENT COPD)

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: NCT01966107
Recruitment Status : Completed
First Posted : October 21, 2013
Results First Posted : December 6, 2018
Last Update Posted : December 6, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions COPD
Chronic Obstructive Pulmonary Disease
Moderate to Very Severe COPD
Interventions Drug: Aclidinium Bromide
Drug: Placebo
Enrollment 3635
Recruitment Details This study was conducted at 522 study centers in North America; 35 centers in Canada and 487 centers in the US. A total of 4000 subjects were planned to be enrolled. A total of 3630 subjects were randomized (1:1) to aclidinium bromide 400 μg twice a day (BID) or placebo BID. Rescue medication (albuterol/salbutamol) was provided for all subjects.
Pre-assignment Details Informed consent form was signed; inclusion/exclusion, smoking status, electrocardiogram, pregnancy test, Pulmonary function testing, Chronic obstructive pulmonary disease (COPD) exacerbation were assessed. Out of 3635 subjects, 5 subjects were duplicated, who, in violation of protocol entrance criteria, entered the study more than once.
Arm/Group Title Aclidinium Bromide Placebo
Hide Arm/Group Description Randomized subjects were administered Aclidinium bromide 400 μg BID, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose dry powder inhalation device (DPI). Subjects on a LAMA (long-acting muscarinic antagonist i.e., inhaled anticholinergics) had to washout 2 weeks prior to randomization. Randomized subjects were administered placebo, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose DPI. Subjects on a LAMA (ie, inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Period Title: Overall Study
Started 1812 1818
Full Analysis Set [1] 1791 1798
Completed [2] 1010 937
Not Completed 802 881
Reason Not Completed
excluded from FAS             21             20
discontinued treatment             345             372
due to study closure             164             186
withdrew from the study             272             303
[1]
Subjects included in full analysis set (FAS)
[2]
Subjects who remained on treatment through this time point
Arm/Group Title Aclidinium Bromide Placebo Total
Hide Arm/Group Description Randomized subjects were administered Aclidinium bromide 400 μg BID, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose dry powder inhalation device (DPI). Subjects on a LAMA (long-acting muscarinic antagonist i.e., inhaled anticholinergics) had to washout 2 weeks prior to randomization. Randomized subjects were administered placebo, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose DPI. Subjects on a LAMA (ie, inhaled anticholinergics) had to washout 2 weeks prior to randomization. Total of all reporting groups
Overall Number of Baseline Participants 1791 1798 3589
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) population consisted of all subjects in the Randomized Population who took at least one dose of the double-blind IP (aclidinium bromide or placebo). Subjects were analyzed according to their randomized treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1791 participants 1798 participants 3589 participants
67.1  (8.5) 67.2  (8.3) 67.2  (8.4)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1791 participants 1798 participants 3589 participants
>=40 - <60 years
340
  19.0%
325
  18.1%
665
  18.5%
>=60 - <70 years
724
  40.4%
725
  40.3%
1449
  40.4%
>=70 years
727
  40.6%
748
  41.6%
1475
  41.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1791 participants 1798 participants 3589 participants
Female
732
  40.9%
752
  41.8%
1484
  41.3%
Male
1059
  59.1%
1046
  58.2%
2105
  58.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1791 participants 1798 participants 3589 participants
American Indian or Alaska Native
5
   0.3%
4
   0.2%
9
   0.3%
Asian
8
   0.4%
4
   0.2%
12
   0.3%
Native Hawaiian or Other Pacific Islander
3
   0.2%
0
   0.0%
3
   0.1%
Black or African American
165
   9.2%
138
   7.7%
303
   8.4%
White
1603
  89.5%
1650
  91.8%
3253
  90.6%
Other
7
   0.4%
2
   0.1%
9
   0.3%
1.Primary Outcome
Title Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Subject Per Year During the First Year of Treatment
Hide Description The rate (number of events per subject per year) of moderate or severe COPD exacerbations during the first year of treatment based on on-treatment analysis with treatment group, baseline inhaled corticosteroids (ICS) use, baseline COPD severity, history of at least 1 exacerbation in the past year, and smoking status as factors and the log of the exposure time adjusted for the time the subjects experienced exacerbations as an offset variable.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population consisted of all subjects in the Randomized Population who took at least one dose of the double-blind IP (aclidinium bromide or placebo). Subjects were analyzed according to their randomized treatment.
