Clinical trial NCT01468571: Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension
Official title: Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pulmonary Hypertension
Keywords: Potassium Sparing Diuretics
Right-sided heart failure
Edema
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-11-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in biomarker levels in the spironolactone treated as compared to placebo treated group.
timeFrame: 16 week
Secondary outcomes:
measure: Number of adverse events in patients treated with spironolactone as compared to placebo.
timeFrame: 16 week
measure: Change in six-minute walk distance from baseline to week 8 and week 16.
timeFrame: 16 week
measure: Composite end-point
timeFrame: 16 week
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Zeenat Safdar, MD
role: PRINCIPAL_INVESTIGATOR
References: