Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury
Condition: Intraventricular Hemorrhage; Periventricular Leukomalacia; Brain Injury; Renal Injury
MeSH terms: Brain Injuries; Leukomalacia, Periventricular; Hemorrhage; Wounds and Injuries
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Indomethacin; delay in umbilical cord clamp at birth; placebo infusion; immediate cord clamp at birth
Intervention type(s): Drug; Procedure; Drug; Procedure
Intervention description(s): indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants; provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note); saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff); no delay in umbilical cord clamp; <10sec (recorded in delivery note)
Other intervention name(s): indocin
Intervention MeSH terms: Indomethacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: infant; brain injury; renal; indomethacin