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

NCT00135668 | Completed Phase 2 Results DMC

• 2 other identifiers: NICHD-2003-09-DRN01HD43386-7-0-1
• Study Type: interventional
• Target: 211
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypotension

Keywords

children; sodium nitroprusside; controlled hypotension; dose-response; pharmacokinetics; pharmacodynamics; safety; efficacy

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Change From Baseline MAP Nitroprusside Infusion During the Blinded Infusion;

  25 minutes

• Infusion Rate of Sodium Nitroprusside That Reduces MAP to a Predetermined Clinically Meaningful Target Value +/- 10%;

  Up to the end of open label treatment (Approximately 120 minutes)

• Number of Participants Who Reach Target MAP;

  To the end of open label treatment (approximately 120 minutes)

Study Arms (4)

0.3 mcg/kg/min

ACTIVE COMPARATOR

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.

Drug: Nitroprusside

1 mcg/kg/min

ACTIVE COMPARATOR

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.

Drug: Nitroprusside

2 mcg/kg/min

ACTIVE COMPARATOR

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

Drug: Nitroprusside

3 mcg/kg/min

ACTIVE COMPARATOR

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

Drug: Nitroprusside

Interventions

Nitroprusside DRUG

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).

Also known as: Sodium Nitroprusside IV infusion 0.3 mcg/kg/ min

0.3 mcg/kg/min

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Emmes Company, LLC: lead
• Stanford University: collaborator
• Duke University: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305-5401, United States

Location

Related Publications (2)

• 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.

  PMID: 26217225 DERIVED

• 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.

  PMID: 23631460 DERIVED

MeSH Terms

Conditions

Hypotension

Interventions

Nitroprusside

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Results Point of Contact

• Title: Scott Schulman, MD
• Organization: Duke University Medical Center

schul003@mc.duke.edu

919-681-4877

Study Officials

• Gregory Hammer, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Scott Schulman, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2005
• First Posted: August 26, 2005
• Study Start: August 1, 2005
• Primary Completion: March 1, 2008
• Study Completion: February 1, 2009
• Last Updated: January 2, 2024
• Results First Posted: January 2, 2024

Record last verified: 2023-12

Locations

US (1)