Safety and Efficacy of Hypothermia to Treat Neonatal Hypoxic-Ischemic Encephalopathy

Phase 3

Completed

• Conditions: Hypoxic-Ischemic Encephalopathy
• Interventions: Device: Cooling cap (YJW608-04B)

• Registration Number: NCT00890409
• Lead Sponsor: Fudan University

Brief Summary

The purpose of this study is to investigate the effectiveness and safety of selective head cooling (SHC) in neonatal hypoxic-ischemic encephalopathy (HIE).

Detailed Description

Hypoxic-ischemic encephalopathy (HIE) remains a major cause of neonatal death and long term disabilities. Data from animal studies have shown protective effects of mild hypothermia to both the mature and immature brain. Recently research priorities have moved from bench to bedside. Several studies have shown a trend for brain protection of mild to moderate hypothermia and mild hypothermia has emerged as a promising treatment for HIE. Therefore,the investigators organized a multi-centered randomized controlled trial of selective head cooling (SHC) combined with mild systemic hypothermia in HIE newborn infants.

Study Timeline

• Study Start: 2002-05
• Primary Completion: 2004-06
• Study Completion: 2005-08
• Study First Submitted: 2009-01-02
• Results First Submitted: 2009-01-02
• Study First Submitted QC: 2009-04-28
• Results First Submitted QC: 2009-04-28
• Study First Posted: 2009-04-29
• Results First Posted: 2009-04-29
• Status Verified: 2009-05
• Last Update Submitted: 2009-05-01
• Last Update Posted: 2009-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 256

Inclusion Criteria

• Age up to 6 hours
• Gestational age ≥ 36 weeks and birth weight ≥ 2500 g
• Apgar score ≤ 3 at 1 minute and ≤ 5 at 5 minutes, and/or cord blood gas pH < 7.0 or base deficit ≤ 16 mmol/L, and/or need for resuscitation or ventilation at 5 minutes of age
• Clinical signs of encephalopathy (seizures, coma, abnormal muscle tone and irregular breathing, etc)

Exclusion Criteria

• Major congenital abnormalities
• Infection
• Other etiology of induced brain injury
• Severe anemia (Hb < 120 g/L)

Eligible infants assessed for the severity of HIE according to criteria of the Neonatal Association of Chinese Academy of Pediatrics 25 modified from Sarnat and Sarnat 26 in 1986

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hypothermia	Cooling cap (YJW608-04B)	The group was fitted with a cooling cap around the head for 72 hours. The temperature of the cap could be adjusted between 5 to 20 degree C and was automatically regulated by a servo-controlled temperature probe placed in the nasopharynx to maintain the nasopharyngeal temperature at (34±0.2)degree C. All infants were nursed under a servo-controlled radiant warmer and the rectal temperature was maintained at 34.5 to 35 degree C. Head cooling was started within 6 hours after birth for 72 hours followed by spontaneous re-warming and the average time to reach the target temperature was 2 hours.

Primary Outcome Measures

Name	Time	Method
Death	18 months	The number of deaths by 18 months of age.
Severe Neurodevelopmental Disability	18 months	Severe disability was defined as cerebral palsy (CP) or mental retardation (MR). The definition of MR was development quotient (DQ) \<70 by Gesell's Child Development Scale and CP was based on the Criteria of a level 3 to 5 by the Gross Motor Function Classification System (GMFCS).

Secondary Outcome Measures

Name	Time	Method
Major Adverse Events	18 months	Major adverse events were defined as severe arrhythmia (II or III degree A-V block or atrial or ventricular arrhythmia), major venous thrombosis, refractory hypotension (mean blood pressure less than 40 mmHg), moderate or severe scleredema (greater or equal to 20% body surface area), and severe bleeding.

Trial Locations

Locations (1)

Children's Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China