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
Controlled Hypotension	Drug: Sodium nitroprusside	Phase II

Further Study Details: 

Primary Outcomes: The primary efficacy endpoint is the change in MAP from the baseline MAP after 30 minutes of blinded study drug administration with sodium nitroprusside.
Secondary Outcomes: Secondary efficacy endpoints are:; 1. Offset MAP and time to return to offset MAP after the cessation of study medication.; 2. The change from baseline MAP during the initial 20 and 25 minutes of sodium nitroprusside infusion during the blinded infusion.; 3. The infusion rate of sodium nitroprusside that reduces MAP to a predetermined clinically meaningful target value +/- 10%.; 4. The proportion of patients who reach target MAP.; 5. The change in vital signs (i.e., SBP, DBP, and HR) from baseline to 10, 15, 20, and 30 minutes post-infusion initiation.; Analyses will be stratified by age.
Expected Total Enrollment:  200

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.

Ages Eligible for Study:  up to  17 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Study subjects must meet all of the following criteria:

  1. Subject is less than 17 years of age
  2. Neonates must be full-term gestation and have a body weight of at least 2.5 kg
  3. Subject requires pharmacologically-induced hypotension for acute blood pressure management for surgery or other invasive procedure, e.g., cerebral artery embolization
  4. Duration of the subject''''s controlled hypotension is expected to be ≥ 2 hours
  5. Subject requires general anesthesia with endotracheal intubation
  6. Subject requires placement of intra-arterial line during the surgical or medical procedure
  7. 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:

1. Subject has a known allergy to SNP
2. Subject has a known mitochondrial cytopathy with a disorder of oxidative phosphorylation or of respiratory chain enzymes
3. Subject has a contraindication to vasodilator therapy for control of blood pressure during surgery or procedures
4. Subject has participated in other clinical trials for investigational drugs and/or devices within 30 days prior to enrollment
5. Subject has any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures
6. Subject is moribund (death likely to occur within 48 hours)
7. Subject has a positive result for the urine or serum HCG test administered at screening.

Please refer to this study by ClinicalTrials.gov identifier  NCT00135668

Gregory Hammer, MD      650-723-7835    ham@stanford.edu
Nancy Federspiel, PhD      650-725-7512    nfeder@stanford.edu

California
      Stanford University, Stanford,  California,  94305-5401,  United States; Recruiting

Study chairs or principal investigators

Gregory Hammer, MD,  Principal Investigator,  Stanford University   

Study ID Numbers:  NICHD-2003-09-DR; NO1-HD-4-3386
Last Updated:  August 25, 2005
Record first received:  August 25, 2005
ClinicalTrials.gov Identifier:  NCT00135668
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-30