The Assessment of Right Ventricular Contractility in Response to Sildenafil

This study has suspended participant recruitment.
(absorption of oral sildenafil not consistent)
Sponsor:
Information provided by (Responsible Party):
Andrew Redington, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00742014
First received: August 25, 2008
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

The primary objective of this study is to examine the effects of Sildenafil, administered during cardiac catheterization, on right ventricular contractility in children with pulmonary arterial hypertension.


Condition Intervention Phase
Hypertension
Drug: Sildenafil
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Assessment of Right Ventricular Contractility in Response to Sildenafil in Pediatric Patients With Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • Increase (% change) in endsystolic elastance of the right ventricle from baseline (in comparison to change in endsystolic elastance after inhaled NO) [ Time Frame: 30 mins after Sildenafil adminsitration ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: August 2008
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Sildenafil
One oral dose of Sildenafil (0.5 mg/kg) will be administered nia a nasogastric tube
Other Name: Viagra

Detailed Description:

The effectiveness of Sildenafil as a pulmonary vasodilator in children with heart disease was first reported in detail during cardiac catheterization and postoperatively in 2003. It is now used frequently for long-term treatment of children with pulmonary arterial hypertension at The Hospital for Sick Children and it is now a routine part of the hospital's testing protocol for all patients being evaluated for pulmonary hypertension in the cardiac catheterization laboratory.

The beneficial effects of Sildenafil in pulmonary hypertension are thought to result predominantly from relative vasodilatory and antiproliferative effects on the pulmonary vasculature. On the basis of early data showing lack of significant PDE5 expression in the normal heart, PDE5 was thought to be expressed in the coronary vessels but not in the human myocardium. Very recently, it was reported for the first time that PDE5 is markedly upregulated in hypertrophied right ventricular myocardium in humans and that in the rat PDE5 inhibition with Sildenafil increases contractility in hypertrophied right ventricular myocardium but not in normal right ventricle, which lacks PDE5 expression. The assessment of right ventricular contractility in humans is a challenge, but we have developed several techniques that are recognized as 'state of the art' assessment of right ventricular function.

The purpose of this study is to examine the effects of Sildenafil, which is routinely administered during cardiac catheterization to assess pulmonary vascular resistance, on right ventricular contractility in children with pulmonary arterial hypertension.

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Significant pulmonary arterial hypertension (mean pulmonary artery pressure > 25 mm Hg)
  • Patients aged 4-18 years
  • Routine cardiac catheterization clinically indicated for deciding therapeutic treatment
  • Informed assent/consent from patient/parent

Exclusion Criteria:

  • Suprasystemic pulmonary artery pressures
  • Evidence of right heart failure
  • History of ventricular arrhythmia
  • Known vascular access arrhythmia
  • Contraindication to Sildenafil
  • Concurrent inotropic / PDE administration
  • Other medical, psychological or social circumstances which complicate a regular participation in the study, and/or increase the risk for the patients themselves
  • No consent/assent
  • Pregnancy or unwillingness to comply with contraceptive advice
  Contacts and Locations
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: NCT00742014

Locations
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Andrew Redington, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Andrew Redington, Head, Heart Centre-Cardiology Division, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00742014     History of Changes
Other Study ID Numbers: 1000012265
Study First Received: August 25, 2008
Last Updated: December 13, 2013
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
Pulmonary arterial hypertension
Pediatrics
Sildenafil
Catheterization
Right ventricular contractility

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on September 18, 2014