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

Bronchopulmonary Dysplasia Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00005777
• Other study ID #: NICHD-NRN-0018
• Secondary ID: U10HD034216U10HD
• Status: Terminated
• Phase: Phase 3
• First received: June 1, 2000
• Last updated: June 3, 2015
• Start date: February 1998
• Est. completion date: September 2002

Study information

• Verified date: June 2015
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 220
• Est. completion date: September 2002
• Est. primary completion date: September 1998
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 10 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Birth Weight
• Bronchopulmonary Dysplasia
• Infant, Low Birth Weight
• Infant, Newborn
• Infant, Premature
• Infant, Small for Gestational Age
• Lung Diseases
• Premature Birth
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Procedure:
• Minimal mechanical ventilation management
Partial pressure of carbon dioxide (PCO2) target (>52 mm Hg)
• 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.
• Placebo
The infants in the placebo groups received equal volumes of saline.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	RTI International	Durham	North Carolina
United States	University of Tennessee	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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 in extremel — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death or moderate to severe bronchopulmonary dysplasia		36 weeks postmenstrual age	Yes
Secondary	Death		36 weeks postmenstrual age	Yes
Secondary	Mechanical ventilation		36 weeks postmenstrual age	Yes
Secondary	Pulmonary interstitial emphysema		36 weeks postmenstrual age	Yes
Secondary	Pneumothorax		36 weeks postmenstrual age	Yes
Secondary	Open-label steroids		36 weeks postmenstrual age	Yes
Secondary	Reintubation		36 weeks postmenstrual age	Yes
Secondary	Intracranial hemorrhage (IVH) III or IV		36 weeks postmenstrual age	Yes
Secondary	Periventricular leukomalacia		36 weeks postmenstrual age	Yes
Secondary	Necrotizing enterocolitis		36 weeks postmenstrual age	Yes
Secondary	Duration of oxygen supplementation		36 weeks postmenstrual age	Yes
Secondary	Duration of ventilation		36 weeks postmenstrual age	Yes
Secondary	Length of hospitalization		Hospital discharge	Yes
Secondary	Death or neurodevelopmental impairment		18-22 months corrected age	Yes
Secondary	Death		18-22 months corrected age	Yes
Secondary	Neurodevelopmental impairment		18-22 months corrected age	Yes
Secondary	Cerebral palsy		18-22 months corrected age	Yes
Secondary	Bilateral blindness		18-22 months corrected age	Yes
Secondary	Deafness		18-22 months corrected age	Yes
Secondary	Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI)		18-22 months corrected age	Yes
Secondary	Rehospitalizations		18-22 months corrected age	Yes

External Links

•   Cochrane meta-analysis: "Postnatal corticosteroids in preterm infants with chronic lung disease: late treatment (> 3 weeks)."
•   NICHD Neonatal Research Network