Sedation With Dexmedetomidine During Cardiac Catheterization

The Pharmacodynamics, Safety, and Pharmacokinetics of Sedation With Dexmedetomidine in Children Undergoing Hemodynamic Cardiac Catheterization With Special Reference to the Pulmonary Vascular Bed

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Dexmedetomidine

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Refusal of Informed Consent/Assent
2. Subjects with single ventricle physiology
3. Pregnant or lactating females
4. Subjects with syndromes e.g. Trisomy 21 will be excluded due to variability in pharmacodynamic responses and airway instability during sedation
5. Inappropriate clinical or developmental status to undergo cardiac catheterization under conditions of spontaneous ventilation with a natural airway
6. Second or third degree heart block
7. Moderate - severe right ventricular dysfunction/failure
8. 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
9. Concomitant Medications - Investigational Drugs: Subjects who have received another investigational drug protocol 30 days prior to enrollment in this study
10. Subjects who in the opinion of the investigator may be non compliant with study schedules or procedures.
11. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Dexmedetomidine; This is a single center, dose escalation study of Dexmedetomidine in 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.; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Endpoint Will be the Change in PVR in Wood Units	Pulmonary vascular resistance (PVR) in Wood units calculated during cardiac catheterization;	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Sedation With DEX	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	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
Quantify the Effect of DEX on PVR in Pediatric Subjects With Pulmonary Hypertension (PHTN) and Its Dependence on Baseline PVR	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	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
Obtain Pharmacokinetic Data in This Population	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	6 hours
Demonstrate That DEX is a Safe Sedative in Pediatric Subjects With PHTN	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.	24 hours

Collaborators and Investigators

• Sponsor: Aruna Nathan
• Collaborators: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Aruna T Nathan, MBBS, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: February 15, 2010
• First Submitted That Met QC Criteria: February 19, 2010
• First Posted (Estimate): February 22, 2010

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 4, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Pediatric; Pulmonary Hypertension; Sedation; Cardiac Catheterization; Pulmonary Vascular Resistance
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 09-007076