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Cool Prime Comparative Effectiveness Study for Mild HIE (COOLPRIME)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04621279
Recruitment Status : Not yet recruiting
First Posted : November 9, 2020
Last Update Posted : January 27, 2022
Sponsor:
Collaborators:
Nationwide Children's Hospital
University of California, San Francisco
Children's National Research Institute
Children's Hospital Los Angeles
Washington University School of Medicine
St. Louis University
University of Washington
Stanford University
Children's Hospital of Philadelphia
University of Utah Hospital
University of Pittsburgh Medical Center
Emory University
Children's Hospital Medical Center, Cincinnati
University College Cork
Information provided by (Responsible Party):
Lina Chalak, University of Texas Southwestern Medical Center

Brief Summary:
To determine effectiveness of therapy to improve neurodevelopmental outcomes in infants with mild HIE. To determine the adverse effects of TH in mild HIE on the neonate and his/her family. Determine heterogeneity of the treatment effect across key subgroups obtained in the first 6 hours after birth prior to the decision to initiate therapy.

Condition or disease Intervention/treatment
Mild Hypoxic Ischaemic Encephalopathy of Newborn Procedure: Normothermia Procedure: Whole body therapeutic hypothermia

Detailed Description:
This study leverages practice variation within and across 15 participating sites to compare the effectiveness of TH versus normothermia for mild HIE on neurodevelopmental outcomes at 2 years of age.After standardizing all aspects of clinical care for mild HIE (except for TH vs. normothermia)we will enroll 460 infants with mild HIE into the longitudinal, observational comparative effectiveness study.The central aim of the comparative longitudinal cohort of mild HIE is (1) to compare the effectiveness of hypothermia to normothermia on neurodevelopmental outcomes at 2 years, (2) determine the adverse effects of TH on the infant and his/her family; and (3) determine the heterogeneity of treatment effects (moderating effect) across mild HIE subgroups as determined by physiological biomarkers obtained during the 6 hours window to initiate hypothermia. The decision to apply TH or normothermia will be entirely determined by practice parameters at each site.

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Study Type : Observational
Estimated Enrollment : 460 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: COOLPRIME: Comparative Effectiveness for Cooling Prospectively Infants With Mild Encephalopathy
Estimated Study Start Date : December 1, 2022
Estimated Primary Completion Date : December 1, 2027
Estimated Study Completion Date : December 1, 2029

Group/Cohort Intervention/treatment
Mild Hypoxic Ischemic Encephaolpathy

Infant ≥ 360/7 weeks with evidence of BOTH 1) perinatal event fetal acidosis and 2) encephalopathy on exam.

  1. Perinatal depression as defined by NICHD based on at least one of the following; pH <7.00 in a cord gas or Base deficit ≥15 mmol/L in a gas (arterial or venous) obtained at <60 min of age, Apgar score <5 at 10 minutes, or Need for resuscitation at 10 minutes (i.e., chest compressions, or positive pressure respiratory support including endotracheal, mask ventilation, or CPAP).
  2. Mild encephalopathy, as defined by PRIME-study 1-6 hours after birth. At least 1 of 6 Sarnat criteria is scored as a mild, moderate, or severe abnormality, and Fewer than 3 of 6 Sarnat criteria are scored as a moderate or severe abnormality
Procedure: Normothermia
Usual care for first 72 hours for neonates with mild encephaolpathy maintaining core temperature 36.0 - 37.0.

Procedure: Whole body therapeutic hypothermia
Whole body therapeutic hypothermia (33.5°C + 0.5°C) for 72 hours begun by 6 hours of age, followed by rewarming at 0.5°C/hour for neonates with mild encephaolpathy per site standard of care practice.




Primary Outcome Measures :
  1. Composite Bayley IV [ Time Frame: 22-26 months of age. ]
    To compare the effectiveness of therapeutic hypothermia versus normothermia in each of the developmental domains (cognitive, language, motor) as a three dimensional vector.


Secondary Outcome Measures :
  1. MRI biomarkers [ Time Frame: 4-5 days of age. ]
    To determine the comparative effectiveness of TH based on the MRI injury score and the MRS measures of n-acetylaspartate and lactate.


Other Outcome Measures:
  1. Determine TH effect on prolonged length of stay. [ Time Frame: At time of discharge from hospital, up to 30 days from admission ]
    Determine TH effect on prolonged length of stay as defined as >7 day.

  2. Determine TH effect on adverse events. [ Time Frame: At time of discharge from hospital, up to 30 days from admission ]
    Determine adverse events from therapeutic hypothermia to include prolonged hospital stay shivering and possible exposure to narcotic/sedative agents bradycardia/cardiac arrhythmia, major vessel thrombosis or bleeding, thrombocytopenia and alteration of skin integrity.

  3. Parental measures of bonding. [ Time Frame: 4 months of age ]
    Parent-infant Status will be assessed using a validated consisting of Mother-to-Infant Bonding Scale score <2.

  4. Parent measure of stress. [ Time Frame: 4 months of age. ]
    Baby Care Questionnaire eliciting parental perspectives on feeding, sleeping, and soothing infants in the home environment and is indicative of a parent's reliance on structure and attunement to child cues and test-retest coefficients >0.81 associated with developmental outcomes.

  5. Heterogeneity of the Total Sarnat Sore. [ Time Frame: Day of life 1 ]
    Determine the heterogeneity of the treatment effect across subgroups assessing TH responses as a function of Total Sarnat Score (≥ 5) in the first 6 hours of life in order to identify subgroups at high risk prior to the need to initiate cooling.

  6. Heterogeneity of amplitude or continuous electroencephalography. [ Time Frame: Day of life 1 ]
    Determine the heterogeneity of the treatment effect across subgroups assessing the amplitude or continuous electroencephalography (abnormal background <30microvolts or absence of sleep-wake cycles) in the first 6 hours in order to identify subgroups at high risk prior to the need to initiate cooling.



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Ages Eligible for Study:   36 Weeks and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Term infants ≥ 36 weeks' gestation with evidence of both perinatal event fetal acidosis and encephalopathy on exam.
Criteria

Inclusion Criteria:

  • Infant ≥ 36 0/7 weeks with evidence of BOTH

    1. Perinatal depression as defined by NICHD based on at least one of the following; pH <7.00 in a cord gas or Base deficit ≥15 mmol/L in a gas (arterial or venous) obtained at <60 min of age, Apgar score <5 at 10 minutes, or Need for resuscitation at 10 minutes (i.e., chest compressions, or positive pressure respiratory support including endotracheal, mask ventilation, or CPAP).
    2. Mild encephalopathy, as defined by PRIME-study 1-6 hours after birth:

At least 1 of 6 Sarnat criteria is scored as a mild, moderate, or severe abnormality, and Fewer than 3 of 6 Sarnat criteria are scored as a moderate or severe abnormality

Exclusion Criteria:

  1. Birthweight <1800g (i.e., intrauterine growth restriction)
  2. Head circumference <30cm
  3. Confirmed clinical or EEG seizures in the first 6 hours of life
  4. Congenital malformation or genetic syndrome

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04621279


Contacts
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Contact: Lina Chalak, MD 214-648-3903 lina.chalak@utsouthwestern.edu
Contact: Pollieanna Sepulveda, BSN, RN 214-648-3698 pollieanna.sepulveda@utsouthwestern.edu

Sponsors and Collaborators
University of Texas Southwestern Medical Center
Nationwide Children's Hospital
University of California, San Francisco
Children's National Research Institute
Children's Hospital Los Angeles
Washington University School of Medicine
St. Louis University
University of Washington
Stanford University
Children's Hospital of Philadelphia
University of Utah Hospital
University of Pittsburgh Medical Center
Emory University
Children's Hospital Medical Center, Cincinnati
University College Cork
Investigators
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Principal Investigator: Lina Chalak, MD University of Texas Southwestern Medical Center
Publications:
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Responsible Party: Lina Chalak, PROFESSOR, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04621279    
Other Study ID Numbers: v1.1
First Posted: November 9, 2020    Key Record Dates
Last Update Posted: January 27, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lina Chalak, University of Texas Southwestern Medical Center:
mild HIE
neonatal encephalopathy
brain ischemia
brain hypoxia
Additional relevant MeSH terms:
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Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Central Nervous System Diseases
Nervous System Diseases
Hypoxia
Signs and Symptoms, Respiratory
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain