Minimal Breathing Support and Early Steroids to Prevent Chronic Lung Disease in Extremely Premature Infants (SAVE)

Summary

This multicenter clinical trial tested whether minimal ventilation decreases death or BPD. Infants with birth weight 501g to 1000g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide \[PCO(2)\] target \>52 mm Hg) or routine ventilation (PCO(2) target \<48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. Blood gases, ventilator settings, and FiO2 were recorded for 10 days; complications and outcomes were monitored to discharge. The infants' neurodevelopment was evaluated at 18-22 months corrected age.

Conditions

• Bronchopulmonary Dysplasia
• Respiratory Distress Syndrome
• Infant, Newborn
• Infant, Low Birth Weight
• Infant, Small for Gestational Age
• Infant, Premature

Interventions

PROCEDURE

Minimal mechanical ventilation management

Partial pressure of carbon dioxide (PCO2) target (\>52 mm Hg)

PROCEDURE

Routine mechanical ventilation management

Partial pressure of carbon dioxide (PCO2) target \<48 mm Hg)

DRUG

Dexamethasone

Treatment with the study medication was initiated within 24 hours after birth. The dexamethasone-treated infants received a 10-day tapered course (0.15 mg of dexamethasone per kilogram per day for three days, followed by 0.10 mg per kilogram for three days, 0.05 mg per kilogram for two days, and 0.02 mg per kilogram for two days), with the daily dose divided in half and given at 12-hour intervals intravenously or orally, if an intravenous catheter was no longer in place.

DRUG

Placebo

The infants in the placebo groups received equal volumes of saline.

Sponsors & Collaborators

• National Center for Research Resources (NCRR)

  collaborator NIH

• NICHD Neonatal Research Network

  lead NETWORK

Principal Investigators

• Waldemar A. Carlo, MD · University of Alabama at Birmingham

• Ann R. Stark, MD · Brigham and Women's Hospital

• William Oh, MD · Brown University, Women & Infants Hospital

• Avroy A. Fanaroff, MD · Case Western Reserve University, Rainbow Babies & Children's Hospital

• Edward F. Donovan, MD · Children's Hospital Medical Center, Cincinnati

• Barbara J. Stoll, MD · Emory University

• Charles R. Bauer, MD · University of Miami

• Lu-Ann Papile, MD · University of New Mexico

• David K. Stevenson, MD · Stanford University

• Sheldon B. Korones, MD · University of Tennessee

• Jon E. Tyson, MD MPH · University of Texas Southwestern Medical Center

• Seetha Shankaran, MD · Wayne State University

• Richard A. Ehrenkranz, MD · Yale University

• W. Kenneth Poole, PhD · RTI International

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

5 Minutes

Max Age

10 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1998-02-28

Primary Completion

1998-09-30

Completion

2002-09-30

Countries

• United States

Study Locations