Intraventricular Haemorrhage NeonatalPREMOD2NCT03019367
Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2
A study testing Umbilical cord milking UCM and Delayed cord clamping DCC in people with Intraventricular Haemorrhage Neonatal and Death; Neonatal, run by Sharp HealthCare at 18 sites in 4 countries.
Trial summary
This study is being done to find out whether umbilical cord milking (UCM) is at least as good as or better than delayed cord clamping (DCC) to reduce bleeding in the brain or prevent death in premature newborns. Read more about this study
- Who is it for?
- Ages 23 to 33 weeks
- Conditions the study is for
- Intraventricular Haemorrhage Neonatal, Death; Neonatal
- What is being tested?
- Umbilical cord milking UCM and Delayed cord clamping DCC
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,201 participants
- Where
- 18 sitesin 4 countries
- Study dates
- 6 Jun 2017to 16 Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 23 to 33 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 23 to 32 +6 Gestational age (currently enrolling 29 to 32+6 weeks)
- Multiples without Twin-to-twin Transfusion Syndrome (TTTS)
Who cannot join
- Congenital anomalies
- Major cardiac defects
- Placental abruption or previa with hemorrhage
- Cord prolapse
- Hydrops
- Bleeding Accreta
Show all 10Show fewer
- Monochorionic multiples with evidence of TTTS
- Fetal or maternal risk (i.e. compromise)
- Parents declined study
- Unlikely to return for 2 yr Follow Up
Trial locations and contacts
18 sites in 4 countries.
18 sites in 4 countries
United States15 sites
University of Alabama
Birmingham, Alabama, 35294-0004
John H. Stroger, Jr. Hospital of Cook County
Chicago, Illinois, 60612
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Loma Linda Medical Center
Loma Linda, California, 92350
LAC+USC Medical Center
Los Angeles, California, 90033
PIH Health Good Samaritan Hospital
Los Angeles, California, 90033
Christiana Care
Newark, Delaware, 19718
University of California, Irvine Medical Center
Orange, California, 92868
Magee-Womens Hospital
Pittsburgh, Pennsylvania, 15213
Providence St. Vincent Medical Center
Portland, Oregon, 97225-6603
University of Utah
Salt Lake City, Utah, 84112
Sharp Grossmont Hospital
San Diego, California, 91942
Sharp Mary Birch Hospital for Women and Newborns
San Diego, California, 92123
St. Louis University
St Louis, Missouri, 63104
About this study
Official title: Premature Infants Receiving Milking or Delayed Cord Clamping: Randomized Controlled Multicenter Non-inferiority Trial
This study is being done to find out whether umbilical cord milking (UCM) is at least as good as or better than delayed cord clamping (DCC) to reduce bleeding in the brain or prevent death in premature newborns. The investigators will study short and long term outcomes of infants delivered before 32 weeks gestation that receive either UCM or DCC.
- The trial was stopped by the DSMB for safety in the small strata. They subsequently allowed for continuation of the trial in infants 29-32+6 wk GA.
Read the detailed description
Aim 1. Compare the incidence of severe intraventricular hemorrhage (IVH) and/or death in premature newborns <33 weeks gestational age (GA) delivered by C/S receiving UCM to those receiving DCC.
Hypothesis1: First demonstrate infants in the UCM group are not inferior to the DCC group (reject H10).
Hypothesis2: If H1 is true, demonstrate lower incidence of severe IVH and/or death in UCM infants compared to DCC.
Aim 2. Compare the safety and efficacy profiles of premature newborns <33 weeks GA delivered by C/S receiving UCM vs. DCC during their hospitalization.
Hypothesis3: UCM group will have a decreased need for resuscitation interventions with no differences in bilirubin or polycythemia compared to DCC.
Hypothesis4: UCM group will have improved blood pressures in the first 24 hours of life compared to DCC.
Aim 3 (exploratory). To compare the outcomes of premature newborns <33 weeks GA delivered by C/S (Cesarean section) (from Aims 1 and 2) with those born by V/D (vaginal delivery) receiving UCM or DCC.
- Being tested
- Umbilical cord milking UCM, Delayed cord clamping DCC
- Keywords
- Premature infants, Umbilical cord milking, Delayed cord clamping, Intraventricular Hemorrhage, Death
- Medical subject headings
- Perinatal Death, Premature Birth, Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Umbilical cord milking UCMProcedure or surgery
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before it is clamped. This procedure infuses a placental transfusion of blood into the preterm neonate and can be done in 15-20 seconds.
