VentFirst: A Multicenter RCT of Assisted Ventilation During Delayed Cord Clamping for Extremely Preterm Infants

The purpose of this study is to determine whether providing ventilatory assistance prior to umbilical cord clamping influences the occurrence of intraventricular hemorrhage (IVH) in extremely preterm (EPT) infants, compared to standard care of providing ventilatory assistance after cord clamping.

Study Overview

• Status: Active, not recruiting
• Conditions: Intraventricular Hemorrhage
• Intervention / Treatment: Procedure: Standard 30-60 Seconds Cord Clamping; Procedure: VentFirst 120 Seconds Cord Clamping

Detailed Description

Newborns with gestational age 23 wks 0 days through 28 wks 6 days are randomized to control (delayed cord clamping for at least 30 seconds, or up to 60 seconds if breathing spontaneously, with ventilatory assistance provided after) or the VentFirst intervention (ventilatory assistance with continuous positive airway pressure or positive pressure ventilation given starting 30 seconds after birth and cord clamping at 120 seconds).

The primary outcome is lack of IVH on 7-10 day head ultrasound or death before day 7.

The study was designed to test the impact of the intervention in each of two cohorts:

1. Infants not breathing well 30 seconds after birth
2. Infants breathing well 30 seconds after birth

Randomization and analysis is stratified by gestational age category:

1. 23 0/6 to 25 6/7 weeks' gestation
2. 26 0/7 to 28 6/7 weeks' gestation

• Study Type: Interventional
• Enrollment (Actual): 570
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gina Duda; Phone Number: (434) 924-9553; Email: GMS4X@uvahealth.org
• Study Contact Backup: Name: Justin Alicea; Phone Number: (434) 243-5350; Email: XZY7TW@uvahealth.org

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary
    • Edmonton, Alberta, Canada, T5H 3V9
      • University of Alberta, Edmonton
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis
  • Colorado
    • Denver, Colorado, United States, 80045-2571
      • University of Colorado
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • University of Indiana
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-6110
      • Brigham & Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63103-2006
      • St. Louis University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Oregon
    • Portland, Oregon, United States, 37239-0000
      • Oregon Health & Science University
  • Virginia
    • Charlottesville, Virginia, United States, 22904-4195
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 23 0/7 - 28 6/7 weeks' gestation at delivery

Exclusion Criteria:

