[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100581807":3},{"organization":4,"outcomesModule":7,"designInfo":76,"detailedDescription":89,"studyPopulation":34,"armGroups":90,"interventions":103,"overallOfficials":113,"centralContacts":123,"locations":132,"responsibleParty":266,"collaborators":268,"id":297,"slug":298,"hasResults":299,"nctId":300,"briefTitle":301,"officialTitle":302,"acronym":303,"eligibilityCriteria":304,"healthyVolunteers":299,"sex":305,"minAge":34,"maxAge":306,"enrollmentInfo":307,"targetDuration":34,"studyType":310,"phases":311,"briefSummary":313,"conditions":314,"keywords":316,"overallStatus":135,"whyStopped":34,"lastUpdateSubmitDate":321,"lastUpdatePostDateStruct":322,"startDateStruct":325,"completionDateStruct":327,"leadSponsor":329,"locationsCount":330},{"fullName":5,"class":6},"NICHD Global Network for Women's and Children's Health","NETWORK",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":34},[9],{"measure":10,"description":11,"timeFrame":12},"Composite outcome, defined by the occurrence of any of the following:","All-cause infant mortality or moderate to severe neurodevelopmental impairment","18-22 months",[14,17,21,25,29,32,35,37,40,44,47,49,53,56,59,62,66,69,72,74],{"measure":15,"description":16,"timeFrame":12},"Secondary composite outcome, defined by the occurrence of any of the following:","All-cause infant mortality or severe neurodevelopmental impairment",{"measure":18,"description":19,"timeFrame":20},"All-cause neonatal mortality","Death from any cause to 28 days after delivery","28 days after delivery",{"measure":22,"description":23,"timeFrame":24},"All-cause infant mortality","Death from any cause before first birthday","12 months",{"measure":26,"description":27,"timeFrame":28},"All-cause mortality","Death from any cause","18 months",{"measure":30,"description":31,"timeFrame":12},"Time to all-cause mortality","Timespan from randomization to death from any cause",{"measure":33,"description":34,"timeFrame":12},"Severe neurodevelopmental impairment",null,{"measure":36,"description":34,"timeFrame":12},"Moderate neurodevelopmental impairment",{"measure":38,"description":39,"timeFrame":12},"Composite cognitive, language, and motor scores on the Bayley Scales of Infant and Toddler Development-Fourth Edition","Cognitive Scale on the Bayley Scales of Infant and Toddler Development - Fourth Edition\n\n\\- Scale ranges from 55-145 such that higher scores indicate a better cognitive outcome.\n\nLanguage Scale on the Bayley Scales of Infant and Toddler Development - Fourth Edition - Scale ranges from 45-155 such that higher scores indicate a better language outcome.\n\nMotor Scale on the Bayley Scales of Infant and Toddler Development - Fourth Edition\n\n\\- Scale ranges from 45-155 such that higher scores indicate a better motor outcome.",{"measure":41,"description":42,"timeFrame":43},"Hammersmith Infant Neurological Exam score","Ranges from 0 to 78 where higher scores indicate a better neurological outcome.","6 months",{"measure":45,"description":46,"timeFrame":24},"Global Scale for Early Development D-score and DAZ","Global Scale for Early Development D-score: Ranges from 0 to 100 where higher scores indicate a higher level of overall development.