Trial Outcomes & Findings for Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury (NCT NCT02221219)
NCT ID: NCT02221219
Last Updated: 2021-11-23
Results Overview
determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
256 participants
Primary outcome timeframe
within first 60 days of life
Results posted on
2021-11-23
Participant Flow
Participant milestones
| Measure |
Immediate Cord Clamp & Placebo IV Solution
This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Delay Cord Clamp & Placebo IV Solution
A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
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)
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
|
Immediate Cord Clamp & Indomethacin IV
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Indomethacin iv & Delayed Cord Clamp
A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
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)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
36
|
87
|
41
|
92
|
|
Overall Study
COMPLETED
|
36
|
87
|
41
|
92
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury
Baseline characteristics by cohort
| Measure |
Immediate Cord Clamp & Placebo IV Solution
n=36 Participants
This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Delay Cord Clamp & Placebo IV Solution
n=87 Participants
A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
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)
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
|
Immediate Cord Clamp & Indomethacin IV
n=41 Participants
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Indomethacin iv & Delayed Cord Clamp
n=92 Participants
A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
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)
|
Total
n=256 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
26.2 weeks
STANDARD_DEVIATION 1.8 • n=5 Participants
|
26.6 weeks
STANDARD_DEVIATION 2.0 • n=7 Participants
|
26.6 weeks
STANDARD_DEVIATION 1.8 • n=5 Participants
|
26.4 weeks
STANDARD_DEVIATION 1.8 • n=4 Participants
|
26.5 weeks
STANDARD_DEVIATION 1.9 • n=21 Participants
|
|
Sex/Gender, Customized
Male
|
19 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
47 Participants
n=4 Participants
|
132 Participants
n=21 Participants
|
|
Sex/Gender, Customized
Female
|
17 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
122 Participants
n=21 Participants
|
|
Sex/Gender, Customized
Unknown
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
90 Participants
n=4 Participants
|
245 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
76 Participants
n=4 Participants
|
213 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
36 participants
n=5 Participants
|
87 participants
n=7 Participants
|
41 participants
n=5 Participants
|
92 participants
n=4 Participants
|
256 participants
n=21 Participants
|
|
Birth Weight
|
797.2 grams
STANDARD_DEVIATION 267.4 • n=5 Participants
|
935.1 grams
STANDARD_DEVIATION 295.0 • n=7 Participants
|
902.4 grams
STANDARD_DEVIATION 369.8 • n=5 Participants
|
916.8 grams
STANDARD_DEVIATION 254.8 • n=4 Participants
|
903.9 grams
STANDARD_DEVIATION 291.2 • n=21 Participants
|
PRIMARY outcome
Timeframe: within first 60 days of lifedetermined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age
Outcome measures
| Measure |
Immediate Cord Clamp & Placebo IV Solution
n=36 Participants
This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Delay Cord Clamp & Placebo IV Solution
n=87 Participants
A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
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)
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
|
Immediate Cord Clamp & Indomethacin IV
n=41 Participants
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Indomethacin iv & Delayed Cord Clamp
n=92 Participants
A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
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)
|
|---|---|---|---|---|
|
Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL
|
22.2 percent of participants
|
14.9 percent of participants
|
17.1 percent of participants
|
10.9 percent of participants
|
SECONDARY outcome
Timeframe: first 60 days of lifemeasures 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).
Outcome measures
| Measure |
Immediate Cord Clamp & Placebo IV Solution
n=36 Participants
This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Delay Cord Clamp & Placebo IV Solution
n=87 Participants
A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
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)
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
|
Immediate Cord Clamp & Indomethacin IV
n=41 Participants
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Indomethacin iv & Delayed Cord Clamp
n=92 Participants
A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
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)
|
|---|---|---|---|---|
|
Number of Participants With Acute Kidney Injury
No acute kidney injury
|
20 participants
|
48 participants
|
23 participants
|
48 participants
|
|
Number of Participants With Acute Kidney Injury
Grade 1 Acute Kidney Injury
|
8 participants
|
27 participants
|
15 participants
|
29 participants
|
|
Number of Participants With Acute Kidney Injury
Grade 2 Acute Kidney Injury
|
6 participants
|
8 participants
|
3 participants
|
14 participants
|
|
Number of Participants With Acute Kidney Injury
Grade 3 Acute Kidney Injury
|
2 participants
|
4 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Acute Kidney Injury
Grade 4 Acute Kidney Injury
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: first 60 days of lifehematocrit, ferritin, hemoglobin at various times during NICU stay
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: first 60 days of lifemeasurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: first 60 days of lifemeasures of several progenitor cell subtypes in blood during the NICU stay
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 24 months of corrected gestational agestandardized neurocognitive assessments done at NICU graduate clinic.
