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

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.

Conditions

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

Interventions

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)

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Hong Huang

  lead OTHER

Principal Investigators

• Vicki Whitehead, RN · UK Section of Neonatology

• John Bauer, PhD · UK Department of Pediatrics

• Hong Huang, MD-PhD · University of Kentucky Section of Neonatology

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

24 Weeks

Max Age

30 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-08-31

Primary Completion

2019-10-27

Completion

2021-08-28

FDA Drug

Yes

Countries

• United States

Study Locations