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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 211
- 试验地点
- 1
- 主要终点
- Overall Summary of Tolerability/Adverse Events (AEs) for ITT Safety Population
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
0.3 mcg/kg/min
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.
干预措施: Nitroprusside (Drug)
1 mcg/kg/min
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.
干预措施: Nitroprusside (Drug)
2 mcg/kg/min
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
干预措施: Nitroprusside (Drug)
3 mcg/kg/min
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
干预措施: Nitroprusside (Drug)
结局指标
主要结局
Overall Summary of Tolerability/Adverse Events (AEs) for ITT Safety Population
时间窗: 30 days
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.
Change in Mean Arterial Pressure (MAP) From the Baseline MAP
时间窗: Approximately 30 minutes
From the Baseline MAP until the end of the blinded phase; scheduled for 30 min
次要结局
- 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))