Trial Outcomes & Findings for Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan (NCT NCT01051960)

NCT ID: NCT01051960

Last Updated: 2020-11-02

Results Overview

We defined ePH (exercise PH) as an mPAP of 30 mmHg, PCWP of 18 mm Hg, and a transpulmonary gradient (TPG) of 15 mm Hg, where TPG equals mPAP minus PCWP. We defined ePVH (exercise pulmonary venous hypertension) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg. We defined eoPH (exercise out of proportion) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg (4). Our hypothesis was that SSc patients with normal exercise physiology and ePVH have a different patho-physiology compared to patients with pulmonary vascular disease (ePH and eoPH).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 12 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2020-11-02

Participant Flow

15 participants were screened, and 12 were eligible and enrolled in the study

Participant milestones

Measure	Ambrisentan ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Overall Study STARTED	12
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Ambrisentan ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Overall Study Adverse Event	1

Baseline Characteristics

Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan

Baseline characteristics by cohort

Measure	Ambrisentan n=12 Participants ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Age, Continuous	47.6 years STANDARD_DEVIATION 19.4 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

We defined ePH (exercise PH) as an mPAP of 30 mmHg, PCWP of 18 mm Hg, and a transpulmonary gradient (TPG) of 15 mm Hg, where TPG equals mPAP minus PCWP. We defined ePVH (exercise pulmonary venous hypertension) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg. We defined eoPH (exercise out of proportion) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg (4). Our hypothesis was that SSc patients with normal exercise physiology and ePVH have a different patho-physiology compared to patients with pulmonary vascular disease (ePH and eoPH).

Outcome measures

Measure	Ambrisentan n=11 Participants ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24	37.4 mmHg Standard Deviation 8.3

SECONDARY outcome

Timeframe: 24 weeks

ATS guideline based assessment with known minimally clinically important difference

Outcome measures

Measure	Ambrisentan n=11 Participants ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Change in Distance Walked in Six Minutes From Baseline to 24 Week	44.5 meters Standard Deviation 10.3

SECONDARY outcome

Timeframe: 24 weeks

Number of participants exceeding minimally important difference estimates on changes in quality of life as assessed by SF-36 (short form 36) quality of life index with mental and physical component scores, or by HAQ-DI (health assessment questionnaire disability index) limitations that may be related to musculoskeletal limitations

Outcome measures

Measure	Ambrisentan n=11 Participants ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Quality of Life (QOL) Based on SF36 and HAQ-DI	0 Participants

SECONDARY outcome

Timeframe: 24 weeks

Assessing limitations that may be related to musculoskeletal limitations, the HAQ-DI assesses the difficulty a participant has had in the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items in which level of difficulty is scored from 0 to 3 with 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. The 8 domain scores are averaged into a total HAQ-DI score ranging from 0 (no disability) to 3 (completely disabled).

Outcome measures

Measure	Ambrisentan n=12 Participants ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
HAQ-DI (Health Assessment Questionnaire Disability Index)	1.12 score on a scale Standard Deviation 0.02

SECONDARY outcome

Timeframe: 24 weeks

To assess overall health, daily life, and perceived well-being in patients with underlying lung disease, the SGRQ is a health-related quality of life questionnaire divided into 3 components : symptoms, activity and impact. The total score (summed weights) can range from 0 to 100 with a lower score denoting a better health status.

Outcome measures

Measure	Ambrisentan n=12 Participants ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
St. George's Respiratory Questionnaire	13.2 score on a scale Standard Deviation 11.7

Adverse Events

Ambrisentan

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ambrisentan n=12 participants at risk ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Blood and lymphatic system disorders edema	8.3% 1/12 • Number of events 1 • 24 weeks

Other adverse events

Measure	Ambrisentan n=12 participants at risk ambrisentan dosed at either 5mg or 10mg orally once per day Ambrisentan: Ambrisentan 5mg or 10mg once daily
Respiratory, thoracic and mediastinal disorders Upper respiratory symptoms	16.7% 2/12 • Number of events 2 • 24 weeks
Respiratory, thoracic and mediastinal disorders Nasal Congestion	41.7% 5/12 • Number of events 5 • 24 weeks
Gastrointestinal disorders Constipation	8.3% 1/12 • Number of events 1 • 24 weeks
General disorders Joint and body pain	8.3% 1/12 • Number of events 1 • 24 weeks
Hepatobiliary disorders Elevated liver function tests	8.3% 1/12 • Number of events 1 • 24 weeks
Blood and lymphatic system disorders Edema	41.7% 5/12 • Number of events 5 • 24 weeks
General disorders Headache	8.3% 1/12 • Number of events 1 • 24 weeks
Skin and subcutaneous tissue disorders Tinea Corporis	8.3% 1/12 • Number of events 1 • 24 weeks
Immune system disorders Allergic reaction	8.3% 1/12 • Number of events 1 • 24 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchoalveolar carcinoma	8.3% 1/12 • Number of events 1 • 24 weeks
Gastrointestinal disorders Fecal incontinence	8.3% 1/12 • Number of events 1 • 24 weeks
Musculoskeletal and connective tissue disorders Pulled muscle	8.3% 1/12 • Number of events 1 • 24 weeks

Additional Information

Rajan Saggar, MD

University of California, Los Angeles

Phone: (310) 794-9718

Email: rsaggar@mednet.ucla.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place