Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
  Purpose

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.


Condition Intervention Phase
Bronchopulmonary Dysplasia
Respiratory Distress Syndrome
Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Procedure: Minimal mechanical ventilation management
Procedure: Routine mechanical ventilation management
Drug: Dexamethasone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Trial of Minimal Ventilator Support and Early Corticosteroid Therapy to Increase Survival Without Chronic Lung Disease in Extremely-Low-Birth-Weight Infants

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Death or moderate to severe bronchopulmonary dysplasia [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 220
Study Start Date: February 1998
Study Completion Date: September 2002
Primary Completion Date: September 1998 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Minimal ventilation with Dexamethasone
Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy
Procedure: Minimal mechanical ventilation management
Partial pressure of carbon dioxide (PCO2) target (>52 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.
Experimental: Minimal Ventilation without Dexamethasone
Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy
Procedure: Minimal mechanical ventilation management
Partial pressure of carbon dioxide (PCO2) target (>52 mm Hg)
Drug: Placebo
The infants in the placebo groups received equal volumes of saline.
Other Name: Saline
Active Comparator: Routine ventilation with Dexamethasone 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.
Active Comparator: Routine ventilation without Dexamethasone Procedure: Routine mechanical ventilation management
Partial pressure of carbon dioxide (PCO2) target <48 mm Hg)
Drug: Placebo
The infants in the placebo groups received equal volumes of saline.
Other Name: Saline

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.

  Eligibility

Ages Eligible for Study:   up to 10 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005777

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, North Carolina
RTI International
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Investigators
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
  More Information

Additional Information:
Publications:
Responsible Party: Waldemar A. Carlo, Lead Principal Investigator, University of Alabama - Birmingham
ClinicalTrials.gov Identifier: NCT00005777     History of Changes
Other Study ID Numbers: NICHD-NRN-0018, U10HD034216, U10HD034167, U10HD021397, U10HD027853, U10HD027871, U10HD021415, U10HD027904, U10HD027881, U10HD021385, U10HD027851, U10HD027880, U10HD021373, U01HD036790, M01RR008084, M01RR006022, M01RR000750, M01RR000997, M01RR000070, M01RR001032
Study First Received: June 1, 2000
Last Updated: January 9, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Prematurity
Chronic Lung Disease (CLD)
Dexamethasone
Glucocorticoids
Respiration, Artificial
Mechanical ventilation
Respiratory Insufficiency

Additional relevant MeSH terms:
Birth Weight
Bronchopulmonary Dysplasia
Lung Diseases
Respiratory Distress Syndrome, Newborn
Body Weight
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Injury
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Ventilator-Induced Lung Injury
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2014