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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.
 
ClinicalTrials.gov Identifier: NCT00741156
Recruitment Status : Completed
First Posted : August 26, 2008
Results First Posted : December 18, 2015
Last Update Posted : December 18, 2015
Sponsor:
Information provided by (Responsible Party):
Kyong-Jin Lee, The Hospital for Sick Children

Tracking Information
First Submitted Date  ICMJE August 25, 2008
First Posted Date  ICMJE August 26, 2008
Results First Submitted Date  ICMJE July 26, 2013
Results First Posted Date  ICMJE December 18, 2015
Last Update Posted Date December 18, 2015
Study Start Date  ICMJE July 2008
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2015)
  • Systemic, Pulmonary and Cerebral Blood Flow at Baseline and After Enalaprilat [ Time Frame: Baseline and after enalaprilat ]
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2008)
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) ]
Change History Complete list of historical versions of study NCT00741156 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Acute Effects of the Angiotensin-converting Enzyme Inhibitor Enalaprilat on Flow Distribution
Official Title  ICMJE The Acute Effects of the Angiotensin-converting Enzyme Inhibitor Enalaprilat on Flow Distribution After the Bidirectional Cavopulmonary Connection
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypertension
  • Congestive Cardiomyopathy
Intervention  ICMJE Drug: Enalaprilat
Enalaprilat will be administered intravenously i.v. 0.005 - 0.01 mg/kg i.v. over 1 minute
Other Name: Vasotec
Study Arms  ICMJE Experimental: Enalaprilat
enalaprilat 0.005-0.01 mg/kg intravenous x 1 dose
Intervention: Drug: Enalaprilat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 16, 2015)
12
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2008)
15
Actual Study Completion Date  ICMJE January 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Months to 5 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00741156
Other Study ID Numbers  ICMJE 1000012255
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kyong-Jin Lee, The Hospital for Sick Children
Study Sponsor  ICMJE The Hospital for Sick Children
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kyong-Jin Lee, MD The Hospital for Sick Children
PRS Account The Hospital for Sick Children
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP