Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2

NCT03019367 — Not applicable, Completed, 1201 participants, Sharp HealthCare

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

Premature Infants Receiving Milking or Delayed Cord Clamping: Randomized Controlled Multicenter Non-inferiority Trial

Registry	NCT03019367, acronym PREMOD2
Status	Completed
Phase	Not applicable
Study type	Interventional; randomized, parallel, masking: triple, prevention
Enrollment	1201 (Actual)
Sponsor	Sharp HealthCare (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
Conditions	Intraventricular Haemorrhage Neonatal, Death; Neonatal
Interventions	Umbilical cord milking UCM, Delayed cord clamping DCC (Procedure)
Dates	start 2017-06-06, primary completion 2022-09-16, completion 2022-09-16, first posted 2017-01-12, last updated 2022-11-23
Locations	18 sites in United States, Canada, Germany, Ireland

-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. 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.

Expand all sections · Collapse all

+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.

+Arms and interventions

Arm	Type	Interventions	Description
Umbilical cord milking UCM	Active comparator	Procedure: Umbilical cord milking UCM	Milking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds.
Delayed cord clamping DCC	Active comparator	Procedure: Delayed cord clamping DCC	Delayed clamping of the umbilical cord for at least 60 seconds.

Umbilical cord milking UCM (Procedure): 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 DCC (Procedure): At delivery, delayed cord clamping will be performed by having the delivering obstetrician delay clamping of the umbilical cord for at least 60 seconds.

+Outcome measures

Primary outcomes

Incidence of severe IVH or death [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

Secondary outcomes

All Grade IVH [Through study completion at discharge, up to 6 months corrected gestational age (CGA)]: Any intraventricular hemorrhage (grades 1-4)
Severe IVH (Grade 3 or 4) [Through study completion at discharge, up to 6 months corrected gestational age (CGA)]: Severe intraventricular hemorrhage (bleeding in the brain parenchyma and/or ventricular dilation)
Hemoglobin/Hematocrit at 4 hours [4 +/- 2 hours of life]: hemoglobin/hematocrit
Incidence of Severe IVH or death in infants <28 weeks gestation [Through study completion at discharge, up to 6 months corrected gestational age (CGA)]: Severe intraventricular hemorrhage (grade 3 or 4) in infants born under 28 weeks gestational age
Delivery room interventions [In the first 10 minutes of life]: Resuscitation interventions including positive pressure ventilation, continuous positive airway pressure, intubation, chest compressions and medications
Blood pressures in the first 24 hours of life [In the first 24 hours of life]: Blood pressure on admission, 6, 12, 18 and 24 hours of life

+Eligibility

Sex: All, ages: 23 Weeks to 33 Weeks

Inclusion Criteria:

* 23 to 32 +6 Gestational age (currently enrolling 29 to 32+6 weeks)
* Multiples without Twin-to-twin Transfusion Syndrome (TTTS)

Exclusion Criteria:

* Congenital anomalies
* Major cardiac defects
* Placental abruption or previa with hemorrhage
* Cord prolapse
* Hydrops
* Bleeding Accreta
* Monochorionic multiples with evidence of TTTS
* Fetal or maternal risk (i.e. compromise)
* Parents declined study
* Unlikely to return for 2 yr Follow Up

+Locations (18)

Facility	City	Country
University of Alabama	Birmingham, Alabama	United States
Loma Linda Medical Center	Loma Linda, California	United States
LAC+USC Medical Center	Los Angeles, California	United States
PIH Health Good Samaritan Hospital	Los Angeles, California	United States
University of California, Irvine Medical Center	Orange, California	United States
Sharp Grossmont Hospital	San Diego, California	United States
Sharp Mary Birch Hospital for Women and Newborns	San Diego, California	United States
Christiana Care	Newark, Delaware	United States
John H. Stroger, Jr. Hospital of Cook County	Chicago, Illinois	United States
University of Mississippi Medical Center	Jackson, Mississippi	United States
St. Louis University	St Louis, Missouri	United States
Cincinnati Children's Hospital	Cincinnati, Ohio	United States
Providence St. Vincent Medical Center	Portland, Oregon	United States
Magee-Womens Hospital	Pittsburgh, Pennsylvania	United States
University of Utah	Salt Lake City, Utah	United States
Governors of University of Alberta	Edmonton, Alberta	Canada
University of ULM	Ulm, Baden-Wurttemberg	Germany
Cork University Maternity Hospital	Cork	Ireland

+Publications

Results publication: 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. PMID 33142340
Results publication: Katheria 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. PMID 31742630

+Investigators

Anup C Katheria, MD, Principal investigator, Sharp HealthCare

+Funding

NIH grants: R01HD088646