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

Hypotension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00135668
• Other study ID #: NICHD-2003-09-DR
• Secondary ID: N01HD43386-7-0-1
• Status: Completed
• Phase: Phase 2
• Start date: August 2005
• Est. completion date: February 2009

Study information

• Verified date: December 2023
• Source: The Emmes Company, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: February 2009
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypotension

Intervention

Drug:
• Nitroprusside
Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS (Interactive Voice Response System).
• Nitroprusside
Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS.
• Nitroprusside
Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS.
• Nitroprusside
Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
The Emmes Company, LLC	Duke University, Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mean Arterial Pressure (MAP) From the Baseline MAP	From the Baseline MAP until the end of the blinded phase; scheduled for 30 min	Approximately 30 minutes
Primary	Overall Summary of Tolerability/Adverse Events (AEs) for ITT Safety Population	Treatment-emergent AEs (TEAEs) were defined as an AE experienced by the patient that was either first observed after the initiation of study drug (blinded or open-label) or represented an exacerbation (usually in severity) of a pre existing condition observed prior to treatment. Subjects will be followed for 30 days after discontinuation of study drug. The occurrence of Serious Adverse Events (SAEs) will be monitored for 30 days.	30 days
Secondary	Change From Baseline MAP Nitroprusside Infusion During the Blinded Infusion;	Change From Baseline in MAP (mmHg) After 20 and 25 Minutes Double-Blind Infusion (Overall) for ITT Efficacy Evaluable Population.	25 minutes
Secondary	Infusion Rate of Sodium Nitroprusside That Reduces MAP to a Predetermined Clinically Meaningful Target Value +/- 10%;	Infusion rate of sodium nitroprusside at which a predetermined clinically meaningful target value (+/- 10%) of MAP was achieved during study drug administration	Up to the end of open label treatment (Approximately 120 minutes)
Secondary	Number of Participants Who Reach Target MAP;	Blinded Study Drug Administration Period: Started with study drug administration following stabilization of anesthesia. Patients were administered a blinded dose of SNP for up to 30 mins.; This period ended at the start of open-label study drug infusion or at the completion of the blinded infusion if no open-label study drug was given. The follow-up period immediately followed for those patients not receiving open-label infusion.; Blinded Treatment Phase II - gap between the end of blinded study drug infusion and the start of open-label study drug infusion; Open-label treatment phase began with the start of open-label study drug infusion and was at least 90 mins in duration. SNP was initiated at a dose deemed appropriate by the investigator and was gradually adjusted to reach a target MAP based on clinical presentation and needs of the patient. Target MAP was not to be < 50 mmHg (40 mmHg for patients < 30 days of age). This period ended at the completion of open-label infusion.	To the end of open label treatment (approximately 120 minutes)