Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension
The purpose of this study is to determine the effects of spironolactone on collagen markers in a large number of patients with pulmonary hypertension. In addition, safety and tolerability of spironolactone, an aldosterone receptor antagonist, in patients with pulmonary arterial hypertension, will be determined.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension|
- Change in biomarker levels in the spironolactone treated as compared to placebo treated group. [ Time Frame: 16 week ] [ Designated as safety issue: No ]50 participants will be enrolled in a 16-week study, and each subject will receive placebo or active drug in a random order. At the end of week 8, treatment arm for each subject will be blindly switched. Biomarker levels will be drawn 3 times (baseline, week 8, and week 16) during the study period for each subject.
- Number of adverse events in patients treated with spironolactone as compared to placebo. [ Time Frame: 16 week ] [ Designated as safety issue: Yes ]Safety and tolerability of spironolactone as compared to placebo in PAH.
- Change in six-minute walk distance from baseline to week 8 and week 16. [ Time Frame: 16 week ] [ Designated as safety issue: No ]
- Composite end-point [ Time Frame: 16 week ] [ Designated as safety issue: No ]Composite end-point predefined as greater than 10% increase in walk distance, improvement by at least one functional class and absence of clinical worsening. Clinical worsening will be defined as hospitalization for worsening PAH, all-cause death, addition of prostacyclin therapy, lung transplantation, or atrial septostomy.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Drug: Spironolactone Drug: Placebo
50 mg po daily of spironolactone for 8 weeks. A cross-over study where each subject will receive spironolactone or placebo in a random order for 8 weeks each.
Other Name: Aldactone
Drug: Placebo Drug: Spironolactone
Each subject will receive placebo or spironolactone for 8 weeks. At the end of week 8, treatment arm for each subject will be blindly switched.
So if a study patient received placebo for the first 8 weeks then he/she will be switched to receive active drug (spironolactone) for the next 8 weeks.
Other Name: sugar pill
Pulmonary arterial hypertension (PAH) is an orphan disease characterized by pulmonary artery hypertrophy, and resulting vascular remodeling of involved vessels, often leading to right heart failure. Accumulating evidence from vascular biology, animal models, and therapeutic drug trials suggests significant contributions of the neurohormonal milieu to the disease process, morbidity, and mortality. The renin-angiotensin-aldosterone system (RAAS) is an important neurohormonal pathway that induces collagen synthesis in the myocardium and systemic vasculature. There is paucity of data regarding the contribution of RAAS in the pathogenesis of PAH and the effects of aldosterone blockade in the amelioration of PAH. Thus, the overall goal of this proposal is to investigate the contribution of RAAS to the pathogenesis of PAH, and to explore the effects of an aldosterone blocker, spironolactone, in PAH.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468571
|Contact: Zeenat Safdar, MDemail@example.com|
|Contact: Gwendolyn Goodloefirstname.lastname@example.org|
|United States, Texas|
|Baylor College of Medicine||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Zeenat Safdar, MD||Baylor College of Medicine|