Intraventricular HemorrhagePhase 1/2NCT02221219
Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury
A Phase 1/2 study testing Indomethacin, delay in umbilical cord clamp at birth and immediate cord clamp at birth in people with Intraventricular Hemorrhage and Periventricular Leukomalacia, run by Hong Huang at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 24 to 30 weeks
- Conditions the study is for
- Intraventricular Hemorrhage, Periventricular Leukomalacia, Brain Injury
- What is being tested?
- Indomethacin, delay in umbilical cord clamp at birth and immediate cord clamp at birth
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 256 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to 28 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 30 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- pregnant women admitted >24weeks and <30weeks gestational age,
- in-hospital birth (allowing for cord clamp randomization)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Kentucky Childrens Hospital Neonatal Intensive Care Unit
Lexington, Kentucky, 40506
About this study
Official title: Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH
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.
Read the 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.
- Being tested
- Indomethacin, delay in umbilical cord clamp at birth, placebo infusion, immediate cord clamp at birth
- Keywords
- infant, brain injury, renal, indomethacin
- Medical subject headings
- Leukomalacia, Periventricular, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IndomethacinDrug
Also called indocin
indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants
delay in umbilical cord clamp at birthProcedure or surgery
provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)
placebo infusionDrug
saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
immediate cord clamp at birthProcedure or surgery
no delay in umbilical cord clamp; <10sec (recorded in delivery note)
| Study group | Role | What they receive |
|---|---|---|
| immediate cord clamp & placebo IV solution | Placebo comparator | 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. Receives: Drug: placebo infusion; Procedure: immediate cord clamp at birth |
| delay cord clamp & placebo IV solution | Experimental | 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. Receives: Procedure: delay in umbilical cord clamp at birth; Drug: placebo infusion |
| immediate cord clamp & indomethacin IV | Active comparator | 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). Receives: Drug: Indomethacin; Procedure: immediate cord clamp at birth |
| indomethacin iv & delayed cord clamp | Experimental | 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. Receives: Drug: Indomethacin; Procedure: delay in umbilical cord clamp at birth |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: within first 60 days of life
Secondary outcomes (1)
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).
Measured: first 60 days of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2014 (estimated)
- Study startAug 2014
- Primary completion27 Oct 2019
- Study completion28 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Intraventricular HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 256 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hong Huang
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Hong Huang, University of Kentucky
- Investigators
- Vicki Whitehead, RN, Study director, UK Section of NeonatologyJohn Bauer, PhD, Principal investigator, UK Department of PediatricsHong Huang, MD-PhD, Study director, University of Kentucky Section of Neonatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02221219
- Sponsor's protocol ID
- HD070792
- Other IDs
- R01HD070792
- Status last verified
- Oct 2021
- First submitted
- 18 Aug 2014
- Last updated
- 23 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH
- ClinicalTrials.gov ID
- NCT02221219
- Acronym / sponsor ID
- HD070792
- Keywords
- infant, brain injury, renal, indomethacin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 256 participants (actual)
- Lead sponsor
- Hong HuangUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Aug 2014 (actual)
- Primary completion
- 27 Oct 2019 (actual)
- Study completion
- 28 Aug 2021 (actual)
- First posted
- 20 Aug 2014 (estimated)
- Results
- Posted 8 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| immediate cord clamp & placebo IV solution | Placebo comparator | Drug: placebo infusion, Procedure: immediate cord clamp at birthThis 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. |
| delay cord clamp & placebo IV solution | Experimental | Procedure: delay in umbilical cord clamp at birth, Drug: placebo infusionA delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. |
| immediate cord clamp & indomethacin IV | Active comparator | Drug: Indomethacin, Procedure: immediate cord clamp at birthUmbilical 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 iv & delayed cord clamp | Experimental | Drug: Indomethacin, Procedure: delay in umbilical cord clamp at birthA 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. |
Who may qualify
- Ages
- 24 to 30 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- pregnant women admitted >24weeks and <30weeks gestational age,
- in-hospital birth (allowing for cord clamp randomization)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IndomethacinAlso: indocinindomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants | Drug | immediate cord clamp & indomethacin IV, indomethacin iv & delayed cord clamp |
| delay in umbilical cord clamp at birthprovision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) | Procedure or surgery | delay cord clamp & placebo IV solution, indomethacin iv & delayed cord clamp |
| placebo infusionsaline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) | Drug | delay cord clamp & placebo IV solution, immediate cord clamp & placebo IV solution |
| immediate cord clamp at birthno delay in umbilical cord clamp; <10sec (recorded in delivery note) | Procedure or surgery | immediate cord clamp & indomethacin IV, immediate cord clamp & placebo IV solution |
Primary outcome
Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL
Time frame: within first 60 days of life
determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age
1 secondary outcome
Number of Participants With Acute Kidney Injury
Time frame: first 60 days of life
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Intraventricular Hemorrhage
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Enrolling by invitationObservational study
Intelligent Physiological Monitoring to Predict Preterm Brain Injury
Cerebral Palsy (CP), Intraventricular Hemorrhage Neonatal
Active, not recruiting
Delayed Cord Clamping With Oxygen In Extremely Low Gestation Infants
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Active, not recruiting
aSAH Treatment Based on Intraventricular ICP Monitoring: A Prospective, Multicenter, Randomized and Controlled Trial
Aneurysmal Subarachnoid Hemorrhage, Intacranial Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vicki Whitehead, RN study director
UK Section of Neonatology
John Bauer, PhD principal investigator
UK Department of Pediatrics
Hong Huang, MD-PhD study director
University of Kentucky Section of Neonatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Indomethacin, delay in umbilical cord clamp at birth and immediate cord clamp at birth in people with Intraventricular Hemorrhage and Periventricular Leukomalacia, run by Hong Huang at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL (time frame: within first 60 days of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2021.