Delayed cord clamping DCCProcedure or surgery
At delivery, delayed cord clamping will be performed by having the delivering obstetrician delay clamping of the umbilical cord for at least 60 seconds.
| Study group | Role | What they receive |
|---|---|---|
| Umbilical cord milking UCM | Active comparator | Milking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds. Receives: Procedure: Umbilical cord milking UCM |
| Delayed cord clamping DCC | Active comparator | Delayed clamping of the umbilical cord for at least 60 seconds. Receives: Procedure: Delayed cord clamping DCC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of severe IVH or death
Severe intraventricular hemorrhage of grade 3 or 4 or death
Measured: Through study completion at death or discharge, up to 6 months corrected gestational age (CGA)
Secondary outcomes (6)
All Grade IVH
Any intraventricular hemorrhage (grades 1-4)
Measured: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
Severe IVH (Grade 3 or 4)
Severe intraventricular hemorrhage (bleeding in the brain parenchyma and/or ventricular dilation)
Measured: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
Hemoglobin/Hematocrit at 4 hours
hemoglobin/hematocrit
Measured: 4 +/- 2 hours of life
Incidence of Severe IVH or death in infants <28 weeks gestation
Severe intraventricular hemorrhage (grade 3 or 4) in infants born under 28 weeks gestational age
Measured: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
Delivery room interventions
Resuscitation interventions including positive pressure ventilation, continuous positive airway pressure, intubation, chest compressions and medications
Measured: In the first 10 minutes of life
Blood pressures in the first 24 hours of life
Blood pressure on admission, 6, 12, 18 and 24 hours of life
Measured: In the first 24 hours of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2017 (estimated)
- Study start6 Jun 2017
- Primary completion16 Sep 2022
- Study completion16 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intraventricular Haemorrhage NeonatalStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,201 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sharp HealthCare
- Sponsor type
- University, hospital or other
- Collaborators
- Sharp Mary Birch Hospital for Women & Newborns, Loma Linda University, University of Pittsburgh, Providence Hospital, University of Alabama at Birmingham, University of Alberta, University College Cork, University of Ulm, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Christiana Care Health Services, Sharp Grossmont Hospital, University of Utah, University of Mississippi Medical Center, PIH Health Good Samaritan Hospital, University of California, Irvine, Children's Hospital Medical Center, Cincinnati, Cook County Health, St. Louis University, LAC+USC Medical Center
- Responsible party
- Principal investigator, Anup Katheria, M.D., Sharp HealthCare
- Investigators
- Anup C Katheria, MD, Principal investigator, Sharp HealthCare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03019367
- Sponsor's protocol ID
- PREMOD2
- Other IDs
- 1R01HD088646-01A1
- Acronym
- PREMOD2
- Status last verified
- Nov 2022
- First submitted
- 21 Nov 2016
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be made available per NICHD requirements (National Institute of Child Health and Human Development).
Publications
Katheria AC, Allman P, Szychowski JM, Essers J, Carlo WA, Schmolzer GM, Dempsey E, Yanowitz T, Kaempf J, Vora F, Bhat S, Arnell K, Rich W, Varner M. Perinatal Outcomes of Subjects Enrolled in a Multicenter Trial with a Waiver of Antenatal Consent. Am J Perinatol. 2022 Jun;39(8):904-908. doi: 10.1055/s-0040-1719184. Epub 2020 Nov 3.
PubMed 33142340Katheria A, Reister F, Essers J, Mendler M, Hummler H, Subramaniam A, Carlo W, Tita A, Truong G, Davis-Nelson S, Schmolzer G, Chari R, Kaempf J, Tomlinson M, Yanowitz T, Beck S, Simhan H, Dempsey E, O'Donoghue K, Bhat S, Hoffman M, Faksh A, Arnell K, Rich W, Finer N, Vaucher Y, Khanna P, Meyers M, Varner M, Allman P, Szychowski J, Cutter G. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA. 2019 Nov 19;322(19):1877-1886. doi: 10.1001/jama.2019.16004.
PubMed 31742630
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Premature Infants Receiving Milking or Delayed Cord Clamping: Randomized Controlled Multicenter Non-inferiority Trial
- ClinicalTrials.gov ID
- NCT03019367
- Acronym / sponsor ID
- PREMOD2 / PREMOD2
- Keywords
- Premature infants, Umbilical cord milking, Delayed cord clamping, Intraventricular Hemorrhage, Death
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,201 participants (actual)
- Lead sponsor
- Sharp HealthCareUniversity, hospital or other
- Collaborators
- Sharp Mary Birch Hospital for Women & Newborns, Loma Linda University, University of Pittsburgh, Providence Hospital, University of Alabama at Birmingham, University of Alberta, University College Cork, University of Ulm, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Christiana Care Health Services, Sharp Grossmont Hospital, University of Utah, University of Mississippi Medical Center, PIH Health Good Samaritan Hospital, University of California, Irvine, Children's Hospital Medical Center, Cincinnati, Cook County Health, St. Louis University, LAC+USC Medical Center
- Study start
- 6 Jun 2017 (actual)
- Primary completion
- 16 Sep 2022 (actual)
- Study completion
- 16 Sep 2022 (actual)
- First posted
- 12 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to find out whether umbilical cord milking (UCM) is at least as good as or better than delayed cord clamping (DCC) to reduce bleeding in the brain or prevent death in premature newborns. The investigators will study short and long term outcomes of infants delivered before 32 weeks gestation that receive either UCM or DCC.
- The trial was stopped by the DSMB for safety in the small strata. They subsequently allowed for continuation of the trial in infants 29-32+6 wk GA.
Detailed description
Aim 1. Compare the incidence of severe intraventricular hemorrhage (IVH) and/or death in premature newborns <33 weeks gestational age (GA) delivered by C/S receiving UCM to those receiving DCC.
Hypothesis1: First demonstrate infants in the UCM group are not inferior to the DCC group (reject H10).
Hypothesis2: If H1 is true, demonstrate lower incidence of severe IVH and/or death in UCM infants compared to DCC.
Aim 2. Compare the safety and efficacy profiles of premature newborns <33 weeks GA delivered by C/S receiving UCM vs. DCC during their hospitalization.
Hypothesis3: UCM group will have a decreased need for resuscitation interventions with no differences in bilirubin or polycythemia compared to DCC.
Hypothesis4: UCM group will have improved blood pressures in the first 24 hours of life compared to DCC.
Aim 3 (exploratory). To compare the outcomes of premature newborns <33 weeks GA delivered by C/S (Cesarean section) (from Aims 1 and 2) with those born by V/D (vaginal delivery) receiving UCM or DCC.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Umbilical cord milking UCM | Active comparator | Procedure: Umbilical cord milking UCMMilking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds. |
| Delayed cord clamping DCC | Active comparator | Procedure: Delayed cord clamping DCCDelayed clamping of the umbilical cord for at least 60 seconds. |
Who may qualify
- Ages
- 23 to 33 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 23 to 32 +6 Gestational age (currently enrolling 29 to 32+6 weeks)
- Multiples without Twin-to-twin Transfusion Syndrome (TTTS)
Key exclusion criteria (10 listed)
- Congenital anomalies
- Major cardiac defects
- Placental abruption or previa with hemorrhage
- Cord prolapse
- Hydrops
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 |
|---|---|---|
| Umbilical cord milking UCMAt delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before it is clamped. This procedure infuses a placental transfusion of blood into the preterm neonate and can be done in 15-20 seconds. | Procedure or surgery | Umbilical cord milking UCM |
| Delayed cord clamping DCCAt delivery, delayed cord clamping will be performed by having the delivering obstetrician delay clamping of the umbilical cord for at least 60 seconds. | Procedure or surgery | Delayed cord clamping DCC |
Primary outcome
Incidence of severe IVH or death
Time frame: Through study completion at death or discharge, up to 6 months corrected gestational age (CGA)
Severe intraventricular hemorrhage of grade 3 or 4 or death
6 secondary outcomes
All Grade IVH
Time frame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
Severe IVH (Grade 3 or 4)
Time frame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
Hemoglobin/Hematocrit at 4 hours
Time frame: 4 +/- 2 hours of life
Incidence of Severe IVH or death in infants <28 weeks gestation
Time frame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
Delivery room interventions
Time frame: In the first 10 minutes of life
Blood pressures in the first 24 hours of life
Time frame: In the first 24 hours of life
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2022.
- Derived from this study: PubMed 33142340Katheria AC, Allman P, Szychowski JM, Essers J, Carlo WA, Schmolzer GM, Dempsey E, Yanowitz T, Kaempf J, Vora F, Bhat S, Arnell K, Rich W, Varner M. Perinatal Outcomes of Subjects Enrolled in a Multicenter Trial with a Waiver of Antenatal Consent. Am J Perinatol. 2022 Jun;39(8):904-908. doi: 10.1055/s-0040-1719184. Epub 2020 Nov 3.
- Derived from this study: PubMed 31742630Katheria A, Reister F, Essers J, Mendler M, Hummler H, Subramaniam A, Carlo W, Tita A, Truong G, Davis-Nelson S, Schmolzer G, Chari R, Kaempf J, Tomlinson M, Yanowitz T, Beck S, Simhan H, Dempsey E, O'Donoghue K, Bhat S, Hoffman M, Faksh A, Arnell K, Rich W, Finer N, Vaucher Y, Khanna P, Meyers M, Varner M, Allman P, Szychowski J, Cutter G. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA. 2019 Nov 19;322(19):1877-1886. doi: 10.1001/jama.2019.16004.
- NIRS Sub-study PREMOD2Link provided by the sponsor.
- Followup Study-PREMOD2Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data will be made available per NICHD requirements (National Institute of Child Health and Human Development).
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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.
Anup C Katheria, MD principal investigator
Sharp HealthCare
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Umbilical cord milking UCM and Delayed cord clamping DCC in people with Intraventricular Haemorrhage Neonatal and Death; Neonatal, run by Sharp HealthCare at 18 sites in 4 countries.
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 10 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 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Canada, Germany, Ireland. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of severe IVH or death (time frame: Through study completion at death or discharge, up to 6 months corrected gestational age (CGA)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03019367, which also lists 2 linked publications.
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 2022.