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| ID | Type | Description | Link |
|---|---|---|---|
| U10HD021364 | U.S. NIH Grant/Contract | View source | |
| U10HD021373 | U.S. NIH Grant/Contract | View source | |
| U10HD021385 | U.S. NIH Grant/Contract | View source | |
| U10HD027851 | U.S. NIH Grant/Contract | View source | |
| U10HD027853 | U.S. NIH Grant/Contract | View source | |
| U10HD027856 | U.S. NIH Grant/Contract | View source | |
| U10HD027871 | U.S. NIH Grant/Contract | View source | |
| U10HD027880 | U.S. NIH Grant/Contract | View source | |
| U10HD027904 | U.S. NIH Grant/Contract | View source | |
| U10HD034216 | U.S. NIH Grant/Contract | View source | |
| U10HD036790 | U.S. NIH Grant/Contract | View source | |
| U10HD040492 | U.S. NIH Grant/Contract | View source | |
| U10HD040689 | U.S. NIH Grant/Contract | View source | |
| U10HD053089 | U.S. NIH Grant/Contract | View source | |
| U10HD053109 | U.S. NIH Grant/Contract | View source | |
| U10HD053119 | U.S. NIH Grant/Contract | View source | |
| U10HD053124 | U.S. NIH Grant/Contract | View source | |
| UL1RR024139 | U.S. NIH Grant/Contract | View source | |
| UL1RR024979 | U.S. NIH Grant/Contract | View source | |
| UL1RR025008 | U.S. NIH Grant/Contract | View source | |
| UL1RR025744 | U.S. NIH Grant/Contract | View source | |
| UL1RR025747 | U.S. NIH Grant/Contract | View source | |
| UL1RR025761 | U.S. NIH Grant/Contract | View source | |
| UL1RR025764 | U.S. NIH Grant/Contract | View source | |
| U10HD068284 | U.S. NIH Grant/Contract | View source | |
| U10HD068278 | U.S. NIH Grant/Contract | View source | |
| U10HD068270 | U.S. NIH Grant/Contract | View source | |
| U10HD068263 | U.S. NIH Grant/Contract | View source | |
| U10HD068244 | U.S. NIH Grant/Contract | View source |
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The trial closed for emerging safety profile and futility analysis and will not resume.
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| Name | Class |
|---|---|
| National Center for Research Resources (NCRR) | NIH |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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The Optimizing Cooling trial will compare four whole-body cooling treatments for infants born at 36 weeks gestational age or later with hypoxic-ischemic encephalopathy: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. The objective of this study is to evaluate whether whole-body cooling initiated at less than 6 hours of age and continued for 120 hours and/or a depth at 32.0°C in will reduce death and disability at 18-22 months corrected age.
Hypoxic-ischemic encephalopathy (HIE) is a rare, but life-threatening condition characterized by brain injury due to asphyxia diagnosed at or shortly after birth. According to the World Health Organization, more than 722,000 children died from birth asphyxia and birth trauma worldwide in 2004. An estimated 50-75 percent of infants with severe (stage 3) HIE will die, with 55 percent of these deaths occurring in the first month. Up to 80 percent of infants who survive stage 3 HIE develop significant long-term disabilities, including intellectual disabilities, epilepsy, and cerebral palsy with hemiplegia, paraplegia, or quadriplegia; 10-20 percent develop moderately serious disabilities; and up to 10 percent are normal.
Previous studies have shown treatment with hypothermia to be an effective therapy for HIE. Currently, infants diagnosed with HIE at less than six hours of age are given whole-body cooling, decreasing their core body temperature to 33.5°C (93.2° Fahrenheit) for a period 72 hours using a cooling blanket. This treatment appears to protect the brain, decreasing the rate of death and disability and improving the chances of survival and neurodevelopmental outcomes at 18 months correct age. But additional trials are needed to help define the most effective cooling strategies.