Outcome measures
Outcome data not reported
Adverse Events
Immediate Cord Clamp & Placebo IV Solution
Serious events: 5 serious events
Other events: 0 other events
Deaths: 6 deaths
Delay Cord Clamp & Placebo IV Solution
Serious events: 7 serious events
Other events: 0 other events
Deaths: 10 deaths
Immediate Cord Clamp & Indomethacin IV
Serious events: 3 serious events
Other events: 0 other events
Deaths: 2 deaths
Indomethacin iv & Delayed Cord Clamp
Serious events: 10 serious events
Other events: 0 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
Immediate Cord Clamp & Placebo IV Solution
n=36 participants at risk
This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Delay Cord Clamp & Placebo IV Solution
n=87 participants at risk
A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
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)
placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
|
Immediate Cord Clamp & Indomethacin IV
n=41 participants at risk
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
immediate cord clamp at birth: no delay in umbilical cord clamp; \<10sec (recorded in delivery note)
|
Indomethacin iv & Delayed Cord Clamp
n=92 participants at risk
A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
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)
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Necrotizing Enterocolitis
|
2.8%
1/36 • Number of events 1 • First 60 days of life.
|
0.00%
0/87 • First 60 days of life.
|
0.00%
0/41 • First 60 days of life.
|
0.00%
0/92 • First 60 days of life.
|
|
Pregnancy, puerperium and perinatal conditions
Extreme Prematurity
|
11.1%
4/36 • Number of events 4 • First 60 days of life.
|
5.7%
5/87 • Number of events 5 • First 60 days of life.
|
2.4%
1/41 • Number of events 1 • First 60 days of life.
|
5.4%
5/92 • Number of events 5 • First 60 days of life.
|
|
Respiratory, thoracic and mediastinal disorders
Free Air in Abdomen
|
2.8%
1/36 • Number of events 2 • First 60 days of life.
|
0.00%
0/87 • First 60 days of life.
|
0.00%
0/41 • First 60 days of life.
|
1.1%
1/92 • Number of events 1 • First 60 days of life.
|
|
Blood and lymphatic system disorders
Septic Shock
|
0.00%
0/36 • First 60 days of life.
|
1.1%
1/87 • Number of events 1 • First 60 days of life.
|
0.00%
0/41 • First 60 days of life.
|
0.00%
0/92 • First 60 days of life.
|
|
Gastrointestinal disorders
Bowel Perforation
|
0.00%
0/36 • First 60 days of life.
|
1.1%
1/87 • Number of events 1 • First 60 days of life.
|
2.4%
1/41 • Number of events 1 • First 60 days of life.
|
3.3%
3/92 • Number of events 3 • First 60 days of life.
|
|
Infections and infestations
CMV
|
0.00%
0/36 • First 60 days of life.
|
1.1%
1/87 • Number of events 1 • First 60 days of life.
|
0.00%
0/41 • First 60 days of life.
|
0.00%
0/92 • First 60 days of life.
|
|
General disorders
Multiorgan Failure
|
0.00%
0/36 • First 60 days of life.
|
1.1%
1/87 • Number of events 1 • First 60 days of life.
|
0.00%
0/41 • First 60 days of life.
|
0.00%
0/92 • First 60 days of life.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/36 • First 60 days of life.
|
0.00%
0/87 • First 60 days of life.
|
2.4%
1/41 • Number of events 1 • First 60 days of life.
|
1.1%
1/92 • Number of events 1 • First 60 days of life.
|
Other adverse events
Adverse event data not reported
Additional Information
Research Protocol Manager/Clinical/UKHC
University of Kentucky
Phone: (859) 257-1000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place