Clinical Trial: Phosphodiesterase-5 Inhibitor in Eisenmenger Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Clinical Efficacy of Phosphodiesterase-5 Inhibitor Tadalafil in Eisenmenger Syndrome - A Randomised, Placebo Controlled, Double Blind, Crossover Study

Brief Summary: A preliminary observational study by the investigators has shown that tadalafil, a selective phosphodiesterase-5 inhibitor (PDE-5) decreases pulmonary vascular resistance(PVR) in patients of eisenmenger syndrome (ES) resulting in increase in pulmonary blood flow (Qp), systemic oxygen saturation (SaO2), functional class and exercise capacity. The aim of this placebo controlled trial was to assess the effect of the drug on exercise capacity and functional class compared to placebo.

Detailed Summary:

Methods Patients of ES with age greater than or equal to 18 years and weight greater than or equal to 30 kgs in World Health Organisation (WHO) functional class II and III attending our congenital clinic were invited to participate in the study. Informed written consent was taken from all the patients before screening procedures were initiated for the study. A detailed clinical examination and non-invasive testing including electrocardiogram, chest X ray, pulmonary function tests (to exclude associated restrictive/obstructive lung disease) and echocardiography(including contrast echo if required for demonstrating right to left shunt) were conducted. Patients with simple congenital heart defects (atrial septal defect > 2cm, ventricular septal defect > 1cm and aortopulmonary communications > 0.4 cm) with echocardiographic evidence of right to left shunt were included. Medical therapy and clinical condition of the patients had to be stable for 3 months prior to screening. Patients on treatment with prostanoids, endothelial receptor antagonists (ERA), PDE-5 inhibitors or any other vasodilators with in 1month prior to screening were excluded. A systemic pulse oximetry (SpO2) between 70% and 90% at rest in room air and a baseline 6 minute walk test(6MWT) distance between 150 and 450 meters were required for inclusion. Eisenmenger physiology was confirmed by cardiac catheterization as mean pulmonary artery pressure > 40mmHg, pulmonary capillary wedge pressure < 15mmHg and pulmonary vascular resistance >10 wood units/m2. Oxygen study was also done in selected patients to diagnose reversible pulmonary arterial hypertension(PAH) and such patients were excluded. Patients were also excluded if they were in WHO class IV, were in congestive heart failure or had PCWP > 15mmHg,had left ventricular ejection fraction <40%, atrial fibrillation, patent ductus arteriosus, complex congenital heart defects, restrictive
Sponsor: Govind Ballabh Pant Hospital

Current Primary Outcome: The primary end point of efficacy was improvement in exercise tolerance as assessed by the un-encouraged 6 minute walk test (6MWT) compared to baseline after 6 weeks of treatment [ Time Frame: 6 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The secondary endpoints were effect of the drug on systemic oxygen saturation (SaO2) [ Time Frame: 6 weeks ]
  • The secondary endpoints were effect of the drug on effective pulmonary blood flow(EPBF) [ Time Frame: 6 weeks ]
  • The secondary endpoints were effect of the drug on pulmonary vascular resistance (PVR). [ Time Frame: 6 weeks ]
  • The secondary endpoints were effect of the drug on systemic vascular resistance (SVR) [ Time Frame: 6 weeks ]
  • The secondary endpoints were effect of the drug on WHO functional class [ Time Frame: 6 weeks ]


Original Secondary Outcome: Same as current

Information By: Govind Ballabh Pant Hospital

Dates:
Date Received: September 8, 2010
Date Started: February 2008
Date Completion:
Last Updated: September 13, 2010
Last Verified: August 2010