The Optimizing Cooling trial will examine whether cooling for a longer time period and/or to a lower temperature will improve the chance of survival and neurodevelopmental outcomes at 18-22 months corrected age. Eligible infants with HIE will be placed in one of four cooling groups: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. Infants will be monitored closely and receive the care of the Neonatal Intensive Care Unit (NICU).
Infants enrolled in the study will be placed on a cooling blanket - the same type of blanket children's hospitals use in the NICU, in operating rooms during surgeries, and to cool children with high fevers. Each infant will be cooled according to the study group he or she is assigned to. During cooling, the infant's temperature will be very closely monitored by continuous esophageal (core)temperature readings. This will be done by placing a soft, narrow, flexible plastic tube into the infant's nose and down to just above the stomach. Skin temperatures will also be monitored closely. At the end of the assigned period of cooling, the infant will be slowly re-warmed until a normal core temperature of 36.5 to 37.0°C (97.7 to 98.6°C) is reached.
Infants will be examined at 18-22 months corrected age to assess their neurodevelopmental outcomes.
Secondary Studies include:
A. Using aEEG to 1)predict mortality or moderate to severe disability at 18-22 months in term infants with HIE treated with systemic hypothermia and 2) to record electrical seizure activity to compare rewarming initiated at 72 hours and later rewarming that is initiated at 120 hours.
B. Secondary Study includes determining an association between MRI detectable injury and neurodevelopment at 18-22 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 33.5°C for 72 hours | Active Comparator | Target Temp: 33.5°C Duration: 72 hrs |
|
| 33.5°C for 120 hours | Experimental | Target Temp: 33.5°C Duration: 120 hrs |
|
| 32.0°C for 72 hours | Experimental | Target Temp: 32.0°C Duration: 72 hrs |
|
| 32.0°C for 120 hours | Experimental | Target Temp: 32.0°C Duration:120 hrs |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Whole-body Cooling | Procedure | Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| Measure | Description | Time Frame |
|---|---|---|
| Death or Moderate to Severe Disability | Death includes any mortality prior to follow up at 18-22 months. Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. | Birth to 22 months corrected age |
| Measure | Description | Time Frame |
|---|---|---|
| Death | Death includes any mortality prior to follow up at 18-22 months. | Birth to 22 months corrected age |
| Level of Disability Among Survivors | Among survivors number of normal infants and infants with mild, moderate, and severe disability Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge. |
| Measure | Description | Time Frame |
|---|---|---|
| Severe Neonatal Brain Abnormalities | Total hemispheric devastation based on MRI taken between 7-14 days of life | 7-14 days of life |
Inclusion Criteria:
Eligibility will be determined in a stepped process:
All infants with a gestational age ≥ 36 weeks will be screened for study entry if they are admitted to the NICU with a diagnosis of fetal acidosis, perinatal asphyxia, neonatal depression or encephalopathy.
Infants will be eligible if:
Once these criteria are met, eligible infants will have a standardized neurological examination performed by a certified physician examiner. Infants will be candidates for the study when encephalopathy or seizures are present. For this study, encephalopathy is defined as the presence of 1 or more signs in 3 of the following 6 categories:
Eligible infants from multiple births will be enrolled in the same arm of the study.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Seetha Shankaran, MD | Wayne State University | Study Chair |
| Abbot R Laptook, MD | Brown University, Women & Infants Hospital of Rhode Island | Principal Investigator |
| Michele C Walsh, MD MS | Case Western Reserve University, Rainbow Babies and Children's Hospital | Principal Investigator |
| Ronald N. Goldberg, MD | Duke University | Principal Investigator |
| Barbara J. Stoll, MD | Emory University | Principal Investigator |
| Brenda B. Poindexter, MD MS | Indiana University | Principal Investigator |
| Abhik Das, PhD | RTI International | Principal Investigator |
| Krisa P. Van Meurs, MD | Stanford University | Principal Investigator |
| Kurt Schibler, MD | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| University of California - Los Angeles |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39960680 | Derived | Shankaran S, Laptook AR, Guimaraes C, Murnick J, McDonald SA, Das A, Petrie Huitema CM, Pappas A, Higgins RD, Hintz SR, Zaterka-Baxter KM, Van Meurs KP, Sokol GM, Chalak LF, Colaizy TT, Devaskar U, Tyson JE, Reynolds AM, DeMauro SB, Sanchez PJ, Laughon MM, Carlo WA, Watterberg K, Puopolo KM, Hibbs AM, Hamrick SEG, Cotten CM, Barks J, Poindexter BB, Truog WE, D'Angio CT; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. NICHD Magnetic Resonance Brain Imaging Score in Term Infants With Hypoxic-Ischemic Encephalopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. 2025 Apr 1;179(4):383-395. doi: 10.1001/jamapediatrics.2024.6209. | |
| 35835616 |
| Label | URL |
|---|---|
| Neonatal Research Network website | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| Publication | View IPD |
All eligible infants with consent were randomized to one of four treatment arms/groups.
