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

This study has been terminated.
(The trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy.)
Sponsor:
Collaborator:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00005777
First received: June 1, 2000
Last updated: January 9, 2011
Last verified: September 2010

June 1, 2000
January 9, 2011
February 1998
September 1998   (final data collection date for primary outcome measure)
Death or moderate to severe bronchopulmonary dysplasia [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00005777 on ClinicalTrials.gov Archive Site
  • Death [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Mechanical ventilation [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Pulmonary interstitial emphysema [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Pneumothorax [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Open-label steroids [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Reintubation [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Intracranial hemorrhage (IVH) III or IV [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Periventricular leukomalacia [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Necrotizing enterocolitis [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Duration of oxygen supplementation [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Duration of ventilation [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Length of hospitalization [ Time Frame: Hospital discharge ] [ Designated as safety issue: Yes ]
  • Death or neurodevelopmental impairment [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Neurodevelopmental impairment [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Cerebral palsy [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Bilateral blindness [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Deafness [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI) [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Rehospitalizations [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Minimal Breathing Support and Early Steroids to Prevent Chronic Lung Disease in Extremely Premature Infants (SAVE)
Randomized Trial of Minimal Ventilator Support and Early Corticosteroid Therapy to Increase Survival Without Chronic Lung Disease in Extremely-Low-Birth-Weight Infants

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Bronchopulmonary Dysplasia
  • Respiratory Distress Syndrome
  • Infant, Newborn
  • Infant, Low Birth Weight
  • Infant, Small for Gestational Age
  • Infant, Premature
  • 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.
    Other Name: Saline
  • Experimental: Minimal ventilation with Dexamethasone
    Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy
    Interventions:
    • Procedure: Minimal mechanical ventilation management
    • Drug: Dexamethasone
  • Experimental: Minimal Ventilation without Dexamethasone
    Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy
    Interventions:
    • Procedure: Minimal mechanical ventilation management
    • Drug: Placebo
  • Active Comparator: Routine ventilation with Dexamethasone
    Interventions:
    • Procedure: Routine mechanical ventilation management
    • Drug: Dexamethasone
  • Active Comparator: Routine ventilation without Dexamethasone
    Interventions:
    • Procedure: Routine mechanical ventilation management
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
220
September 2002
September 1998   (final data collection date for primary outcome measure)

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
Both
up to 10 Days
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00005777
NICHD-NRN-0018, U10HD034216, U10HD034167, U10HD021397, U10HD027853, U10HD027871, U10HD021415, U10HD027904, U10HD027881, U10HD021385, U10HD027851, U10HD027880, U10HD021373, U01HD036790, M01RR008084, M01RR006022, M01RR000750, M01RR000997, M01RR000070, M01RR001032
Yes
Waldemar A. Carlo, Lead Principal Investigator, University of Alabama - Birmingham
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
Study Director: Waldemar A. Carlo, MD University of Alabama at Birmingham
Study Director: Ann R. Stark, MD Brigham and Women's Hospital
Principal Investigator: William Oh, MD Brown University, Women & Infants Hospital
Principal Investigator: Avroy A. Fanaroff, MD Case Western Reserve University, Rainbow Babies & Children's Hospital
Principal Investigator: Edward F. Donovan, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Charles R. Bauer, MD University of Miami
Study Director: Lu-Ann Papile, MD University of New Mexico
Principal Investigator: David K. Stevenson, MD Stanford University
Principal Investigator: Sheldon B. Korones, MD University of Tennessee
Principal Investigator: Jon E. Tyson, MD MPH University of Texas Southwestern Medical Center
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: W. Kenneth Poole, PhD RTI International
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
September 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP