Clinical trial NCT02221219: Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury
Official title: Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Intraventricular Hemorrhage
Periventricular Leukomalacia
Brain Injury
Renal Injury
Keywords: infant
brain injury
renal
indomethacin
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2014-08-20
Enrollment: 256
Sex: ALL
Minimum age (years): 24
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* pregnant women admitted \>24weeks and \<30weeks gestational age,
* in-hospital birth (allowing for cord clamp randomization)

Exclusion Criteria:

* preterm infant \<24weeks or \>30weeks at birth
* maternal risks identified by obstetrician
* fetal risks identified by obstetrician
* any congenital abnormality of newborn infant
* placental abruption/placental previa
* delivery less than 2hrs from consenting to study participation

Primary outcomes:
measure: Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL
timeFrame: within first 60 days of life
Secondary outcomes:
measure: Number of Participants With Acute Kidney Injury
timeFrame: first 60 days of life
Other outcomes:
measure: Hematological Status
timeFrame: first 60 days of life
measure: Inflammatory Stress
timeFrame: first 60 days of life
measure: Circulating Progenitor Cell Subpopulations
timeFrame: first 60 days of life
measure: Neurocognitive Assessments at Post-NICU Followup
timeFrame: up to 24 months of corrected gestational age
Locations:
city: Lexington
country: United States
facility: Kentucky Childrens Hospital Neonatal Intensive Care Unit
state: Kentucky
Study officials:
affiliation: UK Section of Neonatology
name: Vicki Whitehead, RN
role: STUDY_DIRECTOR
affiliation: UK Department of Pediatrics
name: John Bauer, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky Section of Neonatology
name: Hong Huang, MD-PhD
role: STUDY_DIRECTOR
References: