Clinical trial NCT03019367: Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2
Official title: Premature Infants Receiving Milking or Delayed Cord Clamping: Randomized Controlled Multicenter Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intraventricular Haemorrhage Neonatal
Death; Neonatal
Keywords: Premature infants
Umbilical cord milking
Delayed cord clamping
Intraventricular Hemorrhage
Death
Lead sponsor: Sharp HealthCare
Sponsor class: OTHER
Collaborators: name: Sharp Mary Birch Hospital for Women & Newborns
name: Loma Linda University
name: University of Pittsburgh
name: Providence Hospital
name: University of Alabama at Birmingham
name: University of Alberta
name: University College Cork
name: University of Ulm
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Christiana Care Health Services
name: Sharp Grossmont Hospital
name: University of Utah
name: University of Mississippi Medical Center
name: PIH Health Good Samaritan Hospital
name: University of California, Irvine
name: Children's Hospital Medical Center, Cincinnati
name: Cook County Health
name: St. Louis University
name: LAC+USC Medical Center
First posted: 2017-01-12
Enrollment: 1201
Sex: ALL
Minimum age (years): 23
Maximum age (years): 33
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of severe IVH or death
timeFrame: Through study completion at death or discharge, up to 6 months corrected gestational age (CGA)
Secondary outcomes:
measure: All Grade IVH
timeFrame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
measure: Severe IVH (Grade 3 or 4)
timeFrame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
measure: Hemoglobin/Hematocrit at 4 hours
timeFrame: 4 +/- 2 hours of life
measure: Incidence of Severe IVH or death in infants <28 weeks gestation
timeFrame: Through study completion at discharge, up to 6 months corrected gestational age (CGA)
measure: Delivery room interventions
timeFrame: In the first 10 minutes of life
measure: Blood pressures in the first 24 hours of life
timeFrame: In the first 24 hours of life
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda Medical Center
state: California
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
city: Los Angeles
country: United States
facility: PIH Health Good Samaritan Hospital
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Grossmont Hospital
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women and Newborns
state: California
city: Newark
country: United States
facility: Christiana Care
state: Delaware
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Edmonton
country: Canada
facility: Governors of University of Alberta
state: Alberta
city: Ulm
country: Germany
facility: University of ULM
state: Baden-Wurttemberg
city: Cork
country: Ireland
facility: Cork University Maternity Hospital
Study officials:
affiliation: Sharp HealthCare
name: Anup C Katheria, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.