Hypoxic-Ischemic Encephalopathy
Conditions
Keywords
hypothermia, neonate, hypoxic-ischemic encephalopathy, efficacy, safety
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.
Interventions
DEVICECooling 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.
Sponsors
Qingdao Children's Hospital
Guangxi Maternity and Infant health Hospital
Quanzhou Children's Hospital
The Second Hospital of Nanjing Medical University
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Hours
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
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.
Participants by arm
| Arm | Count |
|---|---|
| Normothermia Rectal temperature in the group was maintained at 36 to 37.5 degree C. | 116 |
| 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. | 140 |
| Total | 256 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 20 | 21 |
Baseline characteristics
| Characteristic | Normothermia | Hypothermia | Total |
|---|---|---|---|
| Age, Customized <=6 hours | 4.03 hour STANDARD_DEVIATION 1.21 | 4.12 hour STANDARD_DEVIATION 1.59 | 4.07 hour STANDARD_DEVIATION 1.38 |
| Sex: Female, Male Female | 19 Participants | 25 Participants | 44 Participants |
| Sex: Female, Male Male | 97 Participants | 115 Participants | 212 Participants |
Outcome results
Primary
Death
The number of deaths by 18 months of age.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normothermia | Death | 27 participants |
| Hypothermia | Death | 22 participants |
Primary
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).
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normothermia | Severe Neurodevelopmental Disability | 19 participants |
| Hypothermia | Severe Neurodevelopmental Disability | 11 participants |
Secondary
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.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normothermia | Major Adverse Events | 3 participants |
| Hypothermia | Major Adverse Events | 4 participants |