\n\nGlobal Scale for Early Development DAZ: Ranges from -5 to 5 where higher scores indicate a higher level of overall development.",{"measure":48,"description":46,"timeFrame":12},"Global Scale for Early Development Short Form D-score and DAZ",{"measure":50,"description":51,"timeFrame":52},"Acute kidney injury within the first postnatal week","Defined as an increase in serum creatinine of 0.3 mg\u002FdL or more on 2 measurements","Postnatal days 2-4",{"measure":54,"description":55,"timeFrame":12},"Manual blood pressure (systolic and diastolic)","Systolic and diastolic blood pressure taken using manual measurement",{"measure":57,"description":58,"timeFrame":12},"Hypertension","Based on the systolic blood pressure at the ≥95% for age related normative values",{"measure":60,"description":61,"timeFrame":12},"Serum creatinine","Measured using serum creatinine testing.",{"measure":63,"description":64,"timeFrame":65},"Serious adverse events (SAEs)","An SAE form will be completed for any event meeting the following criteria:\n\n* Results in participant death;\n* Is life-threatening;\n* Requires hospitalization or prolongs existing hospitalization;\n* Results in persistent or significant disability or incapacity;\n* Any other serious or unexpected AE that the study investigator(s) feels should be reported.","Discharge or 7 days after administration of the last study drug (whichever occurs first)",{"measure":67,"description":68,"timeFrame":65},"Adverse events of special interest (AESIs)","To include:\n\n* Clinically diagnosed seizures\n* Receipt of any antiepileptic drug\n* Seizures not controlled on one antiepileptic drug\n* Hypoglycemia (BG \\\u003C30 mg\u002FdL)\n* Hyperglycemia (BG \\>200 mg\u002FdL)\n* Heart rate \\[HR\\] \\>180 beats per minute \\[bpm\\] within 30 minutes of study drug administration\n* Necrotizing enterocolitis (NEC): as defined by feeding intolerance, bloody stool and abdominal distension",{"measure":70,"description":70,"timeFrame":71},"Length\u002Fheight and length\u002Fheight-for-age z-score","Birth, 1 month, 6 months, 12 months, and 18-22 months",{"measure":73,"description":73,"timeFrame":71},"Weight and weight-for-age z-score",{"measure":75,"description":75,"timeFrame":71},"Head circumference and Head circumference-for-age z-score",{"allocation":77,"interventionModel":78,"interventionModelDescription":79,"primaryPurpose":80,"observationalModel":34,"timePerspective":34,"maskingInfo":81},"RANDOMIZED","PARALLEL","1:1 individually randomized, parallel-arm, double-blind, placebo-controlled trial","TREATMENT",{"masking":82,"maskingDescription":83,"whoMasked":84},"QUADRUPLE","The protocol study team, international principal investigator (iPI), site staff and participants will be masked to the assigned treatment arm. Lab personnel will be masked to the assigned treatment arm until assays for samples collected after randomization are complete.",[85,86,87,88],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","Background: One million newborns die annually due to intrapartum-related events (formerly referred to as birth asphyxia). Among survivors, intrapartum related events often lead to organ dysfunction with lasting consequences, including severe morbidity and neurodevelopmental impairment (NDI). Newborns exposed to significant intrapartum-related events can have brain injury, referred to as hypoxic ischemic encephalopathy (HIE). HIE is routinely treated with therapeutic hypothermia. However, a recent multi-national randomized controlled trial demonstrated that therapeutic hypothermia increased mortality from HIE in some contexts. Therefore, there is an urgent, unmet public health need to develop effective strategies for the treatment of HIE to prevent morbidity and mortality. Caffeine, a low-cost, readily available medication is a promising strategy for treatment of HIE given its neuroprotective, anti-inflammatory, and anti-oxidative properties. Furthermore, caffeine might have physiologic benefits beyond HIE, because a single dose of a methylxanthine (caffeine's drug class) reduces acute kidney injury in infants with HIE in settings where therapeutic hypothermia is not available.