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

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ClinicalTrials.gov Identifier: NCT00005777
Recruitment Status : Terminated (The trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy.)
First Posted : June 2, 2000
Last Update Posted : June 8, 2015
Sponsor:
Collaborator:
National Center for Research Resources (NCRR)
Information provided by:
NICHD Neonatal Research Network

Tracking Information
First Submitted Date  ICMJE June 1, 2000
First Posted Date  ICMJE June 2, 2000
Last Update Posted Date June 8, 2015
Study Start Date  ICMJE February 1998
Actual Primary Completion Date September 1998   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2011)
Death or moderate to severe bronchopulmonary dysplasia [ Time Frame: 36 weeks postmenstrual age ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2011)
  • Death [ Time Frame: 36 weeks postmenstrual age ]
  • Mechanical ventilation [ Time Frame: 36 weeks postmenstrual age ]
  • Pulmonary interstitial emphysema [ Time Frame: 36 weeks postmenstrual age ]
  • Pneumothorax [ Time Frame: 36 weeks postmenstrual age ]
  • Open-label steroids [ Time Frame: 36 weeks postmenstrual age ]
  • Reintubation [ Time Frame: 36 weeks postmenstrual age ]
  • Intracranial hemorrhage (IVH) III or IV [ Time Frame: 36 weeks postmenstrual age ]
  • Periventricular leukomalacia [ Time Frame: 36 weeks postmenstrual age ]
  • Necrotizing enterocolitis [ Time Frame: 36 weeks postmenstrual age ]
  • Duration of oxygen supplementation [ Time Frame: 36 weeks postmenstrual age ]
  • Duration of ventilation [ Time Frame: 36 weeks postmenstrual age ]
  • Length of hospitalization [ Time Frame: Hospital discharge ]
  • Death or neurodevelopmental impairment [ Time Frame: 18-22 months corrected age ]
  • Death [ Time Frame: 18-22 months corrected age ]
  • Neurodevelopmental impairment [ Time Frame: 18-22 months corrected age ]
  • Cerebral palsy [ Time Frame: 18-22 months corrected age ]
  • Bilateral blindness [ Time Frame: 18-22 months corrected age ]
  • Deafness [ Time Frame: 18-22 months corrected age ]
  • Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI) [ Time Frame: 18-22 months corrected age ]
  • Rehospitalizations [ Time Frame: 18-22 months corrected age ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Minimal Breathing Support and Early Steroids to Prevent Chronic Lung Disease in Extremely Premature Infants (SAVE)
Official Title  ICMJE Randomized Trial of Minimal Ventilator Support and Early Corticosteroid Therapy to Increase Survival Without Chronic Lung Disease in Extremely-Low-Birth-Weight Infants
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Bronchopulmonary Dysplasia
  • Respiratory Distress Syndrome
  • Infant, Newborn
  • Infant, Low Birth Weight
  • Infant, Small for Gestational Age
  • Infant, Premature
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 9, 2011)
220
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE September 2002
Actual Primary Completion Date September 1998   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 10 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00005777
Other Study ID Numbers  ICMJE NICHD-NRN-0018
U10HD034216 ( U.S. NIH Grant/Contract )
U10HD034167 ( U.S. NIH Grant/Contract )
U10HD021397 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
U10HD021415 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD027881 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U01HD036790 ( U.S. NIH Grant/Contract )
M01RR008084 ( U.S. NIH Grant/Contract )
M01RR006022 ( U.S. NIH Grant/Contract )
M01RR000750 ( U.S. NIH Grant/Contract )
M01RR000997 ( U.S. NIH Grant/Contract )
M01RR000070 ( U.S. NIH Grant/Contract )
M01RR001032 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Waldemar A. Carlo, Lead Principal Investigator, University of Alabama - Birmingham
Study Sponsor  ICMJE NICHD Neonatal Research Network
Collaborators  ICMJE National Center for Research Resources (NCRR)
Investigators  ICMJE
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
PRS Account NICHD Neonatal Research Network
Verification Date June 2015

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