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| ID | Type | Description | Link |
|---|---|---|---|
| R01HD070792 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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Intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) are brain lesions that commonly occur in preterm infants and are well-recognized major contributors to long-term brain injury and related disabilities later in life. Despite its prevalence, long term consequences, and enormous medical and social costs, mechanisms of IVH and optimal strategies to prevent or treat its occurrence are poorly defined, especially for extremely premature infants. Only one medical therapy, prophylactic indomethacin during the first 3 days of life, has been shown to prevent or decrease the severity of IVH in preterm infants, but its use is limited by toxic side effects and debatable effects on long-term outcomes. Several small studies and case reports suggest that delayed umbilical cord-clamping (DCC) may also decrease the incidence of IVH in premature infants, but thus far these trials have indomethacin treatment mixed within their cord clamping protocols. The investigators are conducting a randomized, blinded investigation of 4 treatment groups: 1) Control (no intervention); 2) DCC alone; 3) Prophylactic indomethacin alone; 4) Combination of DCC/indomethacin, with respect to survival, IVH or PVL incidence and severity, neurodevelopmental outcomes, and relevant mechanistic effects. With the steady rise in extreme prematurity births and clear links of IVH to long-term disabilities there is a need to improve care for these patients. This multi- disciplinary project addresses an important medical problem for an understudied patient population, where the current practice has clear limitations.
The investigators will compare efficacy and safety of prophylactic indomethacin, DCC, and their combination, in affecting the incidence and severity of IVH/PVL in infants <30wks gestational age (primary outcome measure of 'fraction of survivors with no severe IVH or PVL' among the 4 groups), and longer term neurocognitive function. Other secondary endpoints and investigations include mechanistic effects of prophylactic indomethacin, DCC, and their combination (blood volume/circulatory status, inflammatory stress, progenitor cells) as well as defining relationships between clinical outcomes and mechanistic measurements among treatment groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| immediate cord clamp & placebo IV solution | Placebo Comparator | This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. |
|
| delay cord clamp & placebo IV solution | Experimental | A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. |
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| immediate cord clamp & indomethacin IV | Active Comparator | Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). |
|
| indomethacin iv & delayed cord clamp | Experimental | A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Indomethacin | Drug | indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL | determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age | within first 60 days of life |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Acute Kidney Injury | measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population). | first 60 days of life |
| Measure | Description | Time Frame |
|---|---|---|
| Hematological Status | hematocrit, ferritin, hemoglobin at various times during NICU stay | first 60 days of life |
| Inflammatory Stress | measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vicki Whitehead, RN | UK Section of Neonatology | Study Director |
| John Bauer, PhD | UK Department of Pediatrics | Principal Investigator |
| Hong Huang, MD-PhD | University of Kentucky Section of Neonatology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kentucky Childrens Hospital Neonatal Intensive Care Unit | Lexington | Kentucky | 40506 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Immediate Cord Clamp & Placebo IV Solution | This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | May 15, 2019 |
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| delay in umbilical cord clamp at birth | Procedure | provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) |
|
| placebo infusion | Drug | saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) |
|
| immediate cord clamp at birth | Procedure | no delay in umbilical cord clamp; <10sec (recorded in delivery note) |
|
| first 60 days of life |
| Circulating Progenitor Cell Subpopulations | measures of several progenitor cell subtypes in blood during the NICU stay | first 60 days of life |
| Neurocognitive Assessments at Post-NICU Followup | standardized neurocognitive assessments done at NICU graduate clinic. | up to 24 months of corrected gestational age |
| FG001 | Delay Cord Clamp & Placebo IV Solution | A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) |
| FG002 | Immediate Cord Clamp & Indomethacin IV | Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note) |
| FG003 | Indomethacin iv & Delayed Cord Clamp | A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Immediate Cord Clamp & Placebo IV Solution | This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note) |
| BG001 | Delay Cord Clamp & Placebo IV Solution | A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) |
| BG002 | Immediate Cord Clamp & Indomethacin IV | Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note) |
| BG003 | Indomethacin iv & Delayed Cord Clamp | A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) |
| 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 | Mean | Standard Deviation | weeks |
| |||||||||||||||
| Sex/Gender, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Birth Weight | Mean | Standard Deviation | grams |
|
| 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 | Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL | determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age | Posted | Number | percent of participants | within first 60 days of life |
|
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| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Acute Kidney Injury | measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population). | Posted | Number | participants | first 60 days of life |
| ||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Hematological Status | hematocrit, ferritin, hemoglobin at various times during NICU stay | Not Posted | first 60 days of life | Participants | ||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Inflammatory Stress | measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay | Not Posted | first 60 days of life | Participants | ||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Circulating Progenitor Cell Subpopulations | measures of several progenitor cell subtypes in blood during the NICU stay | Not Posted | first 60 days of life | Participants | ||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Neurocognitive Assessments at Post-NICU Followup | standardized neurocognitive assessments done at NICU graduate clinic. | Not Posted | up to 24 months of corrected gestational age | Participants |
First 60 days of life.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Immediate Cord Clamp & Placebo IV Solution | This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note) | 6 | 36 | 5 | 36 | 0 | 36 |
| EG001 | Delay Cord Clamp & Placebo IV Solution | A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) | 10 | 87 | 7 | 87 | 0 | 87 |
| EG002 | Immediate Cord Clamp & Indomethacin IV | Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note) | 2 | 41 | 3 | 41 | 0 | 41 |
| EG003 | Indomethacin iv & Delayed Cord Clamp | A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) | 6 | 92 | 10 | 92 | 0 | 92 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Necrotizing Enterocolitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Extreme Prematurity | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Free Air in Abdomen | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Septic Shock | Blood and lymphatic system disorders | Systematic Assessment |
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| Bowel Perforation | Gastrointestinal disorders | Systematic Assessment |
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| CMV | Infections and infestations | Systematic Assessment |
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| Multiorgan Failure | General disorders | Systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Research Protocol Manager/Clinical/UKHC | University of Kentucky | (859) 257-1000 | hong.huang@uky.edu |
| Oct 30, 2020 |
| Prot_SAP_ICF_000.pdf |
| ID | Term |
|---|---|
| D007969 | Leukomalacia, Periventricular |
| D001930 | Brain Injuries |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004678 | Encephalomalacia |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D007213 | Indomethacin |
| ID | Term |
|---|---|
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Female |
|
| Unknown |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note) |
| OG003 | Indomethacin iv & Delayed Cord Clamp | A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) |
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