Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension
Verified May 2015 by Baylor College of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Zeenat Safdar, Baylor College of Medicine
First received: November 3, 2011
Last updated: May 6, 2015
Last verified: May 2015
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.
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
||Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| 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.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468571
|Baylor College of Medicine
|Houston, Texas, United States, 77030 |
Baylor College of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
||Zeenat Safdar, MD
||Baylor College of Medicine
||Zeenat Safdar, Associate Professor of Medicine, Baylor College of Medicine
History of Changes
|Other Study ID Numbers:
|Study First Received:
||November 3, 2011
||May 6, 2015
||United States: Institutional Review Board
United States: Food and Drug Administration
Keywords provided by Baylor College of Medicine:
Potassium Sparing Diuretics
Right-sided heart failure
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 28, 2016
Familial Primary Pulmonary Hypertension
Respiratory Tract Diseases
Mineralocorticoid Receptor Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing