Sedation With Dexmedetomidine During Cardiac Catheterization

This study has been completed.
Sponsor:
Collaborator:
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
Aruna Nathan, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01072643
First received: February 15, 2010
Last updated: October 1, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Hypertension
Drug: Dexmedetomidine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Pharmacodynamics, Safety, and Pharmacokinetics of Sedation With Dexmedetomidine in Children Undergoing Hemodynamic Cardiac Catheterization With Special Reference to the Pulmonary Vascular Bed

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • The Primary endpoint will be the change in PVR in Wood units [ Time Frame: 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy of sedation with DEX [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • To quantify the effect of DEX on PVR in pediatric subjects with pulmonary hypertension and its dependence on baseline PVR [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • To obtain pharmacokinetic data in this population [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
  • To demonstrate that DEX is a safe sedative in pediatric subjects with PHTN [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

Enrollment: 4
Study Start Date: March 2010
Study Completion Date: April 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Precedex

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. 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.

  Eligibility

Ages Eligible for Study:   8 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01072643

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Aruna Nathan
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Aruna T Nathan, MBBS Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Aruna Nathan, Attending Physician, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01072643     History of Changes
Other Study ID Numbers: 09-007076
Study First Received: February 15, 2010
Last Updated: October 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital of Philadelphia:
Sedation
Pulmonary Hypertension
Pediatric
Cardiac Catheterization
Pulmonary Vascular Resistance

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014