1261 infants assessed for eligibility. 897 were excluded for not meeting eligibility criteria (N=747) or not having parental or physician consent (N=150).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 33.5°C for 72 Hours | Target Temp: 33.5°C Duration: 72 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| FG001 | 32.0°C for 72 Hours |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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|
| Follow up at 18-22 months corrected age |
| Withdrawal of Care | Number of infants for whom aggressive care is withdrawn | Birth through hospital discharge, average 22 days. |
| Clinical Neonatal Seizures | Documented seizures during hospital course | Through death, discharge, or transfer |
| Bayley Cognitive Score | Bayley Scale of Infant Development Composite Cognitive Score. The total composite score is reported, ranging from the lowest score of 55 to the highest score of 145. Lower values specify worse outcome. | Follow up at 18-22 months corrected age |
| Cerebral Palsy | Follow up at 18-22 months corrected age |
| Level of Disability Among Survivors, by Level of HIE | Among survivors, number of normal infants and infants with mild, moderate and severe disability Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge. | Follow up at 18-22 months corrected age |
| Visual Impairment | Visual impairment is defined as bilateral blindness with some/no useful vision | Follow up at 18-22 months corrected age |
| Hearing Impairment | Hearing impairment is defined as hearing impairment despite amplification | Follow up at 18-22 months corrected age |
| Multiple Disabilities | Multiple disabilities is defined as two or more of the following 5 components: disabling CP, GMFCS level 3-5, Bayley cognitive score < 70, blindness, or deafness. | Follow up at 18-22 months corrected age |
| Multiorgan Dysfunction | The data needed for this analysis are not collected directly, and will not be analyzed as the study was terminated early and no funds available to complete this complex analysis. The data for this study will be stored at the NICHD-DASH for investigators. | Until death, discharge, or transfer |
| Waldemar A. Carlo, MD |
| University of Alabama at Birmingham |
| Principal Investigator |
| Edward F. Bell, MD | University of Iowa | Principal Investigator |
| Kristi L. Watterberg, MD | University of New Mexico | Principal Investigator |
| Pablo J. Sanchez, MD | University of Texas, Southwestern Medical Center at Dallas | Principal Investigator |
| Kathleen A. Kennedy, MD MPH | The University of Texas Health Science Center, Houston | Principal Investigator |
| William Truog, MD | Children's Mercy Hospital Kansas City | Principal Investigator |
| Barbara Schmidt, MD, MSc | University of Pennsylvania | Principal Investigator |
| Carl D'Angio, MD | University of Rochester | Principal Investigator |
| Uday Devaskar, MD | University of California, Los Angeles | Principal Investigator |
| Leif Nelin, MD | Research Institute at Nationwide Children's Hospital | Principal Investigator |
| Los Angeles |
| California |
| 90025 |
| United States |
| Stanford University | Palo Alto | California | 94304 | United States |
| Emory University | Atlanta | Georgia | 30303 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| Wayne State University | Detroit | Michigan | 48201 | United States |
| Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| University of New Mexico | Albuquerque | New Mexico | 87131 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| RTI International | Durham | North Carolina | 27705 | United States |
| Duke University | Durham | North Carolina | 27710 | United States |
| Cincinnati Children's Medical Center | Cincinnati | Ohio | 45267 | United States |
| Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland | Ohio | 44106 | United States |
| Research Institute at Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Univeristy of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Brown University, Women & Infants Hospital of Rhode Island | Providence | Rhode Island | 02905 | United States |
| University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | 75235 | United States |
| University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| Derived |
| Bonifacio SL, Chalak LF, Van Meurs KP, Laptook AR, Shankaran S. Neuroprotection for hypoxic-ischemic encephalopathy: Contributions from the neonatal research network. Semin Perinatol. 2022 Nov;46(7):151639. doi: 10.1016/j.semperi.2022.151639. Epub 2022 Jun 10. |
| 35296895 | Derived | Shukla VV, Bann CM, Ramani M, Ambalavanan N, Peralta-Carcelen M, Hintz SR, Higgins RD, Natarajan G, Laptook AR, Shankaran S, Carlo WA. Predictive Ability of 10-Minute Apgar Scores for Mortality and Neurodevelopmental Disability. Pediatrics. 2022 Apr 1;149(4):e2021054992. doi: 10.1542/peds.2021-054992. |
| 34882200 | Derived | Chalak LF, Pappas A, Tan S, Das A, Sanchez PJ, Laptook AR, Van Meurs KP, Shankaran S, Bell EF, Davis AS, Heyne RJ, Pedroza C, Poindexter BB, Schibler K, Tyson JE, Ball MB, Bara R, Grisby C, Sokol GM, D'Angio CT, Hamrick SEG, Dysart KC, Cotten CM, Truog WE, Watterberg KL, Timan CJ, Garg M, Carlo WA, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Association Between Increased Seizures During Rewarming After Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy and Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study. JAMA Neurol. 2021 Dec 1;78(12):1484-1493. doi: 10.1001/jamaneurol.2021.3723. |
| 33986149 | Derived | Ambalavanan N, Shankaran S, Laptook AR, Carper BA, Das A, Carlo WA, Cotten CM, Duncan AF, Higgins RD; EUNICE KENNEDY SHRIVER NICHD NEONATAL RESEARCH NETWORK. Early Determination of Prognosis in Neonatal Moderate or Severe Hypoxic-Ischemic Encephalopathy. Pediatrics. 2021 Jun;147(6):e2020048678. doi: 10.1542/peds.2020-048678. Epub 2021 May 13. |
| 28672318 | Derived | Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Huitema CMP, Grisby C, Devaskar U, Ehrenkranz RA, Harmon HM, Chalak LF, DeMauro SB, Garg M, Hartley-McAndrew ME, Khan AM, Walsh MC, Ambalavanan N, Brumbaugh JE, Watterberg KL, Shepherd EG, Hamrick SEG, Barks J, Cotten CM, Kilbride HW, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):57-67. doi: 10.1001/jama.2017.7218. |
| 27450203 | Derived | Pedroza C, Tyson JE, Das A, Laptook A, Bell EF, Shankaran S; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Advantages of Bayesian monitoring methods in deciding whether and when to stop a clinical trial: an example of a neonatal cooling trial. Trials. 2016 Jul 22;17(1):335. doi: 10.1186/s13063-016-1480-4. |
| 25536254 | Derived | Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Grisby C, Huitema CM, Garg M, Ehrenkranz RA, Shepherd EG, Chalak LF, Hamrick SE, Khan AM, Reynolds AM, Laughon MM, Truog WE, Dysart KC, Carlo WA, Walsh MC, Watterberg KL, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. JAMA. 2014 Dec 24-31;312(24):2629-39. doi: 10.1001/jama.2014.16058. |
| 24524452 | Derived | Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008. |
Target Temp: 32.0°C Duration: 72 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| FG002 | 33.5°C for 120 Hours | Target Temp: 33.5°C Duration: 120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| FG003 | 32.0°C for 120 Hours | Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| Died Prior to Discharge |
|
| Died After Discharge |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 33.5°C for 72 Hours | Target Temp: 33.5°C Duration: 72 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| BG001 | 32.0°C for 72 Hours | Target Temp: 32.0°C Duration: 72 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| BG002 | 33.5°C for 120 Hours | Target Temp: 33.5°C Duration: 120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| BG003 | 32.0°C for 120 Hours | Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at Randomization | Data was missing for one participant. | Mean | Standard Deviation | hours |
| ||||||||
| Sex/Gender, Customized | Count of Participants | Participants |
| |||||||||||
| Race/Ethnicity, Customized | Data was missing for six participants. | Count of Participants | Participants |
| ||||||||||
| Birthweight | Data was missing for one participant. | Mean | Standard Deviation | grams |
| |||||||||
| Level of encephalopathy | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Death or Moderate to Severe Disability | Death includes any mortality prior to follow up at 18-22 months. Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. | Includes all deaths and all infants followed at 18-22 months. Does not include 17 infants lost to follow up. | Posted | Count of Participants | Participants | Birth to 22 months corrected age |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Death | Death includes any mortality prior to follow up at 18-22 months. | Includes all deaths and all infants followed at 18-22 months. Does not include 17 infants lost to follow up. | Posted | Count of Participants | Participants | Birth to 22 months corrected age |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Level of Disability Among Survivors | Among survivors number of normal infants and infants with mild, moderate, and severe disability Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge. | Includes all infants followed at 18-22 months except for 6 infants who could not be distinguished between normal and mild. Does not include 17 infants lost to follow up or 56 deaths | Posted | Count of Participants | Participants | Follow up at 18-22 months corrected age |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Withdrawal of Care | Number of infants for whom aggressive care is withdrawn | Posted | Count of Participants | Participants | Birth through hospital discharge, average 22 days. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Clinical Neonatal Seizures | Documented seizures during hospital course | Posted | Count of Participants | Participants | Through death, discharge, or transfer |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Bayley Cognitive Score | Bayley Scale of Infant Development Composite Cognitive Score. The total composite score is reported, ranging from the lowest score of 55 to the highest score of 145. Lower values specify worse outcome. | Infants who survived and were followed at 18-22 months | Posted | Median | Inter-Quartile Range | scores on a scale | Follow up at 18-22 months corrected age |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cerebral Palsy | Infants who survived and were followed at 18-22 months | Posted | Count of Participants | Participants | Follow up at 18-22 months corrected age |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Level of Disability Among Survivors, by Level of HIE | Among survivors, number of normal infants and infants with mild, moderate and severe disability Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge. | Includes all infants followed at 18-22 months, except for 6 infants who could not be distinguished between normal and mild. Does not include 17 infants lost to follow up or 56 deaths. | Posted | Count of Participants | Participants | Follow up at 18-22 months corrected age |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Visual Impairment | Visual impairment is defined as bilateral blindness with some/no useful vision | Infants who survived and were followed at 18-22 months | Posted | Count of Participants | Participants | Follow up at 18-22 months corrected age |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Hearing Impairment | Hearing impairment is defined as hearing impairment despite amplification | Infants who survived and were followed at 18-22 months | Posted | Count of Participants | Participants | Follow up at 18-22 months corrected age |
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| Secondary | Multiple Disabilities | Multiple disabilities is defined as two or more of the following 5 components: disabling CP, GMFCS level 3-5, Bayley cognitive score < 70, blindness, or deafness. | Infants who survived and were followed at 18-22 months | Posted | Count of Participants | Participants | Follow up at 18-22 months corrected age |
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| Secondary | Multiorgan Dysfunction | The data needed for this analysis are not collected directly, and will not be analyzed as the study was terminated early and no funds available to complete this complex analysis. The data for this study will be stored at the NICHD-DASH for investigators. | No patients were analyzed for this outcome as the study was terminated early and no additional funds available to complete this complex analysis. | Posted | Until death, discharge, or transfer |
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| Other Pre-specified | Severe Neonatal Brain Abnormalities | Total hemispheric devastation based on MRI taken between 7-14 days of life | Note that 66 infants are not included (total N for OC study=364); 49 were excluded due to lack of MRI of adequate quality, 16 due to missing primary outcome, and 1 due to genetic abnormality. | Posted | Count of Participants | Participants | 7-14 days of life |
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During study intervention period: 72 or 120 hours from baseline, based on treatment arm
17 infants lost to follow up were excluded from the All-Cause Mortality table. Mortality cannot be assessed for infants lost to follow up.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 33.5°C for 72 Hours | Target Temp: 33.5°C Duration: 72 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. | 8 | 92 | 10 | 95 | 5 | 95 |
| EG001 | 32.0°C for 72 Hours | Target Temp: 32.0°C Duration: 72 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. | 15 | 84 | 15 | 90 | 3 | 90 |
