Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2

NCT03019367 | Completed DMC

• 2 other identifiers: PREMOD21R01HD088646-01A1
• Study Type: interventional
• Target: 1,201
• Locations: 4 countries
• Sites: 18

Brief 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.

Conditions

Intraventricular Haemorrhage Neonatal; Death; Neonatal

Keywords

Premature infants; Umbilical cord milking; Delayed cord clamping; Intraventricular Hemorrhage; Death

Outcome Measures

Primary Outcomes (1)

• Incidence of severe IVH or death

  Severe intraventricular hemorrhage of grade 3 or 4 or death

  Through study completion at death or discharge, up to 6 months corrected gestational age (CGA)

Secondary Outcomes (6)

• All Grade IVH

  Through study completion at discharge, up to 6 months corrected gestational age (CGA)

• Severe IVH (Grade 3 or 4)

  Through study completion at discharge, up to 6 months corrected gestational age (CGA)

• Hemoglobin/Hematocrit at 4 hours

  4 +/- 2 hours of life

• Incidence of Severe IVH or death in infants <28 weeks gestation

  Through study completion at discharge, up to 6 months corrected gestational age (CGA)

• Delivery room interventions

  In the first 10 minutes of life

Study Arms (2)

Umbilical cord milking UCM

ACTIVE COMPARATOR

Milking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds.

Procedure: Umbilical cord milking UCM

Delayed cord clamping DCC

ACTIVE COMPARATOR

Delayed clamping of the umbilical cord for at least 60 seconds.

Procedure: Delayed cord clamping DCC

Interventions

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.

Umbilical cord milking UCM

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.

Delayed cord clamping DCC

Eligibility Criteria

• Age: 23 Weeks - 33 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sharp HealthCare: lead
• Sharp Mary Birch Hospital for Women & Newborns: collaborator
• Loma Linda University: collaborator
• University of Pittsburgh: collaborator
• Providence Hospital: collaborator
• University of Alabama at Birmingham: collaborator
• University of Alberta: collaborator
• University College Cork: collaborator
• University of Ulm: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Christiana Care Health Services: collaborator
• Sharp Grossmont Hospital: collaborator
• University of Utah: collaborator
• University of Mississippi Medical Center: collaborator
• PIH Health Good Samaritan Hospital: collaborator
• University of California, Irvine: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• Cook County Health: collaborator
• St. Louis University: collaborator
• LAC+USC Medical Center: collaborator

Study Sites (18)

University of Alabama

Birmingham, Alabama, 35294-0004, United States

Location

Loma Linda Medical Center

Loma Linda, California, 92350, United States

Location

LAC+USC Medical Center

Los Angeles, California, 90033, United States

Location

PIH Health Good Samaritan Hospital

Los Angeles, California, 90033, United States

Location

University of California, Irvine Medical Center

Orange, California, 92868, United States

Location

Sharp Grossmont Hospital

San Diego, California, 91942, United States

Location

Sharp Mary Birch Hospital for Women and Newborns

San Diego, California, 92123, United States

Location

Christiana Care

Newark, Delaware, 19718, United States

Location

John H. Stroger, Jr. Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Providence St. Vincent Medical Center

Portland, Oregon, 97225-6603, United States

Location

Magee-Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Governors of University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

University of ULM

Ulm, Baden-Wurttemberg, 89075, Germany

Location

Cork University Maternity Hospital

Cork, Ireland

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

Related Links

• Website for trial
• NIRS Sub-study PREMOD2
• Followup Study-PREMOD2

MeSH Terms

Conditions

Perinatal Death; Premature Birth; Death

Interventions

Umbilical Cord Clamping

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications

Intervention Hierarchy (Ancestors)

Delivery, Obstetric; Obstetric Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Anup C Katheria, MD

  Sharp HealthCare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: It is not possible to blind the delivering obstetrician, however all other caregivers will be blinded. The procedure will be documented as "placental transfusion" in the delivery summary or admission-progress notes and all study assessments whether primary (head US) or secondary (neurodevelopmental exams) will be performed by blinded team members.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neonatal Research Institute

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: January 12, 2017
• Study Start: June 6, 2017
• Primary Completion: September 16, 2022
• Study Completion: September 16, 2022
• Last Updated: November 23, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: 2 years after primary publication
• Access Criteria: An archived dataset with documentation will be made available for additional uses by outside investigators, in collaboration with the study investigators. We will work with NICHD program staff to develop a broad data sharing plan over time.

Locations

DE (1); IE (1); CA (1); US (15)