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Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2 (PREMOD2)

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ClinicalTrials.gov Identifier: NCT03019367
Recruitment Status : Recruiting
First Posted : January 12, 2017
Last Update Posted : February 28, 2020
Sponsor:
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
Information provided by (Responsible Party):
Anup Katheria, M.D., Sharp HealthCare

Tracking Information
First Submitted Date  ICMJE November 21, 2016
First Posted Date  ICMJE January 12, 2017
Last Update Posted Date February 28, 2020
Actual Study Start Date  ICMJE June 6, 2017
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 2, 2019)
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
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
Incidence of severe IVH or death [ Time Frame: Through study completion at death or discharge, up to 6 months corrected gestational age (CGA) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2018)
  • All Grade IVH [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 4 +/- 2 hours of life ]
    hemoglobin/hematocrit
  • 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) ]
    Severe intraventricular hemorrhage (grade 3 or 4) in infants born under 28 weeks gestational age
  • Delivery room interventions [ Time Frame: 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 [ Time Frame: In the first 24 hours of life ]
    Blood pressure on admission, 6, 12, 18 and 24 hours of life
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
  • Incidence of death or neurodevelopmental impairment at 22-26 months corrected gestational age [ Time Frame: Through follow up completion at 26 months corrected gestational age ]
  • All Grade Intraventricular Hemorrhage [ 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) ]
  • Cerebral StO2 during Resuscitation [ Time Frame: In the first 10 minutes of life ]
  • Cerebral StO2 in the NICU [ Time Frame: In the first 72 hours of life ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2
Official Title  ICMJE Premature Infants Receiving Milking or Delayed Cord Clamping: Randomized Controlled Multicenter Non-inferiority Trial
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 consequently 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Prevention
Condition  ICMJE
  • Intraventricular Haemorrhage Neonatal
  • Death; Neonatal
Intervention  ICMJE
  • Procedure: Umbilical cord milking UCM
    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.
  • Procedure: Delayed cord clamping DCC
    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 Arms  ICMJE
  • Active Comparator: Umbilical cord milking UCM
    Milking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds.
    Intervention: Procedure: Umbilical cord milking UCM
  • Active Comparator: Delayed cord clamping DCC
    Delayed clamping of the umbilical cord for at least 60 seconds.
    Intervention: Procedure: Delayed cord clamping DCC
Publications * Katheria A, Reister F, Essers J, Mendler M, Hummler H, Subramaniam A, Carlo W, Tita A, Truong G, Davis-Nelson S, Schmölzer 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 28, 2018)
1200
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2017)
1500
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 23 to 32 +6 Gestational age (currently enrolling 29 to 32+6 weeks)
  • Multiples unless monochorionic

Exclusion Criteria:

  • Congenital anomalies
  • Major cardiac defects
  • Placental abruption or previa with hemorrhage
  • Cord prolapse
  • Hydrops
  • Bleeding Accreta
  • Monochorionic multiples (i.e. Di/Mo or Mo/Mo twins)
  • Fetal or maternal risk (i.e. compromise)
  • Parents declined study
  • Unlikely to return for 2 yr Follow Up
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 23 Weeks to 33 Weeks   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anup C Katheria, MD 858 939-4170 anup.katheria@sharp.com
Contact: Kathy M Arnell, RN 858 939-4966 kathy.arnell@sharp.com
Listed Location Countries  ICMJE Canada,   Germany,   Ireland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03019367
Other Study ID Numbers  ICMJE PREMOD2
1R01HD088646-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data will be made available per NICHD requirements (National Institute of Child Health and Human Development).
Supporting Materials: Statistical Analysis Plan (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.
Responsible Party Anup Katheria, M.D., Sharp HealthCare
Study Sponsor  ICMJE Sharp HealthCare
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Principal Investigator: Anup C Katheria, MD Sharp HealthCare
PRS Account Sharp HealthCare
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP