A Phase 4 interventional study of Ambrisentan in Systemic Sclerosis, Shortness of Breath and Pulmonary Hypertension, sponsored by University of California, Los Angeles. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2020-11-02.
Sponsored by University of California, Los Angeles · Phase 4, Interventional, and Treatment
The purpose of this study is to determine the clinical characteristics and hemodynamic profiles that predict exercise induced pulmonary hypertension in 15 patients with systemic sclerosis. The study also aims to determine the effectiveness of Ambrisentan for subjects with exercise induced Pulmonary Arterial Hypertension (PAH) with scleroderma
The current literature addresses therapies for patients with resting PAH only, diagnosed by right heart catheterization. However, the World Health Organization (WHO) also recognizes and defines exercise induced pulmonary arterial hypertension (ex-PAH), which may precede the development of resting PAH. The natural progression of PAH, especially during exercise, has not been well delineated. An exercise hemodynamic study previously showed that in normal healthy subjects the mean pulmonary pressure does not exceed 30mmHg even at maximal cardiac outputs. A prior study evaluated exercise Doppler echocardiography systemic sclerosis patients with normal resting echocardiograms, finding an abnormal response which was defined as an estimated right ventricular systolic pressure greater than 40 mmHg. In the same study, 6.6% of the patients progressed to resting PAH over the followup period of 12 months. Limited data is available regarding the prevalence of ex-PAH in systemic sclerosis using right heart catheterization.
1,105 studies on the registry are indexed under Hypertension, Pulmonary; 234 are open to participants now.
This study's enrollment of 12 is below the median of 35 across 649 interventional studies indexed under Hypertension, Pulmonary.
Browse Hypertension, Pulmonary studies →University of California, Los Angeles is the lead sponsor of 1,142 studies on the registry; 192 are open to participants now.
Of its 91 completed or terminated interventional studies of FDA-regulated products, 66 (73%) have results posted.
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Systemic Sclerosis diagnosed by the American College of Rheumatology consensus statement including any of the following:
Exclusion Criteria:
ambrisentan dosed at either 5mg or 10mg orally once per day
Drug: Ambrisentan
Ambrisentan 5mg or 10mg once daily
Also known as: Letairis
Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24
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).
Time frame: 24 weeks
Change in Distance Walked in Six Minutes From Baseline to 24 Week
ATS guideline based assessment with known minimally clinically important difference
Time frame: 24 weeks
Quality of Life (QOL) Based on SF36 and HAQ-DI
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
Time frame: 24 weeks
HAQ-DI (Health Assessment Questionnaire Disability Index)
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).
Time frame: 24 weeks
St. George's Respiratory Questionnaire
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.
Time frame: 24 weeks
15 participants were screened, and 12 were eligible and enrolled in the study
| Milestone | Ambrisentan |
|---|---|
| Started | 12 |
| Completed | 11 |
| Not completed | 1 |
| Withdrew: Adverse event | 1 |
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).
| mmHg | Ambrisentan |
|---|---|
| Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24 | 37.4 ± 8.3 |
ATS guideline based assessment with known minimally clinically important difference
| meters | Ambrisentan |
|---|---|
| Change in Distance Walked in Six Minutes From Baseline to 24 Week | 44.5 ± 10.3 |
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
| Participants | Ambrisentan |
|---|---|
| Quality of Life (QOL) Based on SF36 and HAQ-DI | 0 |
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).
| score on a scale | Ambrisentan |
|---|---|
| HAQ-DI (Health Assessment Questionnaire Disability Index) | 1.12 ± 0.02 |
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.
| score on a scale | Ambrisentan |
|---|---|
| St. George's Respiratory Questionnaire | 13.2 ± 11.7 |
Collected over 24 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ambrisentan | 0/12 (0%) | 1/12 (8.3%) | 12/12 (100%) |
| Event | Ambrisentan |
|---|---|
| edemaBlood and lymphatic system disorders | 1/12 |
| Event | Ambrisentan |
|---|---|
| Nasal CongestionRespiratory, thoracic and mediastinal disorders | 5/12 |
| EdemaBlood and lymphatic system disorders | 5/12 |
| Upper respiratory symptomsRespiratory, thoracic and mediastinal disorders | 2/12 |
| ConstipationGastrointestinal disorders | 1/12 |
| Joint and body painGeneral disorders | 1/12 |
| Elevated liver function testsHepatobiliary disorders | 1/12 |
| HeadacheGeneral disorders | 1/12 |
| Tinea CorporisSkin and subcutaneous tissue disorders | 1/12 |
| Allergic reactionImmune system disorders | 1/12 |
| Bronchoalveolar carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/12 |
| Age, Continuous(years) | Ambrisentan |
|---|---|
| Mean | 47.6 ± 19.4 |
| Sex: Female, Male(Participants) | Ambrisentan |
|---|---|
| Female | 11 |
| Male | 1 |
| Region of Enrollment(participants) | Ambrisentan |
|---|---|
| United States | 12 |
Plan to share: No
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University of California, Los Angeles