Clinical Trial: Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH

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 Summary: 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 (n=400 total cases).
Sponsor: John Bauer

Current Primary Outcome: fraction of survivors with no severe IVH (grades 3 or 4) or PVL [ Time Frame: within first 60 days of life ]

determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age


Original Primary Outcome: Same as current

Current Secondary Outcome: occurrence of renal injury and/or dysfunction [ Time Frame: first 60 days of life ]

measures of BUN, Creatinine, and cystatin C at various times during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population)


Original Secondary Outcome: Same as current

Information By: University of Kentucky

Dates:
Date Received: August 18, 2014
Date Started: August 2014
Date Completion: December 2020
Last Updated: April 17, 2017
Last Verified: April 2017