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Trial record 58 of 590 for:    WARFARIN

AntiCoagulant Effectiveness in Idiopathic Pulmonary Fibrosis (ACE-IPF)

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: NCT00957242
Recruitment Status : Terminated (Excess of mortality in the treatment group created safety concerns.)
First Posted : August 12, 2009
Results First Posted : October 21, 2013
Last Update Posted : July 23, 2014
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Duke Clinical Research Institute
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Idiopathic Pulmonary Fibrosis
Interventions Drug: warfarin
Drug: placebo
Enrollment 145
Recruitment Details Subjects were randomized at 25 U.S. sites in a 1:1 ratio to warfarin or matching placebo for a planned treatment period of 48 weeks. International normalized ratios (INR) were monitored using encrypted home point-of-care devices that allowed blinding of study therapy.
Pre-assignment Details  
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description

Oral placebo (1mg or 2.5mg)

placebo : Oral placebo (1mg or 2.5mg)

Oral warfarin titrated to an INR of 2-3

warfarin : Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.

Period Title: Overall Study
Started 73 72
Completed 73 72
Not Completed 0 0
Arm/Group Title Placebo Warfarin Total
Hide Arm/Group Description

Oral placebo (1mg or 2.5mg)

placebo : Oral placebo (1mg or 2.5mg)

Oral warfarin titrated to an INR of 2-3

warfarin : Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.

Total of all reporting groups
Overall Number of Baseline Participants 73 72 145
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 72 participants 145 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
31
  42.5%
22
  30.6%
53
  36.6%
>=65 years
42
  57.5%
50
  69.4%
92
  63.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 73 participants 72 participants 145 participants
66.7  (7.4) 67.3  (7.1) 67  (7.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 72 participants 145 participants
Female
15
  20.5%
24
  33.3%
39
  26.9%
Male
58
  79.5%
48
  66.7%
106
  73.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 73 participants 72 participants 145 participants
73 72 145
1.Primary Outcome
Title Death, Non-bleeding/Non-elective Hospitalization, or >10% Drop in Forced Vital Capacity
Hide Description Death, non-bleeding/non-elective hospitalization, or >10% drop in forced vital capacity.
Time Frame Events up to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants per intention-to-treat (ITT)
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
matched placebo
warfarin sodium titrated to an INR of 2.0-3.0
Overall Number of Participants Analyzed 73 72
Measure Type: Number
Unit of Measure: events
17 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments The study was designed to have 90% power to detect a difference in 48-week event free rates of 70% for the warfarin group versus 50% for the placebo group. A total of at least 95 adjudicated primary endpoints were required to achieve 90% power with 2-sided, type I error rate of 0.05 and a 1:1 randomization ratio. These calculations yielded a requisite total sample size of 256.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27
Comments [Not Specified]
Method Regression, Cox
Comments Prespecified covariates in the model included an indicator variable for the treatment group and the DLCO measurement from the baseline assessment.
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.70 to 2.47
Estimation Comments Warfarin vs. Placebo
2.Secondary Outcome
Title All Cause Mortality
Hide Description [Not Specified]
Time Frame maximum of 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants per intention-to-treat (ITT)
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 73 72
Measure Type: Number
Unit of Measure: events
3 14
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Cox Proportional
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 5.03
Confidence Interval (2-Sided) 95%
1.44 to 17.54
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Forced Vital Capacity (FVC) From Baseline to 16 Weeks
Hide Description Week-16 change from Baseline
Time Frame 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 44 42
Mean (Standard Deviation)
Unit of Measure: liters
-0.07  (0.21) -0.01  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.083
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter t-value
Estimated Value 0.08
Confidence Interval 95%
-0.01 to 0.17
Estimation Comments [Not Specified]
4.Secondary Outcome
Title All-cause Hospitalizations
Hide Description [Not Specified]
Time Frame maximum 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 73 72
Measure Type: Number
Unit of Measure: events
11 20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.054
Comments [Not Specified]
Method Cox Proportional
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.06
Confidence Interval (2-Sided) 95%
0.99 to 4.31
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Bleeding Events
Hide Description [Not Specified]
Time Frame maximum of 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 73 72
Measure Type: Number
Unit of Measure: events
3 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Cox Proportional
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.47
Confidence Interval (2-Sided) 95%
0.64 to 9.56
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Acute Exacerbations of Idiopathic Pulmonary Fibrosis (IPF)
Hide Description [Not Specified]
Time Frame maximum of 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 73 72
Measure Type: Number
Unit of Measure: events
2 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.35
Comments [Not Specified]
Method Cox Proportional
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
0.41 to 12.34
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Respiratory-related Hospitalizations
Hide Description [Not Specified]
Time Frame maximum 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 73 72
Measure Type: Number
Unit of Measure: events
2 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Cox Proportional
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.24
Confidence Interval (2-Sided) 95%
0.65 to 16.10
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Cardiovascular Mortality or Morbidity
Hide Description Measured at 48 Weeks
Time Frame maximum of 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 73 72
Measure Type: Number
Unit of Measure: events
8 12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Cox Proportional
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.24 to 3.39
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change in 6-minute Walk Distance (6MWD)
Hide Description The 6MWD is a measure of exercise tolerance. Change in exercise tolerance is calculated at the latest time point (up to 48 weeks) minus the earliest time point (at baseline).
Time Frame Change from baseline to last visit (maximum of 48 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 73 72
Mean (Standard Deviation)
Unit of Measure: meters
-16.41  (41.31) 8.68  (178.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7222
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter t-value
Estimated Value 10.88
Confidence Interval (2-Sided) 95%
-49.57 to 71.34
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Total Score St. George's Respiratory Questionnaire (SGRQ)
Hide Description The SGRQ is a quality of life measurement used to assess respiratory well being with a 0*-100 range (*indicates better health--lower is better).
Time Frame Week 16 Change from Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
All participants per intention-to-treat
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 41 41
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.66  (11.28) 3.24  (12.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter t-value
Estimated Value -1.78
Confidence Interval (2-Sided) 95%
-7.04 to 3048
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) From Baseline to 16 Weeks
Hide Description The DLCO measures the partial pressure difference between inspired and expired carbon monoxide.
Time Frame Week 48 / Final Visit
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 54 52
Mean (Standard Deviation)
Unit of Measure: mL/min/mmHg
-1.41  (2.55) -1.34  (3.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.957
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter t-value
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-1.67 to 1076
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Fibrin D-dimer Change From Baseline to 16 Weeks
Hide Description Biomarker that measures biologic activities in patients as opposed to response.
Time Frame maximum of 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description:
Oral placebo (1mg or 2.5mg)
Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
Overall Number of Participants Analyzed 35 27
Mean (Standard Deviation)
Unit of Measure: mg/ml
.02  (0.20) -.61  (1.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter t-value
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.84 to -0.12
Estimation Comments [Not Specified]
Time Frame Collected during study participation period plus 4 weeks from last dose of study agent. Maximum of 52 weeks. Mean collection period with study termination was 32 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Warfarin
Hide Arm/Group Description

