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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00741156
Recruitment Status : Completed
First Posted : August 26, 2008
Results First Posted : December 18, 2015
Last Update Posted : December 18, 2015
Information provided by (Responsible Party):
Kyong-Jin Lee, The Hospital for Sick Children

Brief 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.

Condition or disease Intervention/treatment Phase
Hypertension Congestive Cardiomyopathy Drug: Enalaprilat Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Acute Effects of the Angiotensin-converting Enzyme Inhibitor Enalaprilat on Flow Distribution After the Bidirectional Cavopulmonary Connection
Study Start Date : July 2008
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Arm Intervention/treatment
Experimental: Enalaprilat
enalaprilat 0.005-0.01 mg/kg intravenous x 1 dose
Drug: Enalaprilat
Enalaprilat will be administered intravenously i.v. 0.005 - 0.01 mg/kg i.v. over 1 minute
Other Name: Vasotec

Primary Outcome Measures :
  1. Systemic, Pulmonary and Cerebral Blood Flow at Baseline and After Enalaprilat [ Time Frame: Baseline and after enalaprilat ]
  2. Systemic, Pulmonary and Cerebral Resistance at Baseline and After Enalaprilat [ Time Frame: Baseline and after enalaprilat ]
    Systemic, pulmonary and cerebral resistance is compared at baseline and after enalaprilat

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Months to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00741156

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Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada
Sponsors and Collaborators
The Hospital for Sick Children
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Principal Investigator: Kyong-Jin Lee, MD The Hospital for Sick Children

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Responsible Party: Kyong-Jin Lee, Staff Cardiologist, The Hospital for Sick Children Identifier: NCT00741156    
Other Study ID Numbers: 1000012255
First Posted: August 26, 2008    Key Record Dates
Results First Posted: December 18, 2015
Last Update Posted: December 18, 2015
Last Verified: November 2015
Keywords provided by Kyong-Jin Lee, The Hospital for Sick Children:
congestive cardiomyopathy
angiotensin-converting enzyme inhibitor
cardiac catheterization
Additional relevant MeSH terms:
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Cardiomyopathy, Dilated
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Enzyme Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Antihypertensive Agents