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

NCT00005777 | Terminated Phase 3 DMC

• 20 other identifiers: NICHD-NRN-0018U10HD034216U10HD034167U10HD021397U10HD027853U10HD027871U10HD021415U10HD027904U10HD027881U10HD021385U10HD027851U10HD027880U10HD021373U01HD036790M01RR008084M01RR006022M01RR000750M01RR000997M01RR000070M01RR001032
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 13

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.

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

Outcome Measures

Primary Outcomes (1)

• Death or moderate to severe bronchopulmonary dysplasia

  36 weeks postmenstrual age

Secondary Outcomes (20)

• Death

  36 weeks postmenstrual age

• Mechanical ventilation

  36 weeks postmenstrual age

• Pulmonary interstitial emphysema

  36 weeks postmenstrual age

• Pneumothorax

  36 weeks postmenstrual age

• Open-label steroids

  36 weeks postmenstrual age

Study Arms (4)

Minimal ventilation with Dexamethasone

EXPERIMENTAL

Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy

Procedure: Minimal mechanical ventilation management; Drug: Dexamethasone

Minimal Ventilation without Dexamethasone

EXPERIMENTAL

Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy

Procedure: Minimal mechanical ventilation management; Drug: Placebo

Routine ventilation with Dexamethasone

ACTIVE COMPARATOR

Procedure: Routine mechanical ventilation management; Drug: Dexamethasone

Routine ventilation without Dexamethasone

ACTIVE COMPARATOR

Procedure: Routine mechanical ventilation management; Drug: Placebo

Interventions

Minimal mechanical ventilation management PROCEDURE

Partial pressure of carbon dioxide (PCO2) target (\>52 mm Hg)

Minimal Ventilation without Dexamethasone; Minimal ventilation with Dexamethasone

Routine mechanical ventilation management PROCEDURE

Partial pressure of carbon dioxide (PCO2) target \<48 mm Hg)

Routine ventilation with Dexamethasone; Routine ventilation without Dexamethasone

Dexamethasone DRUG

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.

Minimal ventilation with Dexamethasone; Routine ventilation with Dexamethasone

Placebo DRUG

The infants in the placebo groups received equal volumes of saline.

Also known as: Saline

Minimal Ventilation without Dexamethasone; Routine ventilation without Dexamethasone

Eligibility Criteria

• Age: 5 Minutes - 10 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Greater than 12 hrs of age and less than 10 days chronologic age
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (13)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Tennessee

Memphis, Tennessee, 38163, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

Related 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. doi: 10.1067/mpd.2002.127507.

  PMID: 12219057 RESULT

• 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.

  PMID: 11150359 RESULT

Related Links

• NICHD Neonatal Research Network

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Respiratory Distress Syndrome; Premature Birth; Respiratory Aspiration; Respiratory Insufficiency

Interventions

Dexamethasone; Sodium Chloride

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiration Disorders; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Waldemar A. Carlo, MD

  University of Alabama at Birmingham

  STUDY DIRECTOR

• Ann R. Stark, MD

  Brigham and Women's Hospital

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

• Lu-Ann Papile, MD

  University of New Mexico

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: June 1, 2000
• First Posted: June 2, 2000
• Study Start: February 1, 1998
• Primary Completion: September 1, 1998
• Study Completion: September 1, 2002
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

US (13)