Hypoxic-Ischemic EncephalopathyPRIMENCT01747863
Prospective Research in Infants With Mild Encephalopathy
An observational study of Hypoxic-Ischemic Encephalopathy and Brain Injury, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 7 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages Up to 6 hours
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy, Brain Injury, Neonatal Seizure
- What is being tested?
- Neurologic examination
- How many people
- 63 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Dec 2012to Jun 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 hours
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United States4 sites
The Ohio Stage University - Nationwide Children's Hospital
Columbus, Ohio, 43205-2664
University of Texas Southwestern
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
Brown University
Providence, Rhode Island, 02905
About this study
Official title: Prospective Research in Infants With Mild Encephalopathy: the PRIME Study.
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.
Read the 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.
- Being tested
- Neurologic examination
- Keywords
- Hypoxic Ischemic encephalopathy
- Medical subject headings
- Hypoxia-Ischemia, Brain, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurologic examinationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Mild NE | Infants with evidence of a perinatal event and NE who do not qualify for therapeutic hypothermia. Receives: Other: Neurologic examination |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 month
Secondary outcomes (4)
Percentage of Infants With Seizures
Development of clinical or electrographic seizures
Measured: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Length of Hospital Stay
Measured: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Percentage of Infants Who Need Gavage Feeds or Gastrostomy at Discharge Home
Measured: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Mortality Rate
Death during the hospitalization
Measured: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionDec 2015
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Brown University, University of Texas Southwestern Medical Center, Wayne State University, Mahidol University, Ohio State University, Imperial College London
- Responsible party
- Principal investigator, Guilherme Sant'Anna, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Guilherme Sant'Anna, MD, Principal investigator, McGill UniversityLina Chalak, MD, Principal investigator, University of TexasAbbot Laptook, MD, Principal investigator, Brown UniversitySeetha Shankaran, MD, Principal investigator, Wayne State UniversityChatchay Prempunpong, MD, Principal investigator, Mahidol UniversitySudhin Thayyil, MD, Principal investigator, Imperial College LondonPablo Sanchez, MD, Principal investigator, Ohio State UniversityPablo Sanchez, MD, Study director, The Ohio Stage University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01747863
- Sponsor's protocol ID
- PRIME01
- Other IDs
- 12-108-PED
- Acronym
- PRIME
- Status last verified
- Dec 2024
- First submitted
- 7 Dec 2012
- Last updated
- 28 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31301853Prempunpong 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.
PubMed 29095433
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Research in Infants With Mild Encephalopathy: the PRIME Study.
- ClinicalTrials.gov ID
- NCT01747863
- Acronym / sponsor ID
- PRIME / PRIME01
- Keywords
- Hypoxic Ischemic encephalopathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Collaborators
- Brown University, University of Texas Southwestern Medical Center, Wayne State University, Mahidol University, Ohio State University, Imperial College London
- Study start
- Dec 2012
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 12 Dec 2012 (estimated)
- Results
- Posted 28 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mild NE | – | Other: Neurologic examinationInfants with evidence of a perinatal event and NE who do not qualify for therapeutic hypothermia. |
Who may qualify
- Ages
- Up to 6 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neurologic examinationNeurologic 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. | Other | Mild NE |
Primary outcome
Percentage of Infants With Evidence of Neurological Dysfunction, Brain Injury and/or Abnormality.
Time frame: 1 month
Evidence of neurological dysfunction/injury/abnormality will be defined by any of these 3 criteria, as follows: 1. MRI = Brain MRI score of pattern of injury (NICHD-NRN) > 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.
4 secondary outcomes
Percentage of Infants With Seizures
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Length of Hospital Stay
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
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
Mortality Rate
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31301853Chalak 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.
- Derived from this study: PubMed 29095433Prempunpong 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guilherme Sant'Anna, MD principal investigator
McGill University
Lina Chalak, MD principal investigator
University of Texas
Abbot Laptook, MD principal investigator
Brown University
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypoxic-Ischemic Encephalopathy and Brain Injury, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada, Thailand, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Infants With Evidence of Neurological Dysfunction, Brain Injury and/or Abnormality. (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01747863, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2025.