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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hypotension

Intervention / Treatment
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* Drug: nitroprusside


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Nitroprusside infusion 0.3 mcg/kg/min | Drug: nitroprusside<br>* nitroprusside IV infusion 0.3-3 mcg/kg/ min<br>|
| Active Comparator: 2<br>nitroprusside infusion 1 mcg/kg/min | Drug: nitroprusside<br>* nitroprusside IV infusion 0.3-3 mcg/kg/ min<br>|
| Active Comparator: 3<br>nitroprusside infusion 2 mcg/kg/min | Drug: nitroprusside<br>* nitroprusside IV infusion 0.3-3 mcg/kg/ min<br>|
| Active Comparator: 4<br>nitroprusside 3 mcg/kg/min | Drug: nitroprusside<br>* nitroprusside IV infusion 0.3-3 mcg/kg/ min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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children, sodium nitroprusside, controlled hypotension, dose-response, pharmacokinetics, pharmacodynamics, safety, efficacy