Trial Outcomes & Findings for AntiCoagulant Effectiveness in Idiopathic Pulmonary Fibrosis (NCT NCT00957242)
NCT ID: NCT00957242
Last Updated: 2014-07-23
Results Overview
Death, non-bleeding/non-elective hospitalization, or \>10% drop in forced vital capacity.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
145 participants
Primary outcome timeframe
Events up to 48 weeks
Results posted on
2014-07-23
Participant Flow
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.
Participant milestones
| Measure |
Placebo
Oral placebo (1mg or 2.5mg)
placebo : Oral placebo (1mg or 2.5mg)
|
Warfarin
Oral warfarin titrated to an INR of 2-3
warfarin : Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
|
|---|---|---|
|
Overall Study
STARTED
|
73
|
72
|
|
Overall Study
COMPLETED
|
73
|
72
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
AntiCoagulant Effectiveness in Idiopathic Pulmonary Fibrosis
Baseline characteristics by cohort
| Measure |
Placebo
n=73 Participants
Oral placebo (1mg or 2.5mg)
placebo : Oral placebo (1mg or 2.5mg)
|
Warfarin
n=72 Participants
Oral warfarin titrated to an INR of 2-3
warfarin : Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
|
Total
n=145 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
31 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
53 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
42 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
92 Participants
n=206 Participants
|
|
Age, Continuous
|
66.7 years
STANDARD_DEVIATION 7.4 • n=99 Participants
|
67.3 years
STANDARD_DEVIATION 7.1 • n=107 Participants
|
67 years
STANDARD_DEVIATION 7.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
58 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
106 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
73 participants
n=99 Participants
|
72 participants
n=107 Participants
|
145 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Events up to 48 weeksPopulation: All participants per intention-to-treat (ITT)
Death, non-bleeding/non-elective hospitalization, or \>10% drop in forced vital capacity.
Outcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Death, Non-bleeding/Non-elective Hospitalization, or >10% Drop in Forced Vital Capacity
|
17 events
|
23 events
|
SECONDARY outcome
Timeframe: maximum of 48 weeksPopulation: All participants per intention-to-treat (ITT)
Outcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
All Cause Mortality
|
3 events
|
14 events
|
SECONDARY outcome
Timeframe: 16 weeksWeek-16 change from Baseline
Outcome measures
| Measure |
Placebo
n=44 Participants
matched placebo
|
Warfarin
n=42 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Change in Forced Vital Capacity (FVC) From Baseline to 16 Weeks
|
-0.07 liters
Standard Deviation 0.21
|
-0.01 liters
Standard Deviation 0.17
|
SECONDARY outcome
Timeframe: maximum 48 weeksOutcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
All-cause Hospitalizations
|
11 events
|
20 events
|
SECONDARY outcome
Timeframe: maximum of 48 weeksOutcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Bleeding Events
|
3 events
|
4 events
|
SECONDARY outcome
Timeframe: maximum of 48 weeksOutcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Acute Exacerbations of Idiopathic Pulmonary Fibrosis (IPF)
|
2 events
|
6 events
|
SECONDARY outcome
Timeframe: maximum 48 weeksOutcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Respiratory-related Hospitalizations
|
2 events
|
6 events
|
SECONDARY outcome
Timeframe: maximum of 48 weeksMeasured at 48 Weeks
Outcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Cardiovascular Mortality or Morbidity
|
8 events
|
12 events
|
SECONDARY outcome
Timeframe: Change from baseline to last visit (maximum of 48 weeks)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).
Outcome measures
| Measure |
Placebo
n=73 Participants
matched placebo
|
Warfarin
n=72 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Change in 6-minute Walk Distance (6MWD)
|
-16.41 meters
Standard Deviation 41.31
|
8.68 meters
Standard Deviation 178.91
|
SECONDARY outcome
Timeframe: Week 16 Change from BaselinePopulation: All participants per intention-to-treat
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).