\n\nObjective: To compare the incidence of all-cause mortality OR moderate to severe NDI at 18-22 months between neonates with HIE who are randomized to oral caffeine or placebo.\n\nHypothesis: Neonates with HIE who receive oral caffeine will have 10% lower incidence of all-cause mortality or moderate to severe NDI at 18-22 months compared to placebo.\n\nStudy Design: 1:1 individually randomized, parallel-arm, double-blind, placebo-controlled trial\n\nPopulation: ≥ 36 week gestation and ≥1800 grams liveborn neonates who meet both physiologic and neurologic criteria for moderate to severe HIE and live in the Global Network research sites\n\nIntervention: The intervention arm will receive one 20 mg\u002Fkg loading dose of caffeine given within 6 hours of delivery, followed by a daily dose of 10 mg\u002Fkg, given every 24 hours for 2 doses (total of 3 doses).\n\nComparison: The comparison arm will receive placebo using an identical dosing regimen.\n\nPrimary outcomes: All-cause mortality or moderate to severe NDI at 18-22 months of age\n\nSub-Studies: In conjunction with the CHIME Trial, we will embed 3 sub-studies to be conducted within subsets of CHIME participants. A sample will be chosen by convenience for each sub-study.\n\nPharmacokinetics Sub-study: For approximately 40 participants per Global Network research site, we will collect 2-3 blood samples during the birth hospitalization for pharmacokinetic (PK) analysis of caffeine. We will use a population PK approach to characterize the PK of infants with HIE, and to relate caffeine exposure to mortality or moderate to severe disability.\n\nNeuro-imaging Sub-Study: For participants who are born at or follow-up in a facility with the capability of performing ultra-low-field (ULF) magnetic resonance imaging (MRI), we will obtain ULF MRI brain images during the birth hospitalization and at the 6-month follow-up visit. We will relate the findings on ULF MRI to the severity of HIE at enrollment and to the neurodevelopmental outcomes.\n\nOmics Sub-Study: For participants for whom cord blood is available, we will obtain a sample of cord blood to be stored for future multi-omic analyses (e.g., genomic, transcriptomic, proteomic, and metabolomic). We will use multi-omics to identify molecular signatures associated with HIE.",[91,97],{"label":92,"type":93,"description":94,"interventionNames":95},"Caffeine citrate oral solution","EXPERIMENTAL","Participants randomized to the oral caffeine arm will receive a single 20 mg\u002Fkg loading dose of caffeine citrate administered enterally within 6 hours after delivery, followed by a 10 mg\u002Fkg dose every 24 hours for two additional doses.",[96],"Drug: Caffeine citrate oral solution",{"label":98,"type":99,"description":100,"interventionNames":101},"Oral placebo","PLACEBO_COMPARATOR","Participants randomized to the oral placebo arm will receive a single identical placebo administered enterally within 6 hours after delivery, followed by an identical placebo dose every 24 hours for two additional doses.",[102],"Drug: Oral placebo solution",[104,108],{"type":105,"name":92,"description":106,"armGroupLabels":107,"otherNames":34},"DRUG","Caffeine citrate oral solution will be used and administered by enteral route (oral or by gavage tube). The loading dose (20 mg\u002Fkg) will be administered once followed by daily doses of 10 mg per kg body weight every 24 hours for two doses. The study Standard Operating Procedures (SOPs) includes details regarding