Trial Outcomes & Findings for Tadalafil for Pulmonary Hypertension Due to Chronic Lung Disease (NCT NCT01862536)

Results Overview

Change from baseline in distance walked in 6 minutes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

The change in distance walked when assessed at 3 months following trial initiation as compared to baseline, similarly at 6 months compared to baseline, at 9 months compared to baseline and at 12 months compared to baseline.

Results posted on

2021-03-09

Participant Flow

The discrepancy between the enrollment number (44) and number in the participant flow module (36) was due to participant drop out. Of the 44 consented, 3 declined to participate, 3 did not complete the test dose trial, 1 had a medication conflict and 1 died prior to trial initiation.

Participant milestones

Participant milestones
Measure	Placebo Placebo tablet placebo: Daily use in double blind study.	Tadalafil Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
Overall Study STARTED	13	23
Overall Study COMPLETED	10	16
Overall Study NOT COMPLETED	3	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=13 Participants Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=23 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=13 Participants	0 Participants n=23 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=13 Participants	8 Participants n=23 Participants	14 Participants n=36 Participants
Age, Categorical >=65 years	7 Participants n=13 Participants	15 Participants n=23 Participants	22 Participants n=36 Participants
Sex: Female, Male Female	0 Participants n=13 Participants	0 Participants n=23 Participants	0 Participants n=36 Participants
Sex: Female, Male Male	13 Participants n=13 Participants	23 Participants n=23 Participants	36 Participants n=36 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	13 Participants n=13 Participants	23 Participants n=23 Participants	36 Participants n=36 Participants
6 Minute Walk Test	243.50 Meters walked in 6 minutes n=13 Participants	249.35 Meters walked in 6 minutes n=23 Participants	246.425 Meters walked in 6 minutes n=36 Participants

PRIMARY outcome

Timeframe: The change in distance walked when assessed at 3 months following trial initiation as compared to baseline, similarly at 6 months compared to baseline, at 9 months compared to baseline and at 12 months compared to baseline.

Population: .The Overall Number of Participants Analyzed differs with the number in the Participant Flow because of subject drop out over the study period

Change from baseline in distance walked in 6 minutes.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=19 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
Change in 6 Minute Walk Test Change in 6 MWT from baseline to 3 months	7.00 Meters walked in 6 minutes Interval -2.7 to 28.0	16.60 Meters walked in 6 minutes Interval -15.2 to 48.19
Change in 6 Minute Walk Test Change in 6 MWT from baseline to 6 months	16.00 Meters walked in 6 minutes Interval -12.0 to 42.0	4.90 Meters walked in 6 minutes Interval -23.4 to 45.12
Change in 6 Minute Walk Test Change in 6 MWT from baseline to 9 months	-18.00 Meters walked in 6 minutes Interval -61.0 to 32.0	8.93 Meters walked in 6 minutes Interval -24.45 to 54.1
Change in 6 Minute Walk Test Change in 6 MWT from baseline to 12 months	21.00 Meters walked in 6 minutes Interval -9.0 to 40.0	16.76 Meters walked in 6 minutes Interval -1.7 to 49.3

SECONDARY outcome

Timeframe: 12 months

Population: The Overall Number of Participants Analyzed differs with the number in the Participant Flow because of subject drop out and patients who required supplemental oxygen did not have a cardiopulmonary exercise test performed.

Measure of aerobic fitness on exercise assessed by cardiopulmonary exercise test.

Outcome measures

Outcome measures
Measure	Placebo Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=3 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
Maximum VO2	—	13.6 mL/kg/min Interval 10.3 to 15.2

SECONDARY outcome

Timeframe: 6 months

Population: The Overall Number of Participants Analyzed differs with the number in the Participant Flow because these participants refused to have a RHC procedure at the 12 month timepoint and therefore the PVR data was not available for analysis.

Pulmonary vascular resistance assessed on right heart catheterization is a hemodynamic measurement of pulmonary vascular remodeling.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=17 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
Pulmonary Vascular Resistance	4.26 mmHg Interval 2.93 to 5.83	2.69 mmHg Interval 1.87 to 3.7

SECONDARY outcome

Timeframe: 6 months

Population: The Overall Number of Participants Analyzed differs with the number in the Participant Flow because these participants refused to have a RHC procedure at the 12 month timepoint and therefore the mPAP data was not available for analysis.

Mean pulmonary artery pressure assessed by right heart catheterization is a hemodynamic measurement of pulmonary hypertension severity.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=17 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
Mean Pulmonary Artery Pressure	33.00 Wood units Interval 28.0 to 37.5	29.00 Wood units Interval 25.0 to 38.0

SECONDARY outcome

Timeframe: 12 months

Population: The Overall Number of Participants Analyzed differs with the number in the Participant Flow because these participants did not complete an ECHO procedure and therefore TAPSE data was not available for analysis.

The tricuspid annular plane excursion is an echocardiographic measurement of right ventricular systolic dysfunction.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=14 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
Tricuspid Annular Plane Excursion (TAPSE)	2.08 mm Interval 2.0 to 2.45	2.12 mm Interval 1.7 to 2.3

SECONDARY outcome

Timeframe: 12 months

Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. There are 50 items, 2 parts, (3 components). Each item is accorded a weight determined by the degree of distress accorded to each symptom or state described. Scores range from 0-100, with higher scores indicating more limitations

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=16 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
St. George's Respiratory Questionnaire, Dyspnea and Health Related Quality of Life	49.34 score on a scale Interval 43.11 to 61.04	44.64 score on a scale Interval 36.26 to 55.68

SECONDARY outcome

Timeframe: 12 months

Population: The Overall Number of Participants Analyzed differs with the number in the Participant Flow because these participants did not show up for the lab test and therefore the data was not available for analysis.

Plasma BNP concentration is a biochemical marker that correlates positively with pulmonary hypertension severity.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=14 Participants Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
N-type Brain Natriuretic Peptide (BNP) Concentration	37.50 pg/mL Interval 26.0 to 365.2	47.81 pg/mL Interval 17.0 to 98.2

SECONDARY outcome

Timeframe: Early (4 hours and 3 days following treatment) and late (1, 3, 6, 9, 12 months following treatment)

Population: Measurements were not obtained

Changes to resting peripheral oxyhemoglobin saturation levels will be used to assess the safety of the study drug in patients with chronic lung diseases.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: Measurements were not obtained

Changes to peripheral oxyhemoglobin saturation levels on exercise will be used to assess the safety of the study drug in patients with chronic lung diseases.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 0 other events

Deaths: 1 deaths

Tadalafil

Serious events: 4 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=13 participants at risk Placebo tablet placebo: Daily use in double blind study.	Tadalafil n=23 participants at risk Daily use of tadalafil (study drug) at 40 mg orally. Tadalafil: Daily use of study drug to treat pulmonary hypertension.
Respiratory, thoracic and mediastinal disorders COPD exacerbation	30.8% 4/13 • Number of events 4 • 1 year	17.4% 4/23 • Number of events 4 • 1 year
Cardiac disorders chest pain	7.7% 1/13 • Number of events 1 • 1 year	8.7% 2/23 • Number of events 2 • 1 year
Gastrointestinal disorders bowel obstruction	0.00% 0/13 • 1 year	4.3% 1/23 • Number of events 1 • 1 year
Blood and lymphatic system disorders hemoptysis	0.00% 0/13 • 1 year	4.3% 1/23 • Number of events 1 • 1 year
Skin and subcutaneous tissue disorders cellulitis	0.00% 0/13 • 1 year	4.3% 1/23 • Number of events 1 • 1 year
General disorders heartburn, dizziness, inability to swallow	7.7% 1/13 • Number of events 1 • 1 year	17.4% 4/23 • Number of events 5 • 1 year
Eye disorders eye floaters	0.00% 0/13 • 1 year	4.3% 1/23 • Number of events 1 • 1 year

Other adverse events

Adverse event data not reported

Additional Information

Dr. Ronald Goldstein

VA Boston Healthcare System

Phone: 857-203-6578

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place