The Acute Effects of the Angiotensin-converting Enzyme Inhibitor Enalaprilat on Flow Distribution
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|ClinicalTrials.gov Identifier: NCT00741156|
Recruitment Status : Completed
First Posted : August 26, 2008
Results First Posted : December 18, 2015
Last Update Posted : December 18, 2015
|Condition or disease||Intervention/treatment||Phase|
|Hypertension Congestive Cardiomyopathy||Drug: Enalaprilat||Phase 3|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
enalaprilat 0.005-0.01 mg/kg intravenous x 1 dose
Enalaprilat will be administered intravenously i.v. 0.005 - 0.01 mg/kg i.v. over 1 minute
Other Name: Vasotec
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT00741156
|The Hospital for Sick Children|
|Toronto, Ontario, Canada|
|Principal Investigator:||Kyong-Jin Lee, MD||The Hospital for Sick Children|