caffeine preparation based on the participant's body weight.",[92],{"type":105,"name":109,"description":110,"armGroupLabels":111,"otherNames":112},"Oral placebo solution","Identical placebo oral solution",[98],[98],[114,118,121],{"name":115,"affiliation":116,"role":117},"Melissa Bauserman, MD, MPH","University of North Carolina, Chapel Hill","PRINCIPAL_INVESTIGATOR",{"name":119,"affiliation":120,"role":117},"Elizabeth M McClure, PhD","RTI International",{"name":122,"affiliation":120,"role":117},"Denise C Babineau, PhD",[124,129],{"name":125,"role":126,"phone":127,"phoneExt":34,"email":128},"Laura Danielle Wagner, MPH","CONTACT","+1-919-541-6000","wagner@rti.org",{"name":130,"role":126,"phone":34,"phoneExt":34,"email":131},"Jennifer J Hemingway-Foday, MPH, MSW","hemingway@rti.org",[133,154,180,199,217,230,249],{"facility":134,"status":135,"city":136,"state":34,"zip":34,"country":137,"countryCode":138,"cosmosGeoPoint":139,"geoPoint":144,"contacts":145},"ICDDR,B","RECRUITING","Saidpur","Bangladesh","BD",{"type":140,"coordinates":141},"Point",[142,143],88.89169,25.77769,{"lat":143,"lon":142},[146,149,150,152],{"name":147,"role":126,"phone":34,"phoneExt":34,"email":148},"Rashidul Haque, MD","rhaque@icddrb.org",{"name":147,"role":117,"phone":34,"phoneExt":34,"email":34},{"name":151,"role":117,"phone":34,"phoneExt":34,"email":34},"SK Masum Billah",{"name":153,"role":117,"phone":34,"phoneExt":34,"email":34},"William A Petri, MD",{"facility":155,"status":156,"city":157,"state":34,"zip":34,"country":158,"countryCode":159,"cosmosGeoPoint":160,"geoPoint":164,"contacts":165},"Kinshasa School of Public Health","NOT_YET_RECRUITING","Kinshasa","Democratic Republic of the Congo","CD",{"type":140,"coordinates":161},[162,163],15.31357,-4.32758,{"lat":163,"lon":162},[166,169,172,173,174,177,178],{"name":167,"role":126,"phone":34,"phoneExt":34,"email":168},"Antoinette Tshefu, MD, PhD, MPH","antotshe@yahoo.com",{"name":170,"role":126,"phone":34,"phoneExt":34,"email":171},"Adrien Lokangaka, MD, MPH","adrinloks@gmail.com",{"name":167,"role":117,"phone":34,"phoneExt":34,"email":34},{"name":115,"role":117,"phone":34,"phoneExt":34,"email":34},{"name":175,"role":176,"phone":34,"phoneExt":34,"email":34},"Jackie Patterson, MD, MPH","SUB_INVESTIGATOR",{"name":170,"role":176,"phone":34,"phoneExt":34,"email":34},{"name":179,"role":176,"phone":34,"phoneExt":34,"email":34},"Keia Sanderson, MD, MSCR",{"facility":181,"status":135,"city":182,"state":34,"zip":34,"country":183,"countryCode":184,"cosmosGeoPoint":185,"geoPoint":189,"contacts":190},"Institute of Nutrition of Central America And Panama (INCAP)","Chimaltenango","Guatemala","GT",{"type":140,"coordinates":186},[187,188],-90.8216,14.65881,{"lat":188,"lon":187},[191,194,195,197],{"name":192,"role":126,"phone":34,"phoneExt":34,"email":193},"Manolo Mazariegos, MD, MPH","mmaziergos@incap.org",{"name":192,"role":117,"phone":34,"phoneExt":34,"email":34},{"name":196,"role":117,"phone":34,"phoneExt":34,"email":34},"Nancy F Krebs, MD",{"name":198,"role":176,"phone":34,"phoneExt":34,"email":34},"Edwin J Asturias, MD",{"facility":200,"status":156,"city":201,"state":34,"zip":34,"country":202,"countryCode":203,"cosmosGeoPoint":204,"geoPoint":208,"contacts":209},"KLE University's J N Medical College","Belagavi","India","IN",{"type":140,"coordinates":205},[206,207],74.50447,15.85212,{"lat":207,"lon":206},[210,213,215],{"name":211,"role":126,"phone":34,"phoneExt":34,"email":212},"Shivaprasad S. Goudar, MD, MHPE","sgoudar@jnmc.edu",{"name":214,"role":117,"phone":34,"phoneExt":34,"email":34},"Shivaprasad S Goudar, MD, MHPE",{"name":216,"role":117,"phone":34,"phoneExt":34,"email":34},"Richard