Clinical trial NCT01747863: Prospective Research in Infants With Mild Encephalopathy
Official title: Prospective Research in Infants With Mild Encephalopathy: the PRIME Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypoxic-Ischemic Encephalopathy
Brain Injury
Neonatal Seizure
Keywords: Hypoxic Ischemic encephalopathy
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Brown University
name: University of Texas Southwestern Medical Center
name: Wayne State University
name: Mahidol University
name: Ohio State University
name: Imperial College London
First posted: 2012-12-12
Enrollment: 63
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Infants with evidence of a perinatal event and NE who do not qualify for therapeutic hypothermia. NE will be defined as the presence of abnormal neurological findings on the modified Sarnat Score performed at ≤ 6 hrs of life. Evidence of a perinatal event will include criteria described in details in the whole body hypothermia trial (NEJM, 2005). The level of NE will be defined by the neurological exam performed by certified neonatologists working at the 6 centers.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Infants With Evidence of Neurological Dysfunction, Brain Injury and/or Abnormality.
timeFrame: 1 month
Secondary outcomes:
measure: Percentage of Infants With Seizures
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
measure: Length of Hospital Stay
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
measure: Percentage of Infants Who Need Gavage Feeds or Gastrostomy at Discharge Home
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
measure: Mortality Rate
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Other outcomes:
measure: Long-term Neurodevelopment
timeFrame: 18-22 months of age
Locations:
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Columbus
country: United States
facility: The Ohio Stage University - Nationwide Children's Hospital
state: Ohio
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Bangkok
country: Thailand
facility: Mahidol University - Ramathibodi Hospital
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: McGill University
name: Guilherme Sant'Anna, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Lina Chalak, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brown University
name: Abbot Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mahidol University
name: Chatchay Prempunpong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Sudhin Thayyil, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Pablo Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Ohio Stage University
name: Pablo Sanchez, MD
role: STUDY_DIRECTOR
affiliation: McGill University
name: Guilherme Sant'Anna, MD
role: STUDY_CHAIR
References:
citation: Chalak LF, Adams-Huet B, Sant'Anna G. A Total Sarnat Score in Mild Hypoxic-ischemic Encephalopathy Can Detect Infants at Higher Risk of Disability. J Pediatr. 2019 Nov;214:217-221.e1. doi: 10.1016/j.jpeds.2019.06.026. Epub 2019 Jul 10.
citation: Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.