Prospective Research in Infants With Mild Encephalopathy (PRIME)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by McGill University Health Center
Sponsor:
Collaborators:
Brown University
University College London Hospitals
University of Texas Southwestern Medical Center
Wayne State University
Mahidol University
Information provided by (Responsible Party):
Guilherme Sant'Anna, McGill University Health Center
ClinicalTrials.gov Identifier:
NCT01747863
First received: December 7, 2012
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Hypoxic-Ischemic Encephalopathy
Brain Injury
Neonatal Seizure
Other: Neurologic examination

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Research in Infants With Mild Encephalopathy: the PRIME Study.

Resource links provided by NLM:


Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Percentage of infants with evidence of neurological dysfunction, brain injury and/or abnormality. [ Time Frame: 1 month ] [ Designated as safety issue: No ]

    Evidence of neurological dysfunction/injury/abnormality will be defined by any of these 3 criteria, as follows:

    1. MRI = NRN score of pattern of injury > 0,
    2. aEEG = abnormal background pattern on aEEG (voltage or background pattern) at 6 ± 3 hrs of age.
    3. Any abnormality on the neurological at discharge exam.


Secondary Outcome Measures:
  • Percentage of infants with seizures [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3 days ] [ Designated as safety issue: No ]
    Development of clinical or electrographic seizures

  • Length of hospital stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3 days ] [ Designated as safety issue: No ]
  • Percentage of infants who need gavage feeds or gastrostomy at discharge home [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3 days ] [ Designated as safety issue: No ]
  • Mortality rate [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3 days ] [ Designated as safety issue: No ]
    Death during the hospitalization


Other Outcome Measures:
  • Long-term neurodevelopment [ Time Frame: 18-22 months of age ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 57
Study Start Date: December 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Mild NE
Infants with evidence of a perinatal event and NE who do not qualify for therapeutic hypothermia.
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.

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

Ages Eligible for Study:   up to 6 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01747863

Contacts
Contact: Chatchay Prempunpong, MD 1 514 412 4400 ext 23063 chatchay.prempunpong@mail.mcgill.ca
Contact: Lina Chalak, MD 1-214-730-5437 Lina.Chalak@utsouthwestern.edu

Locations
United States, Michigan
Wayne State University Active, not recruiting
Detroit, Michigan, United States, 48201
United States, Rhode Island
Brown University Recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot Laptook, MD    401-274-1122 ext 1221    alaptook@wihri.org   
Contact: Birju A Shah, MD    1-401-274-1122    BShah@wihri.org   
Principal Investigator: Abbot Laptook, MD         
Sub-Investigator: Birju A Shah, MD         
United States, Texas
University of Texas Southwestern Active, not recruiting
Dallas, Texas, United States, 75235
Canada, Quebec
Montreal Children's Hospital Recruiting
Montreal, Quebec, Canada, H3H 1P3
Contact: Guilherme Sant' Anna, MD    1-514-412-4400 ext 23489    guilherme.santanna@mcgill.ca   
Contact: Chatchay Prempunpong, MD    1-514-412-4400 ext 23063    chatchaypr@gmail.com   
Principal Investigator: Chatchay Prempunpong, MD         
Principal Investigator: Guilherme Sant'Anna, MD         
Sub-Investigator: Pia Wintermark, MD         
Sub-Investigator: Rose Boyle, MN         
Sub-Investigator: Kim-anh Nguyen, MD         
Sub-Investigator: Jarred Garfinkle, MD         
Sub-Investigator: Louise Koclas, MD         
Thailand
Mahidol University Not yet recruiting
Bangkok, Thailand, 10400
Contact: Chatchay Prempunpong, MD    +66-2-201-1816 ext 15    chatchaypr@gmail.com   
Principal Investigator: Chatchay Prempunpong, MD         
United Kingdom
University College London Active, not recruiting
London, United Kingdom, WC1E 6AU
Sponsors and Collaborators
McGill University Health Center
Brown University
University College London Hospitals
University of Texas Southwestern Medical Center
Wayne State University
Mahidol University
Investigators
Principal Investigator: Guilherme Sant'Anna, MD McGill University
Principal Investigator: Lina Chalak, MD University of Texas
Principal Investigator: Abbot Laptook, MD Brown University
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Sudhin Thayyil, MD University College, London
Study Director: Pablo Sanchez, MD University of Texas
Study Chair: Guilherme Sant'Anna, MD McGill University Health Center
Principal Investigator: Chatchay Prempunpong, MD Mahidol University
  More Information

No publications provided

Responsible Party: Guilherme Sant'Anna, Associate Professor of Pediatrics, McGill University Health Center
ClinicalTrials.gov Identifier: NCT01747863     History of Changes
Other Study ID Numbers: PRIME01, 12-108-PED
Study First Received: December 7, 2012
Last Updated: June 21, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by McGill University Health Center:
Hypoxic Ischemic encephalopathy

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain

ClinicalTrials.gov processed this record on September 18, 2014