Oral placebo (1mg or 2.5mg)

placebo : Oral placebo (1mg or 2.5mg)

Oral warfarin titrated to an INR of 2-3

warfarin : Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.

All-Cause Mortality
Placebo Warfarin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/73 (16.44%)      21/72 (29.17%)    
Blood and lymphatic system disorders     
Anaemia * 1  1/73 (1.37%)  1 1/72 (1.39%)  1
Cardiac disorders     
Cario-Respiratory Arrest * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
Cardiomyopathy * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
Extrasystoles * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
Gastrointestinal disorders     
Colitis * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
GI Haemorrhage * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Infections and infestations     
Pneumonia * 1  1/73 (1.37%)  1 3/72 (4.17%)  3
Urinary Tract Infection * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Hyponatraemia * 1  0/73 (0.00%)  0 1/72 (1.39%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder Cancer * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Nervous system disorders     
Syncope * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Idiopathic Pulmonary Fibrosis * 1  6/73 (8.22%)  6 10/72 (13.89%)  10
Dyspnea * 1  1/73 (1.37%)  1 3/72 (4.17%)  3
Respiratory Failure * 1  0/73 (0.00%)  0 2/72 (2.78%)  3
Acute Respiratory Failure * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Aspiration * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Haemoptysis * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
Haeamothorax * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
Hypoxia * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Pneumomediastinum * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
Pulmonary Embolism * 1  1/73 (1.37%)  1 0/72 (0.00%)  0
Pulmonary Hypertension * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
Pneumothorax * 1  0/73 (0.00%)  0 1/72 (1.39%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/73 (38.36%)      16/72 (22.22%)    
Gastrointestinal disorders     
Diarrhoea * 1  6/73 (8.22%)  8 3/72 (4.17%)  3
General disorders     
Oedema Peripheral * 1  5/73 (6.85%)  5 2/72 (2.78%)  2
Injury, poisoning and procedural complications     
Contusion * 1  4/73 (5.48%)  7 5/72 (6.94%)  7
Nervous system disorders     
Headache * 1  8/73 (10.96%)  10 3/72 (4.17%)  3
Dizziness * 1  5/73 (6.85%)  7 3/72 (4.17%)  5
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Imre Noth, MD, Associate Professor of Medicine
Organization: University of Chicago Hospital
Phone: 773-834-1832
EMail: inoth@medicine.bsd.uchicago.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00957242     History of Changes
Other Study ID Numbers: Pro00017156
5U10HL080413-05 ( U.S. NIH Grant/Contract )
671
First Submitted: August 10, 2009
First Posted: August 12, 2009
Results First Submitted: March 4, 2013
Results First Posted: October 21, 2013
Last Update Posted: July 23, 2014