Clinical trial NCT00005777: Minimal Breathing Support and Early Steroids to Prevent Chronic Lung Disease in Extremely Premature Infants (SAVE)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia
Respiratory Distress Syndrome
Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Keywords: NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Prematurity
Chronic Lung Disease (CLD)
Dexamethasone
Glucocorticoids
Respiration, Artificial
Mechanical ventilation
Respiratory Insufficiency
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2000-06-02
Enrollment: 220
Sex: ALL
Minimum age (years): 5
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Death or moderate to severe bronchopulmonary dysplasia
timeFrame: 36 weeks postmenstrual age
Secondary outcomes:
measure: Death
timeFrame: 36 weeks postmenstrual age
measure: Mechanical ventilation
timeFrame: 36 weeks postmenstrual age
measure: Pulmonary interstitial emphysema
timeFrame: 36 weeks postmenstrual age
measure: Pneumothorax
timeFrame: 36 weeks postmenstrual age
measure: Open-label steroids
timeFrame: 36 weeks postmenstrual age
measure: Reintubation
timeFrame: 36 weeks postmenstrual age
measure: Intracranial hemorrhage (IVH) III or IV
timeFrame: 36 weeks postmenstrual age
measure: Periventricular leukomalacia
timeFrame: 36 weeks postmenstrual age
measure: Necrotizing enterocolitis
timeFrame: 36 weeks postmenstrual age
measure: Duration of oxygen supplementation
timeFrame: 36 weeks postmenstrual age
measure: Duration of ventilation
timeFrame: 36 weeks postmenstrual age
measure: Length of hospitalization
timeFrame: Hospital discharge
measure: Death or neurodevelopmental impairment
timeFrame: 18-22 months corrected age
measure: Death
timeFrame: 18-22 months corrected age
measure: Neurodevelopmental impairment
timeFrame: 18-22 months corrected age
measure: Cerebral palsy
timeFrame: 18-22 months corrected age
measure: Bilateral blindness
timeFrame: 18-22 months corrected age
measure: Deafness
timeFrame: 18-22 months corrected age
measure: Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI)
timeFrame: 18-22 months corrected age
measure: Rehospitalizations
timeFrame: 18-22 months corrected age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
Study officials:
affiliation: University of Alabama at Birmingham
name: Waldemar A. Carlo, MD
role: STUDY_DIRECTOR
affiliation: Brigham and Women's Hospital
name: Ann R. Stark, MD
role: STUDY_DIRECTOR
affiliation: Brown University, Women & Infants Hospital
name: William Oh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University, Rainbow Babies & Children's Hospital
name: Avroy A. Fanaroff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Edward F. Donovan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Barbara J. Stoll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Charles R. Bauer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Lu-Ann Papile, MD
role: STUDY_DIRECTOR
affiliation: Stanford University
name: David K. Stevenson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Tennessee
name: Sheldon B. Korones, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Southwestern Medical Center
name: Jon E. Tyson, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Richard A. Ehrenkranz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: W. Kenneth Poole, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carlo WA, Stark AR, Wright LL, Tyson JE, Papile LA, Shankaran S, Donovan EF, Oh W, Bauer CR, Saha S, Poole WK, Stoll B. Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants. J Pediatr. 2002 Sep;141(3):370-4. doi: 10.1067/mpd.2002.127507.
citation: Stark AR, Carlo WA, Tyson JE, Papile LA, Wright LL, Shankaran S, Donovan EF, Oh W, Bauer CR, Saha S, Poole WK, Stoll BJ; National Institute of Child Health and Human Development Neonatal Research Network. Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 2001 Jan 11;344(2):95-101. doi: 10.1056/NEJM200101113440203.