Minimal Breathing Support and Early Steroids to Prevent Chronic Lung Disease in Extremely Premature Infants (SAVE)
- Conditions
- Bronchopulmonary DysplasiaRespiratory Distress SyndromeInfant, NewbornInfant, Low Birth WeightInfant, Small for Gestational AgeInfant, Premature
- Interventions
- Procedure: Minimal mechanical ventilation managementProcedure: Routine mechanical ventilation managementDrug: Placebo
- Registration Number
- NCT00005777
- Lead Sponsor
- NICHD Neonatal Research Network
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 220
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Minimal ventilation with Dexamethasone Minimal mechanical ventilation management Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy Minimal Ventilation without Dexamethasone Minimal mechanical ventilation management Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy Minimal Ventilation without Dexamethasone Placebo Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy Routine ventilation with Dexamethasone Routine mechanical ventilation management - Routine ventilation with Dexamethasone Dexamethasone - Routine ventilation without Dexamethasone Routine mechanical ventilation management - Routine ventilation without Dexamethasone Placebo - Minimal ventilation with Dexamethasone Dexamethasone Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy
- Primary Outcome Measures
Name Time Method Death or moderate to severe bronchopulmonary dysplasia 36 weeks postmenstrual age
- Secondary Outcome Measures
Name Time Method Death 18-22 months corrected age Mechanical ventilation 36 weeks postmenstrual age Pulmonary interstitial emphysema 36 weeks postmenstrual age Pneumothorax 36 weeks postmenstrual age Open-label steroids 36 weeks postmenstrual age Reintubation 36 weeks postmenstrual age Intracranial hemorrhage (IVH) III or IV 36 weeks postmenstrual age Periventricular leukomalacia 36 weeks postmenstrual age Necrotizing enterocolitis 36 weeks postmenstrual age Duration of oxygen supplementation 36 weeks postmenstrual age Duration of ventilation 36 weeks postmenstrual age Length of hospitalization Hospital discharge Death or neurodevelopmental impairment 18-22 months corrected age Neurodevelopmental impairment 18-22 months corrected age Cerebral palsy 18-22 months corrected age Bilateral blindness 18-22 months corrected age Deafness 18-22 months corrected age Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI) 18-22 months corrected age Rehospitalizations 18-22 months corrected age
Trial Locations
- Locations (13)
Stanford University
🇺🇸Palo Alto, California, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
University of Tennessee
🇺🇸Memphis, Tennessee, United States
RTI International
🇺🇸Durham, North Carolina, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Cincinnati Children's Medical Center
🇺🇸Cincinnati, Ohio, United States
Brown University, Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
University of Miami
🇺🇸Miami, Florida, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Yale University
🇺🇸New Haven, Connecticut, United States