The Assessment of Right Ventricular Contractility in Response to Sildenafil

The Assessment of Right Ventricular Contractility in Response to Sildenafil in Pediatric Patients With Pulmonary Arterial Hypertension

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.

Study Overview

• Status: Terminated
• Conditions: Hypertension
• Intervention / Treatment: Drug: Sildenafil

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Sildenafil; One oral dose of Sildenafil (0.5 mg/kg) will be administered nia a nasogastric tube; Other Names: Viagra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Increase (% change) in endsystolic elastance of the right ventricle from baseline (in comparison to change in endsystolic elastance after inhaled NO)	30 mins after Sildenafil adminsitration

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Andrew Redington, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: August 25, 2008
• First Submitted That Met QC Criteria: August 26, 2008
• First Posted (Estimate): August 27, 2008

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Pediatrics; Pulmonary arterial hypertension; Sildenafil; Catheterization; Right ventricular contractility
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 1000012265