• Life-threatening condition of fetus (e.g. severe hydrops, lethal chromosomal abnormality, severe congenital malformation)
• Suspected severe fetal anemia
• Monochorionic or monoamniotic twins
• Multiple gestation greater than twins
• Decision made for comfort care only
• Medical emergency necessitating emergency delivery (e.g. complete placental abruption)
• Obstetrician or Neonatology concern for inappropriateness of the study intervention based on maternal or fetal factors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard 30-60 Seconds Cord Clamping; Standard treatment for extremely preterm infants which is delayed cord clamping 30-60 seconds after birth, and assisted ventilation after cord clamping.	Procedure: Standard 30-60 Seconds Cord Clamping; The infant is stimulated to breathe after birth. If the infant is not breathing well, the cord is clamped at 30 seconds. If the baby is breathing well, the cord is clamped at 60 seconds. Ventilatory assistance is given after cord clamping.
Experimental: VentFirst 120 Seconds Cord Clamping; Assisted ventilation (face mask continuous positive airway pressure, CPAP, or positive pressure ventilation, PPV) is provided prior to cord clamping at 120 seconds.	Procedure: VentFirst 120 Seconds Cord Clamping; The infant is stimulated to breathe after birth. If the infant is not breathing well, PPV by face mask is given starting at 30 seconds. If the baby is breathing well, CPAP is given starting at 30 seconds. The cord is clamped at 120 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraventricular Hemorrhage on Head Ultrasound or death before 7 days of age	presence of any grade IVH on HUS	7-10 days after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5 minute Apgar Score <5	Low Apgar score (<5) at 5 minutes	5 minutes after birth
Lowest hematocrit in first 24 hours	Median, 25th & 75th percentiles	First 24 hours after birth
Medication for low blood pressure in first 24 hours	Hydrocortisone and/or vasopressor for hypotension	First 24 hours after birth
Number of red blood cell transfusions birth through day 10	Median, 25th & 75th percentiles	First 10 days after birth
Severe brain injury on head ultrasound	Grade 3-4 IVH and/or cerebellar hemorrhage and/or cystic periventricular leukomalacia on head ultrasound at 7-10 days of age and/or near 36 weeks' postmenstrual age	Birth through 36 weeks' postmenstrual age
Death	All-cause mortality	Birth through 36 weeks' postmenstrual age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal post-partum hemorrhage	>= 1000 mL estimated blood loss	First 24 hours after delivery
Maternal red blood cell transfusion	Administration of an RBC transfusion	Prior to maternal hospital discharge
Maternal retained placenta	Retained placenta	Prior to hospital discharge
Maternal post-partum delivery related infection	Diagnosis of a delivery related infection	Prior to maternal hospital discharge
Apgar scores	Apgar scores taken in the delivery room (1, 5, 10 minutes)	1 minute, 5 minutes, and 10 minutes after delivery
Umbilical Cord Blood Gas	Umbilical cord venous and arterial pH	In delivery room
Chest compressions or epinephrine	occurrence of infant chest compressions or administration of epinephrine	In delivery room
Volume Bolus	administration of a volume bolus	In delivery room
Intubation	Endotracheal intubation	In delivery room
Admission hypothermia <36.5°C	<36.5°C	at admission to the Neonatal Intensive Care Unit
Pneumothorax	Diagnosis of pneumothorax requiring intervention	first 24 hours after delivery
NICU admission temperature	Infant's NICU admission temperature	At NICU admission
SNAPPE-II Score	Score for Neonatal Acute Physiology-Perinatal Extension	First 12 hours after birth
Red blood cell transfusion	Administration of an RBC transfusion	First 24 hours after birth
Highest hematocrit	Infant's highest hematocrit (before transfusion)	First 24 hours after birth
Lowest mean arterial blood pressure	Infant's lowest mean arterial blood pressure (cuff or arterial catheter)	First 24 hours after birth
Volume Bolus	Any volume bolus including the delivery room, and including NICU packed red blood cells, platelets, plasma, saline, or other fluid bolus	First 24 hours after birth
Surfactant administration	Administration of surfactant	First 10 days after birth
Mechanical ventilation days	Number of days on mechanical ventilation via an endotracheal tube	First 10 days after birth
Early-Onset Septicemia	Positive blood culture in first 3 days and treated with at least 5 days of antibiotics	<72 hours after birth
Highest bilirubin	Highest bilirubin recorded	First 10 days after birth
Phototherapy duration	Number of days on phototherapy	First 10 days after birth
Intraventricular hemorrhage	Highest grade of IVH	Prior to 36 weeks' postmenstrual age
Cerebellar hemorrhage	occurrence of cerebellar hemorrhage	Prior to 36 weeks' postmenstrual age
Late-Onset Septicemia	Positive blood culture after first 3 days and treated with at least 5 days of antibiotics	Prior to 36 weeks' postmenstrual age
Cystic Periventricular Leukomalacia (cPVL)	Occurrence of cPVL	Prior to 36 weeks' postmenstrual age
Patent Ductus Arteriosus (PDA)	occurrence of PDA requiring pharmacological or surgical treatment	Prior to 36 weeks' postmenstrual age
Spontaneous intestinal perforation (SIP)	SIP without NEC and requiring surgery or peritoneal drain	Prior to 36 weeks' postmenstrual age
Necrotizing Enterocolitis (NEC)	Occurrence of NEC modified Bell's stage 2-3	Prior to 36 weeks' postmenstrual age
Bronchopulmonary Dysplasia (BPD)	Occurrence of BPD receiving continuous supplemental oxygen	At 36 weeks' postmenstrual age
Severe ROP	occurrence of ROP stage 3 or treated with laser or bevacizumab	Prior to 36 weeks' postmenstrual age

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: University of Colorado, Denver; Mayo Clinic; University of Alabama at Birmingham; Columbia University; Brigham and Women's Hospital; University of Alberta; University of California, Davis; Oregon Health and Science University; University of Calgary; Indiana University; St. Louis University
• Investigators: Principal Investigator: Karen Fairchild, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): March 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimated): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Intraventricular Hemorrhage; Umbilical Cord Clamping; Extremely Preterm Infants
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: 18783

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO