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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2008 by The Hospital for Sick Children.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00741156
First received: August 25, 2008
Last updated: NA
Last verified: August 2008
History: No changes posted
  Purpose

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 Intervention Phase
Hypertension
Congestive Cardiomyopathy
Drug: Enalaprilat
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • The acute effects of angiotensin-converting enzyme inhibitor (ACEI) on systemic, pulmonary, and cerebral blood flow in post bidirectional cavopulmonary connection (BCPC) patients. [ Time Frame: This outcome will be measured following the cardiac catheterization procedure (~20 mins after drug is administered) ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: August 2008
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Enalaprilat
Enalaprilat will be administered intravenously i.v. 0.01 mg/kg i.v. over 1 minute

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

Ages Eligible for Study:   2 Months to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00741156

Locations
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada
Contact: Kyong-Jin Lee, MD    (416)813-7326    kyong-jin.lee@sickkids.ca   
Principal Investigator: Kyong-Jin Lee, MD         
Sub-Investigator: Helen Holtby, MD         
Sub-Investigator: Lee Benson, MD         
Sub-Investigator: Rajiv Chaturvedi, MD         
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Kyong-Jin Lee, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Kyong-Jin Lee/Principal Investigator, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00741156     History of Changes
Other Study ID Numbers: 1000012255
Study First Received: August 25, 2008
Last Updated: August 25, 2008
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
pediatric
hypertension
congestive cardiomyopathy
angiotensin-converting enzyme inhibitor
cardiac catheterization

Additional relevant MeSH terms:
Cardiomyopathy, Dilated
Hypertension
Cardiomyopathies
Cardiomegaly
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angiotensin-Converting Enzyme Inhibitors
Enalaprilat
Enalapril
Enzyme Inhibitors
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014