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

Brain Injury Clinical Trial

Official title:

Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02221219
• Other study ID #: HD070792
• Secondary ID: R01HD070792
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2014
• Est. completion date: August 28, 2021

Study information

• Verified date: October 2021
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 256
• Est. completion date: August 28, 2021
• Est. primary completion date: October 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Weeks to 30 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injury
• Hemorrhage
• Intraventricular Hemorrhage
• Leukomalacia, Periventricular
• Periventricular Leukomalacia
• Renal Injury
• Wounds and Injuries

Intervention

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)

Locations

Country	Name	City	State
United States	Kentucky Childrens Hospital Neonatal Intensive Care Unit	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Hong Huang	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hematological Status	hematocrit, ferritin, hemoglobin at various times during NICU stay	first 60 days of life
Other	Inflammatory Stress	measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay	first 60 days of life
Other	Circulating Progenitor Cell Subpopulations	measures of several progenitor cell subtypes in blood during the NICU stay	first 60 days of life
Other	Neurocognitive Assessments at Post-NICU Followup	standardized neurocognitive assessments done at NICU graduate clinic.	up to 24 months of corrected gestational age
Primary	Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL	determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age	within first 60 days of life
Secondary	Number of Participants With Acute Kidney Injury	measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population).	first 60 days of life