Trial Outcomes & Findings for Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis (NCT NCT01214187)
NCT ID: NCT01214187
Last Updated: 2017-06-14
Results Overview
The primary study endpoint was the change in MMP7 serum concentration (ng/ml) from baseline to 12 weeks. Serum MMP7 concentrations in peripheral blood are easily measureable and reflect changes in the alveolar microenvironment. Thus, we have chosen to study mean serum MMP7 concentrations after three months of CO treatment as a surrogate biomarker of the effect of inhaled CO administration on disease progression.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
58 participants
Primary outcome timeframe
Baseline to Week 12
Results posted on
2017-06-14
Participant Flow
The enrollment period opened on 11/29/2011 and was closed on 1/10/2014 when the study reached its enrollment target of 58 subjects. Subjects were enrolled at 8 participating academic medical centers.
Sixty-five subjects were screened, of which 7 subjects were screen failures. Reasons for screen failure included subjects who completed screening changed their mind about participation before visit 2, FEV1/FVC less than 70% predicted, and infection within 1 month before screening. The screening period up to 28 days from date of consent to Visit 2.
Participant milestones
| Measure |
Carbon Monoxide Inhalation
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Overall Study
STARTED
|
29
|
29
|
|
Overall Study
COMPLETED
|
22
|
23
|
|
Overall Study
NOT COMPLETED
|
7
|
6
|
Reasons for withdrawal
| Measure |
Carbon Monoxide Inhalation
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Overall Study
Adverse Event
|
6
|
2
|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
3
|
Baseline Characteristics
Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis
Baseline characteristics by cohort
| Measure |
Carbon Monoxide Inhalation
n=29 Participants
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=29 Participants
Oxygen: Room air oxygen concentrations will be administered as placebo
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.6 years
STANDARD_DEVIATION 6.1 • n=99 Participants
|
68.6 years
STANDARD_DEVIATION 8.4 • n=107 Participants
|
68 years
STANDARD_DEVIATION 7 • n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=99 Participants
|
27 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=99 Participants
|
29 participants
n=107 Participants
|
58 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: One subject randomized to placebo withdrew consent prior to the MMP7 blood draw at visit 2. This is missing data and the reason why we have n=28 for placebo group.
The primary study endpoint was the change in MMP7 serum concentration (ng/ml) from baseline to 12 weeks. Serum MMP7 concentrations in peripheral blood are easily measureable and reflect changes in the alveolar microenvironment. Thus, we have chosen to study mean serum MMP7 concentrations after three months of CO treatment as a surrogate biomarker of the effect of inhaled CO administration on disease progression.
Outcome measures
| Measure |
Carbon Monoxide Inhalation
n=29 Participants
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=28 Participants
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Serum MMP7 Level
|
-0.15 ng/ml
Standard Error 0.58
|
0.88 ng/ml
Standard Error 0.57
|
SECONDARY outcome
Timeframe: Baseline to Week 12Total lung capacity % predicted values (TLC) is a major clinical determinant of restrictive lung disease in practice, with TLC measurement below the 5th percentile of the predicted value indicative of a restrictive ventilatory defect
Outcome measures
| Measure |
Carbon Monoxide Inhalation
n=29 Participants
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=29 Participants
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Total Lung Capacity % Predicted Values (TLC)
|
-2.29 % Predicted
Standard Error 1.12
|
-1.44 % Predicted
Standard Error 1.10
|
SECONDARY outcome
Timeframe: Baseline to Week 12Interstitial changes associated with IPF can worsen diffusing capabilities across the alveolar-capillary membrane. As a result, diffusing capacity of carbon monoxide is an important outcome to assess architectural distortion and resultant decrements in diffusing capabilities
Outcome measures
| Measure |
Carbon Monoxide Inhalation
n=29 Participants
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=29 Participants
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Diffusing Capacity for Carbon Monoxide (DLCO) % Predicted Values
|
1.10 % predicted
Standard Error 1.41
|
0.46 % predicted
Standard Error 1.32
|
SECONDARY outcome
Timeframe: Baseline to Week 12The six minute walk distance is commonly used both in research studies and in clinical practice as a measure of functional capabilities, and changes in six minute walk distance and oxygen use during testing over time often reflect clinically relevant disease progression. We will measure the distance travelled during six minutes (meters) in accordance with published guidelines
Outcome measures
| Measure |
Carbon Monoxide Inhalation
n=29 Participants
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=29 Participants
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Six Minute Walk Distance
|
-35.54 meters
Standard Error 12.83
|
12.92 meters
Standard Error 12.83
|
SECONDARY outcome
Timeframe: Baseline to Week 12St. George's Respiratory Questionnaire (SGRQ) is a validated self-reported instrument. In this instrument, scores range from 0 to 100, with higher scores reflective of worse quality of life.
Outcome measures
| Measure |
Carbon Monoxide Inhalation
n=29 Participants
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=29 Participants
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
St George's Respiratory Questionnaire
|
-2.12 Total Score
Standard Error 1.70
|
-1.55 Total Score
Standard Error 1.72
|
Adverse Events
Carbon Monoxide Inhalation
Serious events: 3 serious events
Other events: 28 other events
Deaths: 0 deaths
Oxygen 21%
Serious events: 7 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Carbon Monoxide Inhalation
n=29 participants at risk
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=29 participants at risk
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
6.9%
2/29 • Number of events 2 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
IPF progression
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
6.9%
2/29 • Number of events 2 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Gastrointestinal disorders
Acute pancreatitis
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
3.4%
1/29 • Number of events 2 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Cardiac disorders
Acute Coronary Syndrome
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Gastrointestinal disorders
Worsening Cirrhosis
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Gastrointestinal disorders
Colonic Obstruction
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute syndrome of innapropriate antidiuretic hormone (SIADH)
|
3.4%
1/29 • Number of events 2 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small Cell Cancer
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Worsening of Shortness of Breath
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Fibrosis Related Death
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
3.4%
1/29 • Number of events 1 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
Other adverse events
| Measure |
Carbon Monoxide Inhalation
n=29 participants at risk
The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
inhaled carbon monoxide: The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.
|
Oxygen 21%
n=29 participants at risk
Oxygen: Room air oxygen concentrations will be administered as placebo
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
17.2%
5/29 • Number of events 5 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
10.3%
3/29 • Number of events 5 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.8%
4/29 • Number of events 4 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
24.1%
7/29 • Number of events 9 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Gastrointestinal disorders
Diarrhea
|
6.9%
2/29 • Number of events 4 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
6.9%
2/29 • Number of events 3 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Nervous system disorders
Dizziness
|
10.3%
3/29 • Number of events 3 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
10.3%
3/29 • Number of events 3 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
48.3%
14/29 • Number of events 16 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
27.6%
8/29 • Number of events 10 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
10.3%
3/29 • Number of events 4 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
6.9%
2/29 • Number of events 3 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
General disorders
Fatigue
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
10.3%
3/29 • Number of events 3 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Nervous system disorders
Headache
|
17.2%
5/29 • Number of events 6 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
27.6%
8/29 • Number of events 9 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
10.3%
3/29 • Number of events 5 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
13.8%
4/29 • Number of events 5 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Infections and infestations
Upper respiratory tract infection
|
10.3%
3/29 • Number of events 4 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
17.2%
5/29 • Number of events 5 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/29 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
6.9%
2/29 • Number of events 3 • Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place