Arm/Group Title Aclidinium Bromide Placebo
Hide Arm/Group Description:
Randomized subjects were administered Aclidinium bromide 400 μg BID, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose dry powder inhalation device (DPI). Subjects on a LAMA (long-acting muscarinic antagonist i.e., inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Randomized subjects were administered placebo, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose DPI. Subjects on a LAMA (ie, inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Overall Number of Participants Analyzed 1791 1798
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per subject per year
0.44
(0.40 to 0.50)
0.57
(0.52 to 0.64)
2.Primary Outcome
Title Number of Participants With Major Adverse Cardiovascular Event (MACE) - on Study Analysis
Hide Description To assess the cardiovascular (CV) safety of aclidinium bromide on MACEs. The number of subjects with an adjudicated composite MACE with treatment group, baseline CV severity, and smoking status as factors. MACE for the analyses was defined as any adjudicated event which was a composite of the total of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke (on-study analysis).
Time Frame At Screening, Treatment period (upto 36 months) and Post-treatment follow-up (PTFU)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population consisted of all subjects in the Randomized Population who took at least one dose of the double-blind IP (aclidinium bromide or placebo). Subjects were analyzed according to their randomized treatment.
Arm/Group Title Aclidinium Bromide Placebo
Hide Arm/Group Description:
Randomized subjects were administered Aclidinium bromide 400 μg BID, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose dry powder inhalation device (DPI). Subjects on a LAMA (long-acting muscarinic antagonist i.e., inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Randomized subjects were administered placebo, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose DPI. Subjects on a LAMA (ie, inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Overall Number of Participants Analyzed 1791 1798
Measure Type: Count of Participants
Unit of Measure: Participants
Number of subjects with events
69
   3.9%
76
   4.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aclidinium Bromide, Placebo
Comments Composite MACE
Type of Statistical Test Non-Inferiority
Comments Estimate of the hazard ratio and its 95% CI for comparing aclidinium bromide 400 μg versus placebo were derived using the Cox proportional hazard model. A hazard ratio <1 represents a favorable outcome for aclidinium bromide 400 μg.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.64 to 1.23
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Rate of Hospitalizations Due to COPD Exacerbation Per Subject Per Year During the First Year of Treatment- on Treatment Analysis
Hide Description To assess whether aclidinium bromide reduces moderate or severe COPD exacerbations. The rate of hospitalization (number of events per subject per year) due to COPD exacerbations during the first year of treatment based on on-treatment analysis with treatment group, baseline ICS use, baseline COPD severity, history of at least 1 exacerbation in the past year, and smoking status as factors and the log of the exposure time adjusted for the time the subjects experienced exacerbations as an offset variable.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population consisted of all subjects in the Randomized Population who took at least one dose of the double-blind IP (aclidinium bromide or placebo). Subjects were analyzed according to their randomized treatment.
Arm/Group Title Aclidinium Bromide Placebo
Hide Arm/Group Description:
Randomized subjects were administered Aclidinium bromide 400 μg BID, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose dry powder inhalation device (DPI). Subjects on a LAMA (long-acting muscarinic antagonist i.e., inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Randomized subjects were administered placebo, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose DPI. Subjects on a LAMA (ie, inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Overall Number of Participants Analyzed 1791 1798
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per subject per year
0.07
(0.05 to 0.08)
0.10
(0.08 to 0.13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aclidinium Bromide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Negative Binomial Regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.48 to 0.89
Estimation Comments [Not Specified]
Other Statistical Analysis A rate ratio <1 represents a favorable outcome for aclidinium bromide 400 μg.
4.Secondary Outcome
Title Number of Participants With Major Adverse Cardiovascular Event (MACE) or Other Serious Cardiovascular Events of Interest - On-study Analysis
Hide Description

To assess the CV safety of aclidinium bromide on MACEs. The number of subjects with an adjudicated MACE or other serious CV events of interest with treatment group, baseline CV severity, and smoking status as factors.

Other serious CV events included events from Cardiac tachyarrhythmias plus preferred terms (PTs) Tachycardia, Heart rate increase, and Palpitation; Cardiac failure; Bradycardia and PTs Sinus arrest and Sinus bradycardia; Conduction defects; Conditions associated with Central nervous system haemorrhages and cerebrovascular accidents; and selected PTs included in the Other ischemic heart disease.

Time Frame At Screening, Treatment period (upto 36 months) and Post-treatment follow-up (PTFU)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population consisted of all subjects in the Randomized Population who took at least one dose of the double-blind IP (aclidinium bromide or placebo). Subjects were analyzed according to their randomized treatment.
Arm/Group Title Aclidinium Bromide Placebo
Hide Arm/Group Description:
Randomized subjects were administered Aclidinium bromide 400 μg BID, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose dry powder inhalation device (DPI). Subjects on a LAMA (long-acting muscarinic antagonist i.e., inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Randomized subjects were administered placebo, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose DPI. Subjects on a LAMA (ie, inhaled anticholinergics) had to washout 2 weeks prior to randomization.
Overall Number of Participants Analyzed 1791 1798
Measure Type: Count of Participants
Unit of Measure: Participants
Number of subjects with events
168
   9.4%
160
   8.9%
Time Frame Any adverse event occurring from the time the informed consent form was signed until 15 days after the last dose of study drug were recorded. Adverse events were collected at Visit 1A for subjects who completed a Visit 0.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aclidinium Bromide Placebo
Hide Arm/Group Description Randomized subjects were administered Aclidinium bromide 400 μg BID, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose dry powder inhalation device (DPI). Subjects on a LAMA (long-acting muscarinic antagonist i.e., inhaled anticholinergics) had to washout 2 weeks prior to randomization. Randomized subjects were administered placebo, once in the morning and once in the evening (approximately 12 hours apart), via a multi-dose DPI. Subjects on a LAMA (ie, inhaled anticholinergics) had to washout 2 weeks prior to randomization.
All-Cause Mortality
Aclidinium Bromide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   75/1791 (4.19%)      64/1798 (3.56%)    
Hide Serious Adverse Events
Aclidinium Bromide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   409/1791 (22.84%)      356/1798 (19.80%)    
Blood and lymphatic system disorders     
Iron Deficiency Anaemia * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Anaemia * 1  6/1791 (0.34%)  6 3/1798 (0.17%)  4
Haemorrhagic Anaemia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Microcytic Anaemia * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Anaemia Of Malignant Disease * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  2
Leukocytosis * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Immune Thrombocytopenic Purpura * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Cardiac disorders     
Atrioventricular Block Complete * 1  2/1791 (0.11%)  2 4/1798 (0.22%)  5
Atrioventricular Block Second Degree * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Cardiovascular Disorder * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hypertensive Heart Disease * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Palpitations * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Cardiomyopathy * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Ischaemic Cardiomyopathy * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Stress Cardiomyopathy * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Arteriosclerosis Coronary Artery * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Coronary Artery Disease * 1  21/1791 (1.17%)  22 8/1798 (0.44%)  8
Coronary Artery Occlusion * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Coronary Artery Stenosis * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Cardiac Failure * 1  0/1791 (0.00%)  0 3/1798 (0.17%)  3
Cardiac Failure Acute * 1  6/1791 (0.34%)  6 6/1798 (0.33%)  6
Cardiac Failure Congestive * 1  21/1791 (1.17%)  24 18/1798 (1.00%)  19
Cardiogenic Shock * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Acute Coronary Syndrome * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Acute Myocardial Infarction * 1  14/1791 (0.78%)  14 12/1798 (0.67%)  12
Angina Pectoris * 1  10/1791 (0.56%)  10 9/1798 (0.50%)  9
Angina Unstable * 1  7/1791 (0.39%)  7 1/1798 (0.06%)  1
Myocardial Infarction * 1  10/1791 (0.56%)  10 13/1798 (0.72%)  13
Pericardial Effusion * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Arrhythmia * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Bradycardia * 1  3/1791 (0.17%)  3 2/1798 (0.11%)  2
Tachycardia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Right Ventricular Failure * 1  2/1791 (0.11%)  2 1/1798 (0.06%)  1
Atrial Fibrillation * 1  24/1791 (1.34%)  30 17/1798 (0.95%)  22
Atrial Flutter * 1  4/1791 (0.22%)  4 3/1798 (0.17%)  3
Atrial Tachycardia * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Sinus Node Dysfunction * 1  0/1791 (0.00%)  0 3/1798 (0.17%)  3
Sinus Tachycardia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Supraventricular Tachycardia * 1  1/1791 (0.06%)  1 3/1798 (0.17%)  4
Cardiac Arrest * 1  6/1791 (0.34%)  6 4/1798 (0.22%)  4
Cardio-Respiratory Arrest * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Pulseless Electrical Activity * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Ventricular Arrhythmia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Ventricular Extrasystoles * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Ventricular Tachycardia * 1  3/1791 (0.17%)  3 2/1798 (0.11%)  2
Ear and labyrinth disorders     
Vertigo * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Vertigo Positional * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Eye disorders     
Retinal Aneurysm * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Retinal Artery Occlusion * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Macular Fibrosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Gastrointestinal disorders     
Abdominal Hernia * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Pancreatitis * 1  2/1791 (0.11%)  2 3/1798 (0.17%)  4
Pancreatitis Acute * 1  1/1791 (0.06%)  1 3/1798 (0.17%)  3
Gastrointestinal Polyp Haemorrhage * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Intestinal Polyp * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Colitis * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Colitis Ischaemic * 1  2/1791 (0.11%)  2 1/1798 (0.06%)  1
Enterocolitis Haemorrhagic * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hiatus Hernia * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Diarrhoea * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Diverticulum * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Small Intestinal Obstruction * 1  4/1791 (0.22%)  5 4/1798 (0.22%)  4
Duodenal Ulcer Haemorrhage * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Faecaloma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Gastric Haemorrhage * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Gastric Ulcer Haemorrhage * 1  1/1791 (0.06%)  2 0/1798 (0.00%)  0
Gastritis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Abdominal Pain * 1  6/1791 (0.34%)  6 0/1798 (0.00%)  0
Constipation * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Intestinal Mass * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Intestinal Prolapse * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Enterovesical Fistula * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Barrett's Oesophagus * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Abdominal Discomfort * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Dysphagia * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Oesophageal Food Impaction * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Ileus * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Intestinal Obstruction * 1  3/1791 (0.17%)  3 3/1798 (0.17%)  3
Intestinal Ischaemia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Incarcerated Inguinal Hernia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Rectal Haemorrhage * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Intestinal Perforation * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Large Intestinal Obstruction * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Large Intestinal Stenosis * 1  1/1791 (0.06%)  2 0/1798 (0.00%)  0
Gastrointestinal Haemorrhage * 1  3/1791 (0.17%)  4 4/1798 (0.22%)  4
Haematemesis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Lower Gastrointestinal Haemorrhage * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Melaena * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Upper Gastrointestinal Haemorrhage * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Oesophagitis * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Peptic Ulcer * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Parotid Gland Enlargement * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
General disorders     
Asthenia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Fatigue * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Death * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Sudden Death * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Pyrexia * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Multiple Organ Dysfunction Syndrome * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Systemic Inflammatory Response Syndrome * 1  2/1791 (0.11%)  2 1/1798 (0.06%)  1
Mass * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Oedema Peripheral * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Chest Pain * 1  5/1791 (0.28%)  5 3/1798 (0.17%)  4
Non-Cardiac Chest Pain * 1  17/1791 (0.95%)  19 8/1798 (0.44%)  10
Hepatobiliary disorders     
Cholangitis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Cholangitis Acute * 1  1/1791 (0.06%)  2 0/1798 (0.00%)  0
Cholecystitis * 1  2/1791 (0.11%)  2 1/1798 (0.06%)  1
Cholecystitis Acute * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Cholelithiasis * 1  1/1791 (0.06%)  1 3/1798 (0.17%)  3
Jaundice Cholestatic * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Hepatic Cirrhosis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hepatitis Acute * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Immune system disorders     
Drug Hypersensitivity * 1  3/1791 (0.17%)  3 0/1798 (0.00%)  0
Anaphylactic Reaction * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Anaphylactic Shock * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Infections and infestations     
Appendicitis * 1  5/1791 (0.28%)  5 0/1798 (0.00%)  0
Diverticulitis * 1  1/1791 (0.06%)  1 5/1798 (0.28%)  6
Gastroenteritis * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Infectious Colitis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Arthritis Bacterial * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Bacterial Sepsis * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Breast Cellulitis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Catheter Site Cellulitis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Cellulitis * 1  14/1791 (0.78%)  16 10/1798 (0.56%)  10
Gangrene * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Meningitis Bacterial * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Peritonitis Bacterial * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Pneumonia Bacterial * 1  3/1791 (0.17%)  3 1/1798 (0.06%)  1
