Pulmonary Hypertension
Conditions
Keywords
Potassium Sparing Diuretics, Right-sided heart failure, Edema
Brief summary
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.
Detailed description
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.
Interventions
DRUGSpironolactone
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.
DRUGPlacebo
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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Body weight \> 40 kg * PAH Diagnostic Group I * Stable subjects with no change in PAH specific therapy within the last 4 weeks * No change in dose of background therapy (digoxin, diuretic) within the last 2 weeks excluding anticoagulation
Exclusion criteria
* Unable to give informed consent * Hemodynamically unstable subjects * Pregnant or breast feeding * Have significant renal insufficiency (serum creatinine \>2.5 mg per deciliter or required hemodialysis) * Have significant liver dysfunction (AST or ALT more than three times upper limit of normal) * Currently on aldosterone receptor blocker (spironolactone or eplerenone) or ACE inhibitor * PH due to left heart disease * Unable or unwilling to comply with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in biomarker levels in the spironolactone treated as compared to placebo treated group. | 16 week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events in patients treated with spironolactone as compared to placebo. | 16 week | 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. | 16 week | — |
| Composite end-point | 16 week | 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. |
Countries
United States
Contacts
Primary ContactZeenat Safdar, MD
Backup ContactGwendolyn Goodloe
Outcome results
None listed