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

NICHD Neonatal Research Network

Status and phase: Terminated; Phase 3

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

Treatments: Drug: Dexamethasone; Procedure: Routine mechanical ventilation management; Drug: Placebo; Procedure: Minimal mechanical ventilation management

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00005777

NICHD-NRN-0018

U10HD021373 (U.S. NIH Grant/Contract)

U10HD021415 (U.S. NIH Grant/Contract)

M01RR000997 (U.S. NIH Grant/Contract)

U10HD027853 (U.S. NIH Grant/Contract)

U10HD034167 (U.S. NIH Grant/Contract)

M01RR000070 (U.S. NIH Grant/Contract)

M01RR006022 (U.S. NIH Grant/Contract)

U10HD027880 (U.S. NIH Grant/Contract)

U10HD027851 (U.S. NIH Grant/Contract)

U10HD027881 (U.S. NIH Grant/Contract)

M01RR000750 (U.S. NIH Grant/Contract)

U10HD021397 (U.S. NIH Grant/Contract)

M01RR001032 (U.S. NIH Grant/Contract)

M01RR008084 (U.S. NIH Grant/Contract)

U01HD036790 (U.S. NIH Grant/Contract)

U10HD034216 (U.S. NIH Grant/Contract)

U10HD021385 (U.S. NIH Grant/Contract)

U10HD027904 (U.S. NIH Grant/Contract)

U10HD027871 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

Chronic lung disease (CLD), also known as bronchopulmonary dysplasia (BPD), in very premature infants has been associated with mechanical ventilation and relative adrenal insufficiency.

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 trial was terminated by the Steering Committee when the interim analysis for the Data Safety and Monitoring Committee showed a higher rate of spontaneous gastrointestinal perforations in the dexamethasone-treated infants.

Neurodevelopment was assessed at 18-22 months postmenstrual age.

Enrollment: 220 patients

Sex: All

Ages: 5 minutes to 10 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Greater than 12 hrs of age and less than 10 days chronologic age
• 501-1000 gm
• Intubated and mechanically ventilated before 12 hrs
• Indwelling vascular catheter
• Infants 751-100 gm must be receiving FiO2 greater than 0.30 and have received at least 1 dose of surfactant at randomization
• Parental consent

Exclusion criteria

• Major congenital anomaly
• Symptomatic non-bacterial infection
• Permanent neuromuscular conditions that affect respiration
• Terminal illness (defined as pH values less than 6.8 for more than 2 hours or persistent bradycardia associated with hypoxia for more than 2 hours)
• Use of postnatal corticosteroids

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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220 participants in 4 patient groups

Minimal ventilation with Dexamethasone

Experimental group

Description:

Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy

Treatment:

Drug: Dexamethasone

Procedure: Minimal mechanical ventilation management

Minimal Ventilation without Dexamethasone

Experimental group

Description:

Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy

Treatment:

Drug: Placebo

Procedure: Minimal mechanical ventilation management

Routine ventilation with Dexamethasone

Active Comparator group

Treatment:

Drug: Dexamethasone

Procedure: Routine mechanical ventilation management

Routine ventilation without Dexamethasone

Active Comparator group

Treatment:

Drug: Placebo

Procedure: Routine mechanical ventilation management