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

Selective Head Cooling With Mild Systemic Hypothermia After Neonatal Hypoxic-Ischemic Encephalopathy: A Multi-Center Randomized Controlled Trial in China

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

Study Overview

• Status: Completed
• Conditions: Hypoxic-Ischemic Encephalopathy
• Intervention / Treatment: Device: Cooling cap (YJW608-04B)

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 Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Children's Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Normothermia; Rectal temperature was maintained at 36.0-37.5 degree C.
Experimental: Hypothermia; 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.	Device: Cooling cap (YJW608-04B); A semiconductor water circulation cooling device (YJW608-04B, Henyang Radio Manufactory, Hunan, China) was used to conduct head cooling. The hypothermia 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.; Other Names: YJW608-04B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	The number of deaths by 18 months of age.	18 months
Severe Neurodevelopmental Disability	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).	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Events	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.	18 months

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Qingdao Children's Hospital; Guangxi Maternity and Infant health Hospital; Quanzhou Children's Hospital; The Second Hospital of Nanjing Medical University
• Investigators: Study Chair: Xiaomei Shao, M.D, Children's Hospital, Fudan University

Publications and helpful links

General Publications

• Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005 Feb 19-25;365(9460):663-70. doi: 10.1016/S0140-6736(05)17946-X.

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): June 1, 2004
• Study Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: January 2, 2009
• First Submitted That Met QC Criteria: April 28, 2009
• First Posted (Estimate): April 29, 2009

Study Record Updates

• Last Update Posted (Estimate): May 28, 2009
• Last Update Submitted That Met QC Criteria: May 1, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: safety; efficacy; neonate; hypothermia; hypoxic-ischemic encephalopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Body Temperature Changes; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypothermia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: Engineering 211