J Derman, MD, MPH",{"facility":218,"status":156,"city":219,"state":34,"zip":34,"country":202,"countryCode":203,"cosmosGeoPoint":220,"geoPoint":224,"contacts":225},"Lata Medical Research Foundation","Nagpur",{"type":140,"coordinates":221},[222,223],79.08491,21.14631,{"lat":223,"lon":222},[226,229],{"name":227,"role":126,"phone":34,"phoneExt":34,"email":228},"Archana Patel, MD, DNB, MSCE, PhD","Dr_apatel@yahoo.com",{"name":227,"role":117,"phone":34,"phoneExt":34,"email":34},{"facility":231,"status":156,"city":232,"state":34,"zip":34,"country":233,"countryCode":234,"cosmosGeoPoint":235,"geoPoint":239,"contacts":240},"Aga Khan University","Karachi","Pakistan","PK",{"type":140,"coordinates":236},[237,238],67.0104,24.8608,{"lat":238,"lon":237},[241,244,245,247],{"name":242,"role":126,"phone":34,"phoneExt":34,"email":243},"Sarah Saleem, MD","sarah.saleem@aku.edu",{"name":242,"role":117,"phone":34,"phoneExt":34,"email":34},{"name":246,"role":117,"phone":34,"phoneExt":34,"email":34},"Robert L Goldenberg, MD",{"name":248,"role":176,"phone":34,"phoneExt":34,"email":34},"Blair Wylie, MD",{"facility":250,"status":135,"city":251,"state":34,"zip":34,"country":252,"countryCode":253,"cosmosGeoPoint":254,"geoPoint":258,"contacts":259},"University Teaching Hospital","Lusaka","Zambia","ZM",{"type":140,"coordinates":255},[256,257],28.28713,-15.40669,{"lat":257,"lon":256},[260,263,264],{"name":261,"role":126,"phone":34,"phoneExt":34,"email":262},"Elwyn Chomba, MBChB, DCH, MRCP","echomba@zamnet.zm",{"name":261,"role":117,"phone":34,"phoneExt":34,"email":34},{"name":265,"role":117,"phone":34,"phoneExt":34,"email":34},"Wally A. Carlo, MD",{"type":267,"investigatorFullName":34,"investigatorTitle":34,"investigatorAffiliation":34,"oldNameTitle":34,"oldOrganization":34},"SPONSOR",[269,271,272,273,275,277,278,280,283,285,287,289,291,293,295],{"name":120,"class":270},"OTHER",{"name":116,"class":270},{"name":155,"class":270},{"name":274,"class":270},"Institute of Nutrition of Central America and Panama",{"name":276,"class":270},"Lata Medical Research Foundation, Nagpur",{"name":231,"class":270},{"name":279,"class":270},"University Teaching Hospital, Lusaka, Zambia",{"name":281,"class":282},"KLE Academy of Higher Education and Research (Deemed- to- be-University), Jawaharlal Nehru Medical College (JNMC), Belagavi, India","UNKNOWN",{"name":284,"class":270},"Bill and Melinda Gates Foundation",{"name":286,"class":270},"University of Virginia",{"name":288,"class":270},"University of Alabama at Birmingham",{"name":290,"class":270},"Thomas Jefferson University",{"name":292,"class":270},"Columbia University",{"name":294,"class":270},"University of Colorado, Denver",{"name":296,"class":270},"International Centre for Diarrhoeal Disease Research, Bangladesh","100581807","phase-3-caffeine-for-hypoxic-ischemic-encephalopathy-100581807",false,"NCT06855108","Caffeine for Hypoxic Ischemic Encephalopathy","Caffeine for Hypoxic Ischemic Encephalopathy (CHIME Trial)","CHIME","Participant Inclusion Criteria:\n\nInfants who meet all the following criteria are eligible for enrollment as study participants:\n\n1. Liveborn infants ≥36 weeks\n2. Birth weight ≥1800 grams\n3. Meets physiologic criteria for moderate to severe HIE, defined as meeting either of the following two criteria:\n\n   1. Criterion #1: Severe acidosis, defined as an umbilical cord sample or neonatal serum sample within one hour after birth demonstrating any of following criteria:\n\n      * pH \\\u003C7.0; or\n      * Base Deficit ≥16 mmol\u002FL; or\n      * Lactate \\>8 mmol\u002FL.