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Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Baylor College of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Zeenat Safdar, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01468571
First received: November 3, 2011
Last updated: February 4, 2013
Last verified: February 2013

November 3, 2011
February 4, 2013
July 2011
July 2015   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01468571 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension
Effects of Spironolactone on Collagen Metabolism in 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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Pulmonary Hypertension
  • Drug: Spironolactone
    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

    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
  • Experimental: Spironolactone
    Drug: Spironolactone Drug: Placebo
    Intervention: Drug: Spironolactone
  • Experimental: Placebo
    Drug: Placebo Drug: Spironolactone
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
December 2015
July 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Zeenat Safdar, MD 713-798-2400 safdar@bcm.edu
Contact: Gwendolyn Goodloe 713-798-2400 gmb@bcm.edu
United States
 
NCT01468571
H24178, K23HL093214
Yes
Zeenat Safdar, Baylor College of Medicine
Baylor College of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Zeenat Safdar, MD Baylor College of Medicine
Baylor College of Medicine
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP