NCT02221219

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

Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 256 (actual)
• Sponsor: Hong Huang · Academic / Other
• Sex: All
• Age: 24 Weeks – 30 Weeks
• Healthy volunteers: Not accepted

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.

Conditions

• Intraventricular Hemorrhage
• Periventricular Leukomalacia
• Brain Injury
• Renal Injury

Interventions

Type	Name	Description
DRUG	Indomethacin	indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
PROCEDURE	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)
DRUG	placebo infusion	saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
PROCEDURE	immediate cord clamp at birth	no delay in umbilical cord clamp; \<10sec (recorded in delivery note)

Timeline

• Start date: 2014-08-01
• Primary completion: 2019-10-27
• Completion: 2021-08-28
• First posted: 2014-08-20
• Last updated: 2021-11-23
• Results posted: 2020-12-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study