\n   2. Criterion #2: Participant must meet all of the following three criteria:\n\n   i. Moderate acidosis, defined as an umbilical cord sample or neonatal serum sample within one hour after birth demonstrating any of following criteria:\n   * POC pH 7.0-7.15; or\n   * Base Deficit 10.0-15.9 mmol\u002FL; or\n   * Lactate 6-8 mmol\u002FL.\n\n   ii. Evidence of an acute perinatal event (i.e., placental abruption, intrapartum hemorrhage, cord prolapse, severe fetal heart rate abnormality, uterine rupture).\n\n   iii. Any of the following criteria:\n   * 10-minute Apgar \\\u003C5; or\n   * Need for assisted ventilation initiated at birth and continued for ≥10 minutes\n4. Meets neurologic criteria for moderate to severe HIE, defined as a physical exam conducted between one and six hours after birth that meets either of the following criteria:\n\n   1. Moderate to severe encephalopathy in at least three out of six modified Sarnat categories (level of consciousness, spontaneous activity, muscle tone, posture, primitive reflexes, autonomic function); or\n   2. A clinical diagnosis of seizure in the first six hours after birth.\n\nParticipant Exclusion Criteria:\n\nInfants who meet any of the following criteria are not eligible for enrollment as study participants:\n\n1. Home births\n2. Infants who cannot be enrolled, randomized and receive study medication within 6 hours post-delivery\n3. Infants with a recognized major congenital anomaly or genetic syndrome that would affect their neurodevelopment.\n4. Infants for whom medical care will not be provided based on the severity of their condition or any other condition that would preclude participation per clinical judgement.\n5. Infant has received therapeutic hypothermia or there is a clinical plan to initiate active or passive hypothermia for the infant.\n6. Infants who will be unavailable to complete follow-up visits.\n7. Infants who have received caffeine after delivery.\n8. Infants whom the health care team deem ineligible for the study based on likelihood to receive caffeine outside of the study protocol.\n9. Enrollment in another trial that will impact participation in this trial.","ALL","6 Hours",{"count":308,"type":309},830,"ESTIMATED","INTERVENTIONAL",[312],"PHASE3","CHIME is a randomized, parallel-arm, double-blind, placebo-controlled trial focused on infants with hypoxic ischemic encephalopathy (HIE). The trial will recruit neonates who are diagnosed with HIE within six hours after birth based on physiologic criteria (acidosis noted on an umbilical cord or early \\[\\\u003C1 hour\\] postnatal blood sample) and neurologic criteria (modified Sarnat exam consistent with encephalopathy). Following informed consent, and by six hours after birth, neonates with HIE will be randomized to one of two treatment arms and subsequently receive one 20 mg\u002Fkg dose of oral caffeine followed by two additional 10 mg\u002Fkg doses at 24-hour intervals or placebo of the same regimen (three total doses).\n\nThe goal of this clinical trial is to compare the incidence of all-cause mortality OR moderate to severe neurodevelopmental impairment (NDI) at 18-22 months between neonates with HIE who are randomized to oral caffeine or placebo. Our hypothesis is that neonates with HIE who receive oral caffeine will have 10% lower incidence of all-cause mortality or moderate to severe NDI at 18-22 months compared to placebo.",[315],"Hypoxic Ischemic Encephalopathy (HIE)",[317,318,319,320],"Caffeine","Hypoxic Ischemic Encephalopathy","HIE","AKI","2026-06-19",{"date":323,"type":324},"2026-06-24","ACTUAL",{"date":326,"type":324},"2026-04-08",{"date":328,"type":309},"2030-07",{"name":5,"class":6},7]