Osteomyelitis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Breast Abscess * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Campylobacter Colitis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Extradural Abscess * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Clostridium Difficile Colitis * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Clostridium Difficile Infection * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pseudomembranous Colitis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Tongue Abscess * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Tooth Abscess * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Escherichia Urinary Tract Infection * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Lower Respiratory Tract Infection Fungal * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Herpes Zoster * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Localised Infection * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Post Procedural Infection * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Bacterial Disease Carrier * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
H1n1 Influenza * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Influenza * 1  4/1791 (0.22%)  4 6/1798 (0.33%)  6
Pneumonia Influenzal * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Atypical Pneumonia * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Bronchitis * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Pneumonia * 1  66/1791 (3.69%)  78 58/1798 (3.23%)  61
Muscle Abscess * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Measles * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Bacteraemia * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pulmonary Sepsis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Sepsis * 1  12/1791 (0.67%)  12 14/1798 (0.78%)  14
Septic Shock * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Urosepsis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Staphylococcal Abscess * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Staphylococcal Sepsis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Cellulitis Streptococcal * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pneumonia Pneumococcal * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Pneumonia Streptococcal * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Streptococcal Bacteraemia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Tuberculosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Acute Sinusitis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Cystitis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Pyelonephritis * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Urinary Tract Infection * 1  5/1791 (0.28%)  5 9/1798 (0.50%)  10
Gastroenteritis Viral * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Pneumonia Viral * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Injury, poisoning and procedural complications     
Splenic Rupture * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  3
Coronary Vascular Graft Stenosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Peripheral Arterial Reocclusion * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Subarachnoid Haemorrhage * 1  3/1791 (0.17%)  3 0/1798 (0.00%)  0
Subdural Haematoma * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Open Globe Injury * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Ankle Fracture * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Femoral Neck Fracture * 1  5/1791 (0.28%)  5 3/1798 (0.17%)  3
Femur Fracture * 1  3/1791 (0.17%)  3 1/1798 (0.06%)  1
Fibula Fracture * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Forearm Fracture * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Hip Fracture * 1  5/1791 (0.28%)  5 3/1798 (0.17%)  3
Humerus Fracture * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Lower Limb Fracture * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Patella Fracture * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Radial Head Dislocation * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Radius Fracture * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Tibia Fracture * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Ulna Fracture * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Muscle Strain * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Periprosthetic Fracture * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Nerve Root Injury Lumbar * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Fall * 1  8/1791 (0.45%)  8 3/1798 (0.17%)  3
Fat Embolism * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Road Traffic Accident * 1  6/1791 (0.34%)  6 2/1798 (0.11%)  2
Anaemia Postoperative * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Post Procedural Haematoma * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Post Procedural Haemorrhage * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Intentional Overdose * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Overdose * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pubis Fracture * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Alcohol Poisoning * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Carbon Monoxide Poisoning * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Accidental Overdose * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Osteoradionecrosis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Radiation Dysphagia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Radiation Mucositis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Head Injury * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Laceration * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Cervical Vertebral Fracture * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Fractured Sacrum * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Lumbar Vertebral Fracture * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Spinal Compression Fracture * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Spinal Fracture * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Rib Fracture * 1  4/1791 (0.22%)  4 1/1798 (0.06%)  1
