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

The EMMES Corporation

Status and phase

Completed

Phase 2

Conditions

Hypotension

Treatments

Drug: Nitroprusside

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00135668

NICHD-2003-09-DR

N01HD43386-7-0-1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

211 patients

Sex

All

Ages

Under 17 years old

Volunteers

No 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

211 participants in 4 patient groups

0.3 mcg/kg/min

Active Comparator group

Description:

Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons.

Treatment:

Drug: Nitroprusside

1 mcg/kg/min

Active Comparator group

Description:

Treatment:

Drug: Nitroprusside

2 mcg/kg/min

Active Comparator group

Description:

Treatment:

Drug: Nitroprusside