Outcome measures
| Measure |
Placebo
n=41 Participants
matched placebo
|
Warfarin
n=41 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Total Score St. George's Respiratory Questionnaire (SGRQ)
|
1.66 score on a scale
Standard Deviation 11.28
|
3.24 score on a scale
Standard Deviation 12.32
|
SECONDARY outcome
Timeframe: Week 48 / Final VisitThe DLCO measures the partial pressure difference between inspired and expired carbon monoxide.
Outcome measures
| Measure |
Placebo
n=54 Participants
matched placebo
|
Warfarin
n=52 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) From Baseline to 16 Weeks
|
-1.41 mL/min/mmHg
Standard Deviation 2.55
|
-1.34 mL/min/mmHg
Standard Deviation 3.07
|
SECONDARY outcome
Timeframe: maximum of 48 weeksBiomarker that measures biologic activities in patients as opposed to response.
Outcome measures
| Measure |
Placebo
n=35 Participants
matched placebo
|
Warfarin
n=27 Participants
warfarin sodium titrated to an INR of 2.0-3.0
|
|---|---|---|
|
Fibrin D-dimer Change From Baseline to 16 Weeks
|
.02 mg/ml
Standard Deviation 0.20
|
-.61 mg/ml
Standard Deviation 1.26
|
Adverse Events
Placebo
Serious events: 12 serious events
Other events: 28 other events
Deaths: 0 deaths
Warfarin
Serious events: 21 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=73 participants at risk
Oral placebo (1mg or 2.5mg)
placebo : Oral placebo (1mg or 2.5mg)
|
Warfarin
n=72 participants at risk
Oral warfarin titrated to an INR of 2-3
warfarin : Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic Pulmonary Fibrosis
|
8.2%
6/73 • Number of events 6 • 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.
|
13.9%
10/72 • Number of events 10 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.4%
1/73 • Number of events 1 • 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.
|
4.2%
3/72 • Number of events 3 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/73 • 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.
|
2.8%
2/72 • Number of events 3 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Haeamothorax
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumomediastinum
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Hypertension
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Infections and infestations
Pneumonia
|
1.4%
1/73 • Number of events 1 • 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.
|
4.2%
3/72 • Number of events 3 • 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.
|
|
Infections and infestations
Urinary Tract Infection
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Cardiac disorders
Cario-Respiratory Arrest
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Cardiac disorders
Extrasystoles
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Blood and lymphatic system disorders
Anaemia
|
1.4%
1/73 • Number of events 1 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 1 • 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.
|
|
Gastrointestinal disorders
GI Haemorrhage
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/73 • 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.
|
1.4%
1/72 • Number of events 2 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
|
Nervous system disorders
Syncope
|
1.4%
1/73 • Number of events 1 • 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.
|
0.00%
0/72 • 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.
|
Other adverse events
| Measure |
Placebo
n=73 participants at risk
Oral placebo (1mg or 2.5mg)
placebo : Oral placebo (1mg or 2.5mg)
|
Warfarin
n=72 participants at risk
Oral warfarin titrated to an INR of 2-3
warfarin : Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
8.2%
6/73 • Number of events 8 • 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.
|
4.2%
3/72 • Number of events 3 • 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.
|
|
Nervous system disorders
Headache
|
11.0%
8/73 • Number of events 10 • 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.
|
4.2%
3/72 • Number of events 3 • 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.
|
|
Nervous system disorders
Dizziness
|
6.8%
5/73 • Number of events 7 • 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.
|
4.2%
3/72 • Number of events 5 • 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.
|
|
General disorders
Oedema Peripheral
|
6.8%
5/73 • Number of events 5 • 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.
|
2.8%
2/72 • Number of events 2 • 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.
|
|
Injury, poisoning and procedural complications
Contusion
|
5.5%
4/73 • Number of events 7 • 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.
|
6.9%
5/72 • Number of events 7 • 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.
|
Additional Information
Imre Noth, MD, Associate Professor of Medicine
University of Chicago Hospital
Phone: 773-834-1832
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place