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

NCT ID: NCT00005777

Last Updated: 2015-06-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-02-28

Study Completion Date

2002-09-30

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Minimal ventilation with Dexamethasone

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

Group Type EXPERIMENTAL

Minimal mechanical ventilation management

Intervention Type PROCEDURE

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

Dexamethasone

Intervention Type 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 without Dexamethasone

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

Group Type EXPERIMENTAL

Minimal mechanical ventilation management

Intervention Type PROCEDURE

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

Placebo

Intervention Type DRUG

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

Routine ventilation with Dexamethasone

Group Type ACTIVE_COMPARATOR

Routine mechanical ventilation management

Intervention Type PROCEDURE

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

Dexamethasone

Intervention Type 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.

Routine ventilation without Dexamethasone

Group Type ACTIVE_COMPARATOR

Routine mechanical ventilation management

Intervention Type PROCEDURE

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

Placebo

Intervention Type DRUG

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

Interventions

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Minimal mechanical ventilation management

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

Intervention Type PROCEDURE

Routine mechanical ventilation management

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

Intervention Type PROCEDURE

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.

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Saline

Eligibility Criteria

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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
Minimum Eligible Age

5 Minutes

Maximum Eligible Age

10 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Center for Research Resources (NCRR)

NIH

Sponsor Role collaborator

NICHD Neonatal Research Network

NETWORK

Sponsor Role lead

Responsible Party

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University of Alabama - Birmingham

Principal Investigators

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Waldemar A. Carlo, MD

Role: STUDY_DIRECTOR

University of Alabama at Birmingham

Ann R. Stark, MD

Role: STUDY_DIRECTOR

Brigham and Women's Hospital

William Oh, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University, Women & Infants Hospital

Avroy A. Fanaroff, MD

Role: PRINCIPAL_INVESTIGATOR

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

Edward F. Donovan, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Barbara J. Stoll, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Charles R. Bauer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Lu-Ann Papile, MD

Role: STUDY_DIRECTOR

University of New Mexico

David K. Stevenson, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Sheldon B. Korones, MD

Role: PRINCIPAL_INVESTIGATOR

University of Tennessee

Jon E. Tyson, MD MPH

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Seetha Shankaran, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Richard A. Ehrenkranz, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

W. Kenneth Poole, PhD

Role: PRINCIPAL_INVESTIGATOR

RTI International

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

RTI International

Durham, North Carolina, United States

Site Status

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Site Status

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

Cleveland, Ohio, United States

Site Status

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Site Status

University of Tennessee

Memphis, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 12219057 (View on PubMed)

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.

Reference Type RESULT
PMID: 11150359 (View on PubMed)

Related Links

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http://neonatal.rti.org

NICHD Neonatal Research Network

Other Identifiers

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U10HD034216

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD034167

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021397

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027853

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027871

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021415

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027881

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021385

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027880

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021373

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HD036790

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR008084

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR006022

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000750

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000997

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000070

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR001032

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NICHD-NRN-0018

Identifier Type: -

Identifier Source: org_study_id

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