The Acute Effects of the Angiotensin-Converting Enzyme Inhibitor Enalaprilat on Flow Distribution
Information source: The Hospital for Sick Children
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension; Congestive Cardiomyopathy
Intervention: Enalaprilat (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: The Hospital for Sick Children Official(s) and/or principal investigator(s): Kyong-Jin Lee, MD, Principal Investigator, Affiliation: The Hospital for Sick Children
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.
Clinical Details
Official title: The Acute Effects of the Angiotensin-Converting Enzyme Inhibitor Enalaprilat on Flow Distribution After the Bidirectional Cavopulmonary Connection
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The acute effects of angiotensin-converting enzyme inhibitor (ACEI) on systemic, pulmonary, and cerebral blood flow in post bidirectional cavopulmonary connection (BCPC) patients.
Detailed 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.
Eligibility
Minimum age: 2 Months.
Maximum age: 5 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
The Hospital for Sick Children, Toronto, Ontario, Canada; Recruiting Kyong-Jin Lee, MD, Phone: (416)813-7326, Email: kyong-jin.lee@sickkids.ca Kyong-Jin Lee, MD, Principal Investigator Helen Holtby, MD, Sub-Investigator Lee Benson, MD, Sub-Investigator Rajiv Chaturvedi, MD, Sub-Investigator
Additional Information
Starting date: August 2008
Last updated: August 25, 2008
|