The Acute Effects of the Angiotensin-converting Enzyme Inhibitor Enalaprilat on Flow Distribution

Hypertension Clinical Trial

Official title:

The Acute Effects of the Angiotensin-converting Enzyme Inhibitor Enalaprilat on Flow Distribution After the Bidirectional Cavopulmonary Connection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00741156
• Other study ID #: 1000012255
• Status: Completed
• Phase: Phase 3
• First received: August 25, 2008
• Last updated: November 16, 2015
• Start date: July 2008
• Est. completion date: January 2010

Study information

• Verified date: November 2015
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to study the acute effects of angiotensin-converting enzyme inhibitor (ACEI) on systemic, pulmonary and cerebral blood flow in post bidirectional cavopulmonary connection (BCPC) patients.

Description:

The intermediate stage of the bi-directional cavopulmonary connection (BCPC) in the management algorithm of single ventricle palliation is a unique and extraordinary physiologic condition. It places the superior vena caval blood flow into series with the lungs i.e. pulmonary blood flow is partially dependent on cerebral vascular flow and resistance. Differential reduction in the resistances of the systemic, cerebral and pulmonary vascular beds will result in re-equilibrium of relative blood flows which translate to alterations in arterial oxygen tension and perfusion pressure. This concept is demonstrated by the differential effects of carbon dioxide (CO2) and oxygen (O2). CO2 vasodilates and oxygen (O2) vasoconstricts the cerebral vascular bed; the opposite is true in the lungs. Furthermore, studies have demonstrated that arterial CO2 tension (PaCO2) at hypercarbic levels is favourable to normocarbia in increasing pulmonary, systemic and cerebral blood flows and reducing systemic vascular resistance in acute post BCPC patients.

Administration of angiotensin-converting enzyme inhibitor (ACEI) and other systemic vasodilator drugs are well established for treatment of patients with hypertension and congestive cardiomyopathy in both pediatric and adult populations. Favourable manipulation of the flow to the different vascular beds has been reported in children with significant intra-cardiac shunts in which pulmonary blood flow is decreased relative to the increase in systemic blood flow as a result of reduction of systemic vascular resistance.

Guided by similar principles, ACEI therapy is administered to patients with single ventricle physiology to redistribute relative blood flows across the pulmonary and systemic vascular beds. To date, there exists no study examining the hemodynamic effects of ACEI on relative blood flows in the setting of single ventricle physiology and in particular, no study demonstrates its benefits. The effects of ACEI are unknown on the equilibrium of relative cerebral, systemic and pulmonary blood flows in the post-BCPC state. A relative increase in systemic blood flow, as effected by ACEI, at the expense of cerebral blood flow may potentially adversely decrease pulmonary blood and ultimately reduce arterial oxygen tension. On the other hand, some data suggests that ACEI's improve cerebral autoregulation function; in which drop in blood pressure will signal a vasodilatory response in the cerebral vascular bed which may be particularly advantageous in BCPC patients.

Enalaprilat is the active diacid of the ACEI enalapril maleate. Doses of 0.01 to 0.06 mg/kg i.v. have been safely administered in pediatric studies. Onset of action is 15 minutes and duration of action is up to 12-24 hours. The pharmacokinetics of this drug are ideal for the purpose of this study. In our institution, all patients undergo routine cardiac catheterization after the BCPC procedure for hemodynamic assessment and angiography of cardiac structures to assess for eligibility for the Fontan operation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Months to 5 Years

Eligibility

Inclusion Criteria:

• BCPC patients at time of routine pre-Fontan catheterization

• Patients between the ages of 2 months and 5 years old

Exclusion Criteria:

• Patients who have had ACEI therapy within 24 hours of the procedure

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Congestive Cardiomyopathy
• Hypertension

Intervention

Drug:
• Enalaprilat
Enalaprilat will be administered intravenously i.v. 0.005 - 0.01 mg/kg i.v. over 1 minute

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systemic, Pulmonary and Cerebral Blood Flow at Baseline and After Enalaprilat		Baseline and after enalaprilat	No
Primary	Systemic, Pulmonary and Cerebral Resistance at Baseline and After Enalaprilat	Systemic, pulmonary and cerebral resistance is compared at baseline and after enalaprilat	Baseline and after enalaprilat	No