Prospective Research in Infants With Mild Encephalopathy

Brain Injury Clinical Trial

— PRIME  

Official title:

Prospective Research in Infants With Mild Encephalopathy: the PRIME Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01747863
• Other study ID #: PRIME01
• Secondary ID: 12-108-PED
• Status: Completed
• Phase: N/A
• First received: December 7, 2012
• Last updated: September 21, 2017
• Start date: December 2012
• Est. completion date: June 2017

Study information

• Verified date: September 2017
• Source: McGill University Health Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A multicenter observational pilot study will be conducted to determine the natural history of infants with early diagnosis (≤ 6 hrs of age) of mild neonatal encephalopathy (NE) who are not qualified for therapeutic hypothermia. The intervention includes: neurologic examination by using modified Sarnat score at ≤ 6 hrs of age, 24 hrs and before discharge home, amplitude-integrated electroencephalography (aEEG) at 6 ± 3 hrs of age, brain MRI at before discharge home to 30 days of age and follow-up at 18-22 months of age. Primary outcome is the percentage of mild NE infants with evidence of brain injury defined by the presence of at least 1 abnormality of brain MRI, aEEG or neurologic examination in the neonatal period. Secondary outcome is the percentage of brain MRI, aEEG and neurological exam abnormalities, seizure, length of hospital stay, need of gavage feeds or gastrostomy at discharge home, death and long-term outcome.

Description:

Globally, an estimated 1.8 to 7.7 infants per 1000 live term births suffer from perinatal asphyxia, which remains an important cause of neonatal encephalopathy (NE) and neurodevelopmental impairment. Over the last six years, several randomized control trials have demonstrated that prolonged and moderate therapeutic hypothermia (TH) reduces the rate of death or disability at 18 months of age among infants who survived. In these trials, infants were eligible if there was evidence of perinatal hypoxia-ischemia and a moderate or severe degree of encephalopathy on neurological evaluation performed at ≤ 6 hrs of age. However, it has been recognized that the level of NE may change over time. Preliminary and unpublished observations from our group indicated that some infants who were not classified as moderate or severe NE had neurological abnormalities at discharge or evidence of brain injury on MRI performed during the neonatal period. Unfortunately, precise data on the outcomes of this specific population is not clear. Since TH is not offered to this population, the outcomes of infants that do not qualify for TH based on neurological evaluation performed ≤ 6 hrs of life requires a more precise investigation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 2017
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Hours

Eligibility

Inclusion Criteria:

• Infants with birth weight > or = 1800g and gestational age > or = 36 weeks AND

• Admission to neonatal intensive care unit (NICU) for possible hypothermia at < or = 6hr of life

Exclusion Criteria:

• Infants with normal neurological evaluation

• Major congenital abnormalities

• Refusal of informed consent

• Infants who receive passive or active cooling prior to the NICU admission

• Infants that develop seizures or moderate/severe NE within the first 24 hr of life and are initiated on therapeutic hypothermia after 6 hr of life.

Related Conditions & MeSH terms

• Brain Diseases
• Brain Injuries
• Brain Injury
• Brain Ischemia
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy
• Neonatal Seizure
• Seizures

Intervention

Other:
• Neurologic examination
Neurologic examination includes: (1) neurologic examination using modify Sarnat score at </= 6 hrs of age, 24 hrs and at discharge home, (2) aEEG at 6 ± 3 hrs of age, (3) Brain MRI before discharge home to 30 days of age.

Locations

Country	Name	City	State
Canada	Montreal Children's Hospital	Montreal	Quebec
Thailand	Mahidol University - Ramathibodi Hospital	Bangkok
United Kingdom	Imperial College London	London
United States	The Ohio Stage University - Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Brown University	Providence	Rhode Island

Sponsors (7)

Lead Sponsor	Collaborator
McGill University Health Center	Brown University, Imperial College London, Mahidol University, Ohio State University, University of Texas Southwestern Medical Center, Wayne State University

Countries where clinical trial is conducted

United States,  Canada,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Long-term neurodevelopment	Long-term outcomes (18-22 months of age): Severe disability if there is a Bayley III Cognitive score < 70, severe cerebral palsy (CP), defined by the Gross Motor Function Classification System (GMFCS) grade level 3 to 5, blindness or profound hearing loss. Moderate disability will be defined as the Bayley Cognitive score is 70-84 and either seizures, moderate CP (defined by GMFCS grade level 2) or a hearing deficit requiring amplification to understand commands. Mild disability will be defined by a cognitive score 70-84, or a cognitive score = 85 and either presence of mild or moderate CP (GMFCS grade levels 1 or 2), a seizure disorder or hearing loss with or without amplification. Normal will be defined as Bayley III Cognitive score = 85 without any visual or hearing impairment, or CP.	18-22 months of age
Primary	Percentage of infants with evidence of neurological dysfunction, brain injury and/or abnormality.	Evidence of neurological dysfunction/injury/abnormality will be defined by any of these 3 criteria, as follows: MRI = Brain MRI score of pattern of injury (NICHD-NRN) > 0,; aEEG = abnormal background pattern on aEEG (voltage or background pattern) at 6 ± 3 hrs of age.; Any abnormality on the neurological at discharge exam.	1 month
Secondary	Percentage of infants with seizures	Development of clinical or electrographic seizures	Participants will be followed for the duration of hospital stay, an expected average of 3 days
Secondary	Length of hospital stay		Participants will be followed for the duration of hospital stay, an expected average of 3 days
Secondary	Percentage of infants who need gavage feeds or gastrostomy at discharge home		Participants will be followed for the duration of hospital stay, an expected average of 3 days
Secondary	Mortality rate	Death during the hospitalization	Participants will be followed for the duration of hospital stay, an expected average of 3 days