Dose-Response Study of Sodium Nitroprusside in Children Requiring Controlled Hypotension in the Operating Room

This study has been completed.
Sponsor:
Collaborators:
Stanford University
Duke University
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00135668
First received: August 25, 2005
Last updated: May 26, 2009
Last verified: May 2009
  Purpose

Sodium nitroprusside (SNP) has been approved for control of blood pressure in adults, yet there are no controlled studies in children. The purpose of this study is to determine the efficacy and safety of sodium nitroprusside in children who will be having surgery, and who require blood pressure lowering in order to decrease the amount of blood loss during their surgery.


Condition Intervention Phase
Hypotension
Drug: nitroprusside
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Multicenter, Randomized, Double-Blind, Parallel Group, Dose-Ranging, Effect-Controlled Study to Determine the Pharmacokinetics and Pharmacodynamics of Sodium Nitroprusside in Pediatric Subjects

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • The primary efficacy endpoint is the change in mean arterial pressure (MAP) from the baseline MAP after 30 minutes of blinded study drug administration with sodium nitroprusside

Secondary Outcome Measures:
  • Secondary efficacy endpoints are:Offset MAP and time to return to offset MAP after the cessation of study medication;
  • The change from baseline MAP during the initial 20 and 25 minutes of sodium nitroprusside infusion during the blinded infusion;
  • The infusion rate of sodium nitroprusside that reduces MAP to a predetermined clinically meaningful target value +/- 10%;
  • The proportion of patients who reach target MAP;
  • The change in vital signs (i.e., systolic blood pressure [SBP], diastolic blood pressure [DBP], and heart rate [HR]) from baseline to 10, 15, 20, and 30 minutes post-infusion initiation.
  • Analyses will be stratified by age

Enrollment: 203
Study Start Date: August 2005
Study Completion Date: February 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Nitroprusside infusion 0.3 mcg/kg/min
Drug: nitroprusside
nitroprusside IV infusion 0.3-3 mcg/kg/ min
Active Comparator: 2
nitroprusside infusion 1 mcg/kg/min
Drug: nitroprusside
nitroprusside IV infusion 0.3-3 mcg/kg/ min
Active Comparator: 3
nitroprusside infusion 2 mcg/kg/min
Drug: nitroprusside
nitroprusside IV infusion 0.3-3 mcg/kg/ min
Active Comparator: 4
nitroprusside 3 mcg/kg/min
Drug: nitroprusside
nitroprusside IV infusion 0.3-3 mcg/kg/ min

Detailed Description:

The trial is a multicenter randomized, double-blind, parallel group, dose-ranging, effect-controlled study examining the effects of sodium nitroprusside in pediatric subjects requiring relative hypotension during a surgical or medical procedure. The goal is to establish the starting and maximum infusion rates that afford optimum blood pressure control in children and a safe dosing regimen in children. The objective is to describe the relationship between the infusion rate of nitroprusside and changes in blood pressure.

The specific aims of this trial are:

  1. To define the onset and offset of blood pressure lowering effects of nitroprusside to obtain adequate instructions for dose titration in the pediatric population.
  2. To construct a dose-response model that defines the relationship between nitroprusside infusion rate and changes in blood pressure in pediatric subjects.
  3. To assess the safety of nitroprusside administration in pediatric subjects requiring controlled reduction of blood pressure.
  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Study subjects must meet all of the following criteria:

  • Subject is less than 17 years of age
  • Neonates must be full-term gestation and have a body weight of at least 2.5 kg
  • Subject requires pharmacologically-induced hypotension for acute blood pressure management for surgery or other invasive procedure, e.g., cerebral artery embolization
  • Duration of the subject's controlled hypotension is expected to be ≥ 2 hours
  • Subject requires general anesthesia with endotracheal intubation
  • Subject requires placement of intra-arterial line during the surgical or medical procedure
  • The subject's parent or legal guardian gives permission (informed consent) and subject gives assent when appropriate.

Exclusion Criteria:

Subjects will be excluded if any of the following criteria exist:

  • Subject has a known allergy to SNP
  • Subject has a known mitochondrial cytopathy with a disorder of oxidative phosphorylation or of respiratory chain enzymes
  • Subject has a contraindication to vasodilator therapy for control of blood pressure during surgery or procedures
  • Subject has participated in other clinical trials for investigational drugs and/or devices within 30 days prior to enrollment
  • Subject has any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures
  • Subject is moribund (death likely to occur within 48 hours)
  • Subject has a positive result for the urine or serum human chorionic gonadotropin (HCG) test administered at screening.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00135668

Locations
United States, California
Stanford University
Stanford, California, United States, 94305-5401
Sponsors and Collaborators
Stanford University
Duke University
Investigators
Principal Investigator: Gregory Hammer, MD Stanford University
Principal Investigator: Scott Schulman, MD Duke University
  More Information

No publications provided

Responsible Party: Greg Hammer MD, Stanford University
ClinicalTrials.gov Identifier: NCT00135668     History of Changes
Other Study ID Numbers: NICHD-2003-09-DR, NO1-HD-4-3386
Study First Received: August 25, 2005
Last Updated: May 26, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
children
sodium nitroprusside
controlled hypotension
dose-response
pharmacokinetics
pharmacodynamics
safety
efficacy

Additional relevant MeSH terms:
Hypotension
Vascular Diseases
Cardiovascular Diseases
Nitroprusside
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on April 17, 2014