Sternal Fracture * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Investigations     
Electrocardiogram Abnormal * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Heart Rate Decreased * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hepatic Enzyme Increased * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Troponin Increased * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Influenza A Virus Test Positive * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Metabolism and nutrition disorders     
Diabetes Mellitus Inadequate Control * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Diabetic Ketoacidosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Gout * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Electrolyte Imbalance * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hypertriglyceridaemia * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Obesity * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Hyperglycaemia * 1  5/1791 (0.28%)  5 3/1798 (0.17%)  3
Hypoglycaemia * 1  3/1791 (0.17%)  3 6/1798 (0.33%)  7
Lactic Acidosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Acidosis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hypokalaemia * 1  0/1791 (0.00%)  0 3/1798 (0.17%)  4
Hyponatraemia * 1  4/1791 (0.22%)  4 2/1798 (0.11%)  2
Dehydration * 1  4/1791 (0.22%)  4 2/1798 (0.11%)  2
Fluid Overload * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Musculoskeletal and connective tissue disorders     
Bursitis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Hip Deformity * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Intervertebral Disc Degeneration * 1  0/1791 (0.00%)  0 3/1798 (0.17%)  3
Intervertebral Disc Protrusion * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Muscular Weakness * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  3
Back Pain * 1  6/1791 (0.34%)  7 4/1798 (0.22%)  4
Musculoskeletal Chest Pain * 1  4/1791 (0.22%)  5 0/1798 (0.00%)  0
Musculoskeletal Pain * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pain In Extremity * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Osteoarthritis * 1  6/1791 (0.34%)  6 1/1798 (0.06%)  1
Cervical Spinal Stenosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Lumbar Spinal Stenosis * 1  4/1791 (0.22%)  4 1/1798 (0.06%)  1
Spinal Column Stenosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Spondylolisthesis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anal Cancer * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
B-Cell Lymphoma * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Bladder Cancer * 1  2/1791 (0.11%)  2 3/1798 (0.17%)  3
Bladder Transitional Cell Carcinoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Breast Cancer Female * 1  0/1791 (0.00%)  0 4/1798 (0.22%)  4
Invasive Ductal Breast Carcinoma * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Carcinoid Tumour Of The Stomach * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Adenocarcinoma Of Colon * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Colon Cancer * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Dermatofibrosarcoma Protuberans * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Hepatic Cancer * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Hepatic Cancer Metastatic * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Hepatocellular Carcinoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Hepatic Adenoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Hodgkin's Disease * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Laryngeal Cancer * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Benign Salivary Gland Neoplasm * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Squamous Cell Carcinoma Of The Tongue * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Lymphoma * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Meningioma Benign * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Mesothelioma * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Metastases To Central Nervous System * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Adenocarcinoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Metastatic Neoplasm * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Metastatic Squamous Cell Carcinoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Squamous Cell Carcinoma * 1  4/1791 (0.22%)  4 1/1798 (0.06%)  1
Squamous Cell Carcinoma Of Head And Neck * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Non-Hodgkin's Lymphoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Lung Adenocarcinoma * 1  5/1791 (0.28%)  5 2/1798 (0.11%)  2
Lung Adenocarcinoma Stage Iii * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Lung Adenocarcinoma Stage Iv * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Non-Small Cell Lung Cancer * 1  1/1791 (0.06%)  1 6/1798 (0.33%)  6
Non-Small Cell Lung Cancer Stage Iiib * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Squamous Cell Carcinoma Of Lung * 1  6/1791 (0.34%)  6 5/1798 (0.28%)  5
Oesophageal Adenocarcinoma * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Oesophageal Carcinoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Cancer Pain * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pancreatic Carcinoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Prostate Cancer * 1  4/1791 (0.22%)  4 2/1798 (0.11%)  2
