Clinical trial NCT00742014: The Assessment of Right Ventricular Contractility in Response to Sildenafil
Official title: The Assessment of Right Ventricular Contractility in Response to Sildenafil in Pediatric Patients With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypertension
Keywords: Pulmonary arterial hypertension
Pediatrics
Sildenafil
Catheterization
Right ventricular contractility
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2008-08-27
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Increase (% change) in endsystolic elastance of the right ventricle from baseline (in comparison to change in endsystolic elastance after inhaled NO)
timeFrame: 30 mins after Sildenafil adminsitration
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Andrew Redington, MD
role: PRINCIPAL_INVESTIGATOR
References: