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

Primary Purpose

Hypotension

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
nitroprusside
Sponsored by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypotension focused on measuring children, sodium nitroprusside, controlled hypotension, dose-response, pharmacokinetics, pharmacodynamics, safety, efficacy

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

1

2

3

4

Arm Description

Nitroprusside infusion 0.3 mcg/kg/min

nitroprusside infusion 1 mcg/kg/min

nitroprusside infusion 2 mcg/kg/min

nitroprusside 3 mcg/kg/min

Outcomes

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

Full Information

First Posted
August 25, 2005
Last Updated
May 26, 2009
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
Stanford University, Duke University
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1. Study Identification

Unique Protocol Identification Number
NCT00135668
Brief Title
Dose-Response Study of Sodium Nitroprusside in Children Requiring Controlled Hypotension in the Operating Room
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
Stanford University, Duke University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypotension
Keywords
children, sodium nitroprusside, controlled hypotension, dose-response, pharmacokinetics, pharmacodynamics, safety, efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
203 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Nitroprusside infusion 0.3 mcg/kg/min
Arm Title
2
Arm Type
Active Comparator
Arm Description
nitroprusside infusion 1 mcg/kg/min
Arm Title
3
Arm Type
Active Comparator
Arm Description
nitroprusside infusion 2 mcg/kg/min
Arm Title
4
Arm Type
Active Comparator
Arm Description
nitroprusside 3 mcg/kg/min
Intervention Type
Drug
Intervention Name(s)
nitroprusside
Intervention Description
nitroprusside IV infusion 0.3-3 mcg/kg/ min
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Secondary efficacy endpoints are:Offset MAP and time to return to offset MAP after the cessation of study medication;
Title
The change from baseline MAP during the initial 20 and 25 minutes of sodium nitroprusside infusion during the blinded infusion;
Title
The infusion rate of sodium nitroprusside that reduces MAP to a predetermined clinically meaningful target value +/- 10%;
Title
The proportion of patients who reach target MAP;
Title
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.
Title
Analyses will be stratified by age

10. Eligibility

Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Hammer, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Scott Schulman, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5401
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26217225
Citation
Drover DR, Hammer GB, Barrett JS, Cohane CA, Reece T, Zajicek A, Schulman SR. Evaluation of sodium nitroprusside for controlled hypotension in children during surgery. Front Pharmacol. 2015 Jul 6;6:136. doi: 10.3389/fphar.2015.00136. eCollection 2015.
Results Reference
derived
PubMed Identifier
23631460
Citation
Hammer GB, Connolly SG, Schulman SR, Lewandowski A, Cohane C, Reece TL, Anand R, Mitchell J, Drover DR. Sodium nitroprusside is not associated with metabolic acidosis during intraoperative infusion in children. BMC Anesthesiol. 2013 Apr 30;13:9. doi: 10.1186/1471-2253-13-9.
Results Reference
derived

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

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