Clear Cell Renal Cell Carcinoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Renal Cell Carcinoma * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Lung Neoplasm * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Respiratory Tract Neoplasm * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Lung Cancer Metastatic * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Lung Neoplasm Malignant * 1  6/1791 (0.34%)  6 3/1798 (0.17%)  3
Small Cell Lung Cancer * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Malignant Melanoma * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Basal Cell Carcinoma * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Bowen's Disease * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Transitional Cell Carcinoma * 1  2/1791 (0.11%)  2 1/1798 (0.06%)  1
Vaginal Cancer Stage 0 * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Nervous system disorders     
Basal Ganglia Haemorrhage * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Carotid Artery Occlusion * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Cerebral Haemorrhage * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Cerebral Infarction * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Cerebrovascular Accident * 1  9/1791 (0.50%)  9 4/1798 (0.22%)  4
Embolic Stroke * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Haemorrhage Intracranial * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Ischaemic Stroke * 1  1/1791 (0.06%)  1 5/1798 (0.28%)  5
Lacunar Infarction * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Carotid Artery Disease * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Carotid Artery Stenosis * 1  4/1791 (0.22%)  4 5/1798 (0.28%)  6
Balance Disorder * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Syncope * 1  7/1791 (0.39%)  7 2/1798 (0.11%)  2
Encephalopathy * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Toxic Encephalopathy * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Generalised Tonic-Clonic Seizure * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Tension Headache * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Lumbar Radiculopathy * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Sciatica * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hemianopia Homonymous * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Dizziness * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Presyncope * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Paraesthesia * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Paraplegia * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Neuropathy Peripheral * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Seizure * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  4
Radicular Pain * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Radiculopathy * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Spinal Claudication * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Transient Ischaemic Attack * 1  8/1791 (0.45%)  9 5/1798 (0.28%)  5
Product Issues     
Device Malfunction * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Psychiatric disorders     
Anxiety * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Confusional State * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Delirium * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Depression * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Major Depression * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Mental Status Changes * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Alcohol Abuse * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Drug Use Disorder * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Substance Use Disorder * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Renal and urinary disorders     
Pollakiuria * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Urinary Retention * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Bladder Diverticulum * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Bladder Necrosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Renal Mass * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Acute Kidney Injury * 1  7/1791 (0.39%)  7 7/1798 (0.39%)  7
Chronic Kidney Disease * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Renal Failure * 1  5/1791 (0.28%)  5 0/1798 (0.00%)  0
Renal Impairment * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Nephrolithiasis * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Hydronephrosis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Renal Artery Thrombosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Haematuria * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Proteinuria * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Reproductive system and breast disorders     
Breast Mass * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Prostatomegaly * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Pickwickian Syndrome * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Respiratory Arrest * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Respiratory Distress * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Sleep Apnoea Syndrome * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Asthma * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Chronic Obstructive Pulmonary Disease * 1  1/1791 (0.06%)  1 3/1798 (0.17%)  3
Hypercapnia * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Hypoxia * 1  4/1791 (0.22%)  5 1/1798 (0.06%)  1
Respiratory Acidosis * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Haemoptysis * 1  0/1791 (0.00%)  0 3/1798 (0.17%)  3
