Sedation With Dexmedetomidine During Cardiac Catheterization

Phase 2

Terminated

Conditions: Pulmonary Hypertension

Interventions: Drug: Dexmedetomidine

Registration Number: NCT01072643

Lead Sponsor: Aruna Nathan

Brief Summary: Clinical dose escalation drug trial to evaluate the effect of 3 different doses of dexmedetomidine on the pulmonary vascular bed in pediatric subjects with elevated pulmonary vascular resistance (PVR). The study will be conducted in 2 parts, with part 1 incorporating stopping rules to optimize safety of the drug in this population. The second part of this study will evaluate if the lowest safest dose, as determined in part 1, is adequate to provide effective sedation during a cardiac catheterization procedure.

Detailed Description: Clinical dose escalation drug trial to evaluate the effect of 3 different doses of dexmedetomidine on the pulmonary vascular bed in pediatric subjects with elevated pulmonary vascular resistance. The study will be conducted in 2 parts, with a pilot phase incorporating stopping rules to optimize safety of the drug in this population. Study subjects will include pediatric subjects with Pulmonary Hypertension (PHTN).

Part 1: This will be the dose escalation phase of the study. Twenty four evaluable subjects will be enrolled. Subjects will include pediatric subjects with pulmonary hypertension (PVR\>4WU) undergoing hemodynamic cardiac catheterization and vasoreactivity drug testing. Cohorts of 8 evaluable subjects will receive dose level 1, dose level 2, or dose level 3 of Dexmedetomidine (DEX). The dose will be escalated to the next dose of DEX once all subjects have been enrolled in the preceding DEX dose cohort, and safety has been established at that level. Inadequate sedation despite the highest dose of DEX at each level will be considered a treatment failure on an intention to treat basis. Part 2: This part of the study will be conducted after the pilot phase is safely completed, and the full complement of subjects will be recruited.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

Inclusion Criteria

Subjects with a diagnosis of pulmonary hypertension
Procedure - Planned cardiac catheterization procedure with spontaneous ventilation and natural airway
Patients who want sedation or general anesthetic for the procedure.
Age: Subjects ≥8 years and < 21 years
Adequate Renal Function defined As:Serum creatinine ≤ 1 mg/dL
Adequate Liver Function defined As:Total bilirubin ≤ 1.5 mg/dL alanine aminotransferase (ALT) ≤ 2 times the upper limit of normal
Informed Consent: All parents or legal guardians must sign a written informed consent.
Signed assent when developmentally appropriate
Negative pregnancy test in menstruating females and all females ≥ 12 yr

Exclusion Criteria

Refusal of Informed Consent/Assent
Subjects with single ventricle physiology
Pregnant or lactating females
Subjects with syndromes e.g. Trisomy 21 will be excluded due to variability in pharmacodynamic responses and airway instability during sedation
Inappropriate clinical or developmental status to undergo cardiac catheterization under conditions of spontaneous ventilation with a natural airway
Second or third degree heart block
Moderate - severe right ventricular dysfunction/failure
Subjects who, in the opinion of the investigator, are not appropriate candidates for an investigational drug study e.g. behavioral or anxiety disorders, inability to lie supine
Concomitant Medications - Investigational Drugs: Subjects who have received another investigational drug protocol 30 days prior to enrollment in this study
Subjects who in the opinion of the investigator may be non compliant with study schedules or procedures.
Non-English speaking subjects will be excluded due to need for direct communication from clinical and study staff during study procedures and the ability to complete study tools.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine	Dexmedetomidine	To study safety of DEX with regard to effect on PVR; There will be 3 study groups (n=8 per group). The groups will be based on DEX doses as follows- Group 1 - Bolus 1 mcg/kg followed by infusion 0.7 mcg/kg/hr Group 2 - Bolus 1.5 mcg/kg followed by infusion 1.05 mcg/kg/hr Group 3 - Bolus 2 mcg/kg followed by infusion 1.4 mcg/kg/hr

Primary Outcome Measures

Name	Time	Method
The Primary Endpoint Will be the Change in PVR in Wood Units	For each subject PVR will be measured by cardiac catheterization at T0 ( baseline measurement) , after DEX bolus (T1) which is given over 10 minutes and after 30 mins after start of the DEX infusion (T2) - Maximum upto 4 hours	Pulmonary vascular resistance (PVR) in Wood units calculated during cardiac catheterization;

Secondary Outcome Measures

Name	Time	Method
Efficacy of Sedation With DEX	Subjects will participate in a dose escalation study which will define minimal effective dose that results in effective sedation in ≥ 7 out of 8 patients in that dose cohort. Maximum upto 4 hours	The study was terminated early due to increased pulmonary vascular resistance (PVR) in one subject from To-T1 reaching the level of a predetermined stopping rule. Investigators suggested that it is premature to conclude that DEX does not adversely affect PVR
Quantify the Effect of DEX on PVR in Pediatric Subjects With Pulmonary Hypertension (PHTN) and Its Dependence on Baseline PVR	Every individual patient will be studied over maximum of 4 hours during the dose escalation phase. This part of the study will be completed in 1 year	The study was terminated early due to increased pulmonary vascular resistance (PVR) in one subject from To-T1 reaching the level of a predetermined stopping rule. Investigators suggested that it is premature to conclude that DEX does not adversely affect PVR
Obtain Pharmacokinetic Data in This Population	6 hours	The study was terminated early due to increased pulmonary vascular resistance (PVR) in one subject from To-T1 reaching the level of a predetermined stopping rule. Investigators suggested that it is premature to conclude that DEX does not adversely affect PVR
Demonstrate That DEX is a Safe Sedative in Pediatric Subjects With PHTN	24 hours	The study was terminated early due to increased pulmonary vascular resistance (PVR) in one subject from To-T1 reaching the level of a predetermined stopping rule. Investigators suggested that it is premature to conclude that DEX does not adversely affect PVR.