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

• Sponsor: Fudan University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00890409
• Collaborator: Qingdao Children's Hospital (Other), Guangxi Maternity and Infant health Hospital (Other), Quanzhou Children's Hospital (Other), The Second Hospital of Nanjing Medical University (Other)
• Enrollment: 256
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 6.6

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Hypoxic-Ischemic Encephalopathy	Device: Cooling cap (YJW608-04B)	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 256 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Selective Head Cooling With Mild Systemic Hypothermia After Neonatal Hypoxic-Ischemic Encephalopathy: A Multi-Center Randomized Controlled Trial in China
• Study Start Date: May 1, 2002
• Actual Primary Completion Date: Jun 1, 2004
• Actual Study Completion Date: Aug 1, 2005

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Death [18 months]

   The number of deaths by 18 months of age.

2. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 6 Hours
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital, Fudan University	Shanghai	Shanghai	China	201102

Sponsors and Collaborators

• Fudan University
• 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

Study Documents (Full-Text)

None provided.

More Information

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.

• ClinicalTrials.gov Identifier: NCT00890409
• Other Study ID Numbers: Engineering 211
• First Posted: Apr 29, 2009
• Last Update Posted: May 28, 2009
• Last Verified: May 1, 2009

• Keywords provided by , ,: hypothermia; neonate; hypoxic-ischemic encephalopathy; efficacy; safety
• Additional relevant MeSH terms: Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain; Ischemia; Hypothermia; Hypoxia

Study Results

Participant Flow

Recruitment Details	Dates of the recruitment period: May 2002 to August 2005; Types of location: Children's Hospital or Women and Children's Medical Centre.

Arm/Group Title	Normothermia	Hypothermia
Arm/Group Description	Rectal temperature in the group was maintained at 36 to 37.5 degree C.	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.
Period Title: Overall Study
STARTED	116	140
COMPLETED	96	119
NOT COMPLETED	20	21

Baseline Characteristics

Arm/Group Title	Normothermia	Hypothermia	Total
Arm/Group Description	Rectal temperature in the group was maintained at 36 to 37.5 degree C.	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.	Total of all reporting groups
Overall Participants	116	140	256
Age, Customized (hour) [Mean (Standard Deviation) ]
<=6 hours	4.03 (1.21)	4.12 (1.59)	4.07 (1.38)
Sex: Female, Male (Count of Participants)
Female	19 16.4%	25 17.9%	44 17.2%
Male	97 83.6%	115 82.1%	212 82.8%

Outcome Measures

1. Primary Outcome

Title	Death
Description	The number of deaths by 18 months of age.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normothermia	Hypothermia
Arm/Group Description	Rectal temperature in the group was maintained at 36 to 37.5 degree C.	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.
Measure Participants	96	119
Number [participants]	27 23.3%	22 15.7%

2. Primary Outcome

Title	Severe Neurodevelopmental Disability
Description	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).
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normothermia	Hypothermia
Arm/Group Description	Rectal temperature in the group was maintained at 36 to 37.5 degree C.	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.
Measure Participants	69	97
Number [participants]	19 16.4%	11 7.9%

3. Secondary Outcome

Title	Major Adverse Events
Description	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.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normothermia	Hypothermia
Arm/Group Description	Rectal temperature in the group was maintained at 36 to 37.5 degree C.	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.
Measure Participants	96	119
Number [participants]	3 2.6%	4 2.9%

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.