Pneumonitis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pulmonary Fibrosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Bronchopleural Fistula * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pleurisy * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Haemothorax * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Pleural Effusion * 1  4/1791 (0.22%)  4 2/1798 (0.11%)  3
Pneumothorax * 1  3/1791 (0.17%)  3 5/1798 (0.28%)  5
Pneumothorax Spontaneous * 1  3/1791 (0.17%)  3 3/1798 (0.17%)  4
Pulmonary Hypertension * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Acute Pulmonary Oedema * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Pulmonary Oedema * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Pulmonary Embolism * 1  4/1791 (0.22%)  4 4/1798 (0.22%)  4
Acute Respiratory Failure * 1  16/1791 (0.89%)  20 17/1798 (0.95%)  18
Chronic Respiratory Failure * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Respiratory Failure * 1  9/1791 (0.50%)  9 11/1798 (0.61%)  13
Pulmonary Mass * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Thoracic Haemorrhage * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Skin and subcutaneous tissue disorders     
Angioedema * 1  1/1791 (0.06%)  1 2/1798 (0.11%)  2
Stasis Dermatitis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Erythema * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Subcutaneous Emphysema * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Skin Ulcer * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Vascular disorders     
Accelerated Hypertension * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Hypertensive Crisis * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Aortic Aneurysm * 1  4/1791 (0.22%)  4 2/1798 (0.11%)  2
Aortic Aneurysm Rupture * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Aortic Occlusion * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Aortic Stenosis * 1  2/1791 (0.11%)  2 2/1798 (0.11%)  2
Leriche Syndrome * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Hypovolaemic Shock * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Shock * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Haematoma * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Thrombosis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Arteriosclerosis * 1  0/1791 (0.00%)  0 1/1798 (0.06%)  1
Peripheral Venous Disease * 1  2/1791 (0.11%)  2 0/1798 (0.00%)  0
Peripheral Artery Aneurysm * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Deep Vein Thrombosis * 1  5/1791 (0.28%)  5 2/1798 (0.11%)  2
Pelvic Venous Thrombosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Thrombophlebitis Superficial * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Peripheral Vascular Disorder * 1  3/1791 (0.17%)  4 2/1798 (0.11%)  2
Intermittent Claudication * 1  2/1791 (0.11%)  2 1/1798 (0.06%)  4
Peripheral Arterial Occlusive Disease * 1  3/1791 (0.17%)  5 3/1798 (0.17%)  3
Peripheral Artery Occlusion * 1  0/1791 (0.00%)  0 2/1798 (0.11%)  2
Peripheral Ischaemia * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  3
Hypertension * 1  3/1791 (0.17%)  3 2/1798 (0.11%)  2
Hypotension * 1  8/1791 (0.45%)  8 1/1798 (0.06%)  1
Orthostatic Hypotension * 1  1/1791 (0.06%)  1 1/1798 (0.06%)  1
Arteriovenous Fistula * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
Vena Cava Thrombosis * 1  1/1791 (0.06%)  1 0/1798 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0 and 18.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Aclidinium Bromide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1105/1791 (61.70%)      1065/1798 (59.23%)    
Blood and lymphatic system disorders     
Anaemia * 2  40/1791 (2.23%)  40 38/1798 (2.11%)  39
Cardiac disorders     
Atrial Fibrillation * 2  27/1791 (1.51%)  30 40/1798 (2.22%)  44
Gastrointestinal disorders     
Diarrhoea * 2  58/1791 (3.24%)  62 62/1798 (3.45%)  67
Constipation * 2  60/1791 (3.35%)  65 53/1798 (2.95%)  53
Gastrooesophageal Reflux Disease * 2  38/1791 (2.12%)  38 23/1798 (1.28%)  23
Nausea * 2  77/1791 (4.30%)  83 57/1798 (3.17%)  64
General disorders     
Oedema Peripheral * 2  48/1791 (2.68%)  54 61/1798 (3.39%)  70
Infections and infestations     
Bronchitis * 1  70/1791 (3.91%)  85 74/1798 (4.12%)  92
Pneumonia * 2  46/1791 (2.57%)  51 52/1798 (2.89%)  57
Sinusitis * 2  65/1791 (3.63%)  87 63/1798 (3.50%)  73
Upper Respiratory Tract Infection * 2  86/1791 (4.80%)  104 101/1798 (5.62%)  117
Urinary Tract Infection * 2  90/1791 (5.03%)  122 84/1798 (4.67%)  104
Viral Upper Respiratory Tract Infection * 2  78/1791 (4.36%)  95 67/1798 (3.73%)  77
Musculoskeletal and connective tissue disorders     
Arthralgia * 2  50/1791 (2.79%)  53 45/1798 (2.50%)  51
Muscle Spasms * 2  40/1791 (2.23%)  44 34/1798 (1.89%)  36
Back Pain * 2  69/1791 (3.85%)  72 54/1798 (3.00%)  57
Musculoskeletal Pain * 2  28/1791 (1.56%)  31 38/1798 (2.11%)  40
Pain In Extremity * 2  35/1791 (1.95%)  37 38/1798 (2.11%)  41
Nervous system disorders     
Headache * 2  57/1791 (3.18%)  74 65/1798 (3.62%)  84
Dizziness * 2  44/1791 (2.46%)  46 42/1798 (2.34%)  45
Psychiatric disorders     
Anxiety * 2  34/1791 (1.90%)  35 39/1798 (2.17%)  42
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 2  48/1791 (2.68%)  52 70/1798 (3.89%)  74
Cough * 2  67/1791 (3.74%)  71 62/1798 (3.45%)  66
Vascular disorders     
Hypertension * 2  64/1791 (3.57%)  66 56/1798 (3.11%)  60
1
Term from vocabulary, Bronchitis
2
Term from vocabulary, MedDRA 20.0 and 18.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
This submission /document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: AstraZeneca Clinical
Organization: Study Information Center
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01966107    
Other Study ID Numbers: D6560C00002
LAS-MD-45 ( Other Identifier: Forest Research )
First Submitted: October 16, 2013
First Posted: October 21, 2013
Results First Submitted: September 19, 2018
Results First Posted: December 6, 2018
Last Update Posted: December 6, 2018