Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2

Study Overview
=================
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.

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

Conditions
-----------------
Intraventricular Haemorrhage Neonatal, Death; Neonatal

Intervention / Treatment
-----------------
* Procedure: Umbilical cord milking UCM
* Procedure: Delayed cord clamping DCC


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 23 Weeks
Maximum Age: 33 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Umbilical cord milking UCM<br>Milking the umbilical cord 4 times towards the infant at a speed of 20cm/2seconds. | Procedure: Umbilical cord milking UCM<br>* 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.<br>|
| Active Comparator: Delayed cord clamping DCC<br>Delayed clamping of the umbilical cord for at least 60 seconds. | Procedure: Delayed cord clamping DCC<br>* At delivery, delayed cord clamping will be performed by having the delivering obstetrician delay clamping of the umbilical cord for at least 60 seconds.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Grade IVH | Any intraventricular hemorrhage (grades 1-4) | 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) | Through study completion at discharge, up to 6 months corrected gestational age (CGA) | 
| Hemoglobin/Hematocrit at 4 hours | hemoglobin/hematocrit | 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 | 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 | 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 | In the first 24 hours of life | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Death, Premature infants, Umbilical cord milking, Delayed cord clamping, Intraventricular Hemorrhage