| EG002 | 33.5°C for 120 Hours | Target Temp: 33.5°C Duration: 120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. | 18 | 93 | 11 | 96 | 6 | 96 |
| EG003 | 32.0°C for 120 Hours | Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. | 15 | 78 | 23 | 83 | 9 | 83 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death during intervention | Nervous system disorders | Systematic Assessment |
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| Cardiac Arrythmia | Cardiac disorders | Systematic Assessment |
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| Thrombosis | Nervous system disorders | Systematic Assessment |
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| Major Bleeding | Nervous system disorders | Systematic Assessment |
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| Other | General disorders | Systematic Assessment | Other Serious Adverse Events |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Metabolic acidosis developing >3 hours after initiation of intervention and persisting >3 hours | General disorders | Systematic Assessment |
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| Alteration of Skin Integrity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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This RCT was stopped for safety and futility reasons by the Data Safety and Monitoring Committee so did not enroll the target number of participants needed to achieve target power and statistically reliable results.
Investigators must adhere to the Neonatal Research Network Publication policies.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Seetha Shankaran | Wayne State University | (313) 745-1436 | sshankar@med.wayne.edu |
| ID | Term |
|---|---|
| D002534 | Hypoxia, Brain |
| D020925 | Hypoxia-Ischemia, Brain |
| D007035 | Hypothermia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002545 | Brain Ischemia |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001832 | Body Temperature Changes |
Not provided
Not provided
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| Female |
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| Ambiguous |
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| White |
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| Other |
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33.5°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group) |
| Risk Ratio (RR) |
| 1.21 |
| 2-Sided |
| 95 |
| 0.78 |
| 1.87 |
| Superiority |
Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations |
| 32.0°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group) | Risk Ratio (RR) | 0.85 | 2-Sided | 95 | 0.53 | 1.35 | Superiority | Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations |
Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
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| OG002 | 33.5°C for 120 Hours | Target Temp: 33.5°C Duration: 120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| OG003 | 32.0°C for 120 Hours | Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
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| OG003 |
| 32.0°C for 120 Hours |
Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
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| OG002 | 33.5°C for 120 Hours | Target Temp: 33.5°C Duration: 120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
| OG003 | 32.0°C for 120 Hours | Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
|
|
Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
|
|
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Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
|
|
|
| 32.0°C for 120 Hours |
Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
|
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| OG003 | 32.0°C for 120 Hours | Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
|
| OG003 | 32.0°C for 120 Hours | Target Temp: 32.0°C Duration:120 hrs Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours. |
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| Mild disability |
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| Moderate disability |
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| Severe disability |
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| Title | Measurements |
|---|---|
| Normal |
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| Mild disability |
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| Moderate disability |
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| Severe disability |
|