Trial Outcomes & Findings for A Pulmonary Arterial Hypertension Study With Macitentan to Validate the PAH-SYMPACT™ in France, Italy and Spain (NCT NCT02081690)
NCT ID: NCT02081690
Last Updated: 2018-03-21
Results Overview
The Cardiopulmonary Symptoms domain consists of 6 items reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms".The symptoms part of the PAH-SYMPACT was administered daily over a 7 day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items. It was administered two times (daily during 7 days each time) prior to administration of Macitentan (Visit 2, Baseline) and daily during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).
TERMINATED
PHASE3
160 participants
From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
2018-03-21
Participant Flow
The study was designed to recruit 160 male and female patients aged 18 to 80 years (inclusive) with PAH. A total of 93 patients were screened and 88 patients were enrolled at 37 recruitment sites. Due to slow recruitment, the sponsor decided to prematurely stop the study.
Participant milestones
| Measure |
Macitentan
Subjects received Macitentan at a 10 mg oral dose, once daily during 16 weeks
|
|---|---|
|
Overall Study
STARTED
|
88
|
|
Overall Study
COMPLETED
|
81
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Macitentan
Subjects received Macitentan at a 10 mg oral dose, once daily during 16 weeks
|
|---|---|
|
Overall Study
Death
|
3
|
|
Overall Study
Physician Decision
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Pulmonary Arterial Hypertension Study With Macitentan to Validate the PAH-SYMPACT™ in France, Italy and Spain
Baseline characteristics by cohort
| Measure |
Macitentan
n=88 Participants
Macitentan tablet, dose of 10 mg, once daily
|
|---|---|
|
Age, Continuous
|
57.5 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)Population: Validation set
The Cardiopulmonary Symptoms domain consists of 6 items reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms".The symptoms part of the PAH-SYMPACT was administered daily over a 7 day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items. It was administered two times (daily during 7 days each time) prior to administration of Macitentan (Visit 2, Baseline) and daily during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).
Outcome measures
| Measure |
Macitentan
n=87 Participants
Macitentan tablet, dose of 10 mg, once daily
|
|---|---|
|
Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT
Cardiopulmonary Symptoms domain score at baseline
|
0.90 Score on a scale
Standard Deviation 0.58
|
|
Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT
Cardiopulmonary Symptoms domain score at week 8
|
0.89 Score on a scale
Standard Deviation 0.63
|
|
Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT
Cardiopulmonary Symptoms domain score at week 16
|
0.89 Score on a scale
Standard Deviation 0.68
|
PRIMARY outcome
Timeframe: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)Population: Validation set
The Cardiovascular Symptoms domain consists of 5 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "no symptoms" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT was administered daily over a 7 day period. The recall period of symptom items is the last 24 hours. An average Cardiovascular Symptoms domain score is determined based on the daily scores of the 5 items. It was administered two times (daily during 7 days each time) prior to administration of Macitentan (Visit 2, Baseline) and daily during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).
Outcome measures
| Measure |
Macitentan
n=87 Participants
Macitentan tablet, dose of 10 mg, once daily
|
|---|---|
|
Evaluation of the Reliability and the Construct Validity of the Cardiovascular Symptoms Domain of the PAH-SYMPACT
Cardiovascular Symptoms domain score at baseline
|
0.58 Score on a scale
Standard Deviation 0.62
|
|
Evaluation of the Reliability and the Construct Validity of the Cardiovascular Symptoms Domain of the PAH-SYMPACT
Cardiovascular Symptoms domain score at week 8
|
0.54 Score on a scale
Standard Deviation 0.62
|
|
Evaluation of the Reliability and the Construct Validity of the Cardiovascular Symptoms Domain of the PAH-SYMPACT
Cardiovascular Symptoms domain score at week 16
|
0.54 Score on a scale
Standard Deviation 0.65
|
PRIMARY outcome
Timeframe: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)Population: Validation set
The Physical Impacts domain consists of 7 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "not at all"/"with no difficulty at all" and value 4 corresponds to "very much"/"extremely"/ "not able at all". The impacts part of the PAH-SYMACT was administered on Day 7 of the symptoms part administration. Items in the impact part have a 7 day recall period. An average Physical Impacts domain score is determined based on the 7 items in the domain. It was administered two times prior to administration of Macitentan (Visit 2, Baseline) and during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).
Outcome measures
| Measure |
Macitentan
n=87 Participants
Macitentan tablet, dose of 10 mg, once daily
|
|---|---|
|
Evaluation of the Reliability and the Construct Validity of the Physical Impacts Domain of the PAH-SYMPACT
Physical Impacts domain score at baseline
|
1.13 Score on a scale
Standard Deviation 0.88
|
|
Evaluation of the Reliability and the Construct Validity of the Physical Impacts Domain of the PAH-SYMPACT
Physical Impacts domain score at week 8
|
1.15 Score on a scale
Standard Deviation 0.97
|
|
Evaluation of the Reliability and the Construct Validity of the Physical Impacts Domain of the PAH-SYMPACT
Physical Impacts domain score at week 16
|
1.25 Score on a scale
Standard Deviation 1.00
|
PRIMARY outcome
Timeframe: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)Population: Validation set
The Cognitive/Emotional Impacts domain consists of 4 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "not at all"/"with no difficulty at all" and value 4 corresponds to "very much"/"extremely"/ "not able at all". The impacts part of the PAH-SYMACT was administered on Day 7 of the symptoms part administration. Items in the impact part have a 7 day recall period. An average Cognitive/Emotional Impacts domain score is determined based on the 4 items in the domain. It was administered two times prior to administration of Macitentan (Visit 2, Baseline) and during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16)."
Outcome measures
| Measure |
Macitentan
n=83 Participants
Macitentan tablet, dose of 10 mg, once daily
|
|---|---|
|
Evaluation of the Reliability and the Construct Validity of the Cognitive/Emotional Impacts Domain of the PAH-SYMPACT
Cogn/Emotional Impacts domain score at baseline
|
0.87 Score on a scale
Standard Deviation 0.77
|
|
Evaluation of the Reliability and the Construct Validity of the Cognitive/Emotional Impacts Domain of the PAH-SYMPACT
Cogn/Emotional Impacts domain score at week 8
|
0.88 Score on a scale
Standard Deviation 0.91
|
|
Evaluation of the Reliability and the Construct Validity of the Cognitive/Emotional Impacts Domain of the PAH-SYMPACT
Cogn/Emotional Impacts domain score at week 16
|
0.91 Score on a scale
Standard Deviation 0.96
|
Adverse Events
Macitentan
Serious adverse events
| Measure |
Macitentan
n=88 participants at risk
Macitentan tablet, dose of 10 mg, once daily
|
|---|---|
|
Vascular disorders
Arteriovenous fistula
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Cardiac disorders
Cardiac arrest
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Cardiac disorders
Cardio-respiratory arrest
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
General disorders
Chest discomfort
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Renal and urinary disorders
Chronic kidney disease
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Cardiac disorders
Coronary artery stenosis
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.4%
3/88 • Number of events 4 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Vascular disorders
Haemorrhage
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Investigations
Investigation
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
General disorders
Oedema peripheral
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Infections and infestations
Pneumonia
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Renal and urinary disorders
Renal failure
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Cardiac disorders
Right ventricular failure
|
4.5%
4/88 • Number of events 5 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Surgical and medical procedures
Sympathectomy
|
1.1%
1/88 • Number of events 1 • From study treatment initiation up to 30 days after study treatment discontinuation
|
Other adverse events
| Measure |
Macitentan
n=88 participants at risk
Macitentan tablet, dose of 10 mg, once daily
|
|---|---|
|
Nervous system disorders
Headache
|
12.5%
11/88 • Number of events 12 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
Vascular disorders
Hypotension
|
5.7%
5/88 • Number of events 6 • From study treatment initiation up to 30 days after study treatment discontinuation
|
|
General disorders
Oedema peripheral
|
9.1%
8/88 • Number of events 8 • From study treatment initiation up to 30 days after study treatment discontinuation
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.
- Publication restrictions are in place
Restriction type: OTHER