Bronchopulmonary DysplasiaPhase 3SAVENCT00005777

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

A Phase 3 study testing Minimal mechanical ventilation management, Routine mechanical ventilation management and Dexamethasone in people with Bronchopulmonary Dysplasia and Respiratory Distress Syndrome, run by NICHD Neonatal Research Network at 13 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 5 minutes to 10 days
Conditions the study is for: Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Infant, Newborn
What is being tested?: Minimal mechanical ventilation management, Routine mechanical ventilation management and Dexamethasone
Type of treatment: Pill or oral medicine, Injection or infusion, Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 220 participants
Where: 13 sitesUnited States
Study dates: Feb 1998to Sep 2002
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 5 minutes to 10 days
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

United States13 sites

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

Other trials in United States

About this study

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

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.

Read the 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.

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: Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature
Being tested: Minimal mechanical ventilation management, Routine mechanical ventilation management, Dexamethasone, Placebo
Keywords: NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Chronic Lung Disease (CLD), Dexamethasone, Glucocorticoids, Respiration, Artificial, Mechanical ventilation, Respiratory Insufficiency
Medical subject headings: Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Premature Birth, Respiratory Aspiration, Respiratory Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Minimal mechanical ventilation managementProcedure or surgery
Partial pressure of carbon dioxide (PCO2) target (>52 mm Hg)
Routine mechanical ventilation managementProcedure or surgery
Partial pressure of carbon dioxide (PCO2) target <48 mm Hg)
DexamethasoneDrug
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.
PlaceboDrug
Also called Saline
The infants in the placebo groups received equal volumes of saline.

Study groups in NCT00005777
Study group	Role	What they receive
Minimal ventilation with Dexamethasone	Experimental	Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy Receives: Procedure: Minimal mechanical ventilation management; Drug: Dexamethasone
Minimal Ventilation without Dexamethasone	Experimental	Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy Receives: Procedure: Minimal mechanical ventilation management; Drug: Placebo
Routine ventilation with Dexamethasone	Active comparator	Not described Receives: Procedure: Routine mechanical ventilation management; Drug: Dexamethasone
Routine ventilation without Dexamethasone	Active comparator	Not described Receives: Procedure: Routine mechanical ventilation management; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Death or moderate to severe bronchopulmonary dysplasia
Measured: 36 weeks postmenstrual age

Secondary outcomes (20)

Death
Measured: 36 weeks postmenstrual age
Mechanical ventilation
Measured: 36 weeks postmenstrual age
Pulmonary interstitial emphysema
Measured: 36 weeks postmenstrual age
Pneumothorax
Measured: 36 weeks postmenstrual age
Open-label steroids
Measured: 36 weeks postmenstrual age
Reintubation
Measured: 36 weeks postmenstrual age
Intracranial hemorrhage (IVH) III or IV
Measured: 36 weeks postmenstrual age
Periventricular leukomalacia
Measured: 36 weeks postmenstrual age
Necrotizing enterocolitis
Measured: 36 weeks postmenstrual age
Duration of oxygen supplementation
Measured: 36 weeks postmenstrual age
Duration of ventilation
Measured: 36 weeks postmenstrual age
Length of hospitalization
Measured: Hospital discharge
Death or neurodevelopmental impairment
Measured: 18-22 months corrected age
Death
Measured: 18-22 months corrected age
Neurodevelopmental impairment
Measured: 18-22 months corrected age
Cerebral palsy
Measured: 18-22 months corrected age
Bilateral blindness
Measured: 18-22 months corrected age
Deafness
Measured: 18-22 months corrected age
Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI)
Measured: 18-22 months corrected age
Rehospitalizations
Measured: 18-22 months corrected age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 1998Sep 2002

First posted2 Jun 2000 (estimated)
Study startFeb 1998
Primary completionSep 1998
Study completionSep 2002

Why it stopped: The trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 220 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00005777
Sponsor's protocol ID: NICHD-NRN-0018
Other IDs: U10HD034216, U10HD034167, U10HD021397, U10HD027853, U10HD027871, U10HD021415, U10HD027904, U10HD027881
Acronym: SAVE
Status last verified: Jun 2015
First submitted: 1 Jun 2000
Last updated: 8 Jun 2015
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 12219057
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.
PubMed 11150359

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
Recruiting
Controlled Remote Monitoring and Optimization of Oxygen Therapy in Preterm Infants
BPD - Bronchopulmonary Dysplasia, Pulmonary Hypertension
Not yet recruitingPhase 1/2
Little Lungs Study
Invasive Mechanical Ventilation, Severe Respiratory Distress Syndrome
Not yet recruiting
Strap To Reduce Apnea in Preterm Infants: A Randomized Crossover Trial
Apnea of Prematurity, Intermittent Hypoxemia
Recruiting
Ventilator Pressure and Optimization of Compliance and Hemodynamics
Bronchopulmonary Dysplasia, Pulmonary Hypertension Due to Lung Diseases and Hypoxia

All Bronchopulmonary Dysplasia trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00005777
Acronym / sponsor ID: SAVE / NICHD-NRN-0018
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
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: The trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy.
Enrolment: 220 participants (actual)
Lead sponsor: NICHD Neonatal Research NetworkResearch network
Collaborators: National Center for Research Resources (NCRR)
Study start: Feb 1998
Primary completion: Sep 1998 (actual)
Study completion: Sep 2002 (actual)
First posted: 2 Jun 2000 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Neurodevelopment was assessed at 18-22 months postmenstrual age.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Minimal ventilation with Dexamethasone	Experimental	Procedure: Minimal mechanical ventilation management, Drug: DexamethasoneMinimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy
Minimal Ventilation without Dexamethasone	Experimental	Procedure: Minimal mechanical ventilation management, Drug: PlaceboMinimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy
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

Who may qualify

Ages: 5 minutes to 10 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Minimal mechanical ventilation managementPartial pressure of carbon dioxide (PCO2) target (>52 mm Hg)	Procedure or surgery	Minimal Ventilation without Dexamethasone, Minimal ventilation with Dexamethasone
Routine mechanical ventilation managementPartial pressure of carbon dioxide (PCO2) target <48 mm Hg)	Procedure or surgery	Routine ventilation with Dexamethasone, Routine ventilation without Dexamethasone
DexamethasoneTreatment 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.	Drug	Minimal ventilation with Dexamethasone, Routine ventilation with Dexamethasone
PlaceboAlso: SalineThe infants in the placebo groups received equal volumes of saline.	Drug	Minimal Ventilation without Dexamethasone, Routine ventilation without Dexamethasone

Primary outcome

Death or moderate to severe bronchopulmonary dysplasia
Time frame: 36 weeks postmenstrual age

20 secondary outcomes

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

Results and safety

The study was stopped early (reason given: The trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
Results publication: PubMed 12219057Carlo 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.
Results publication: PubMed 11150359Stark 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.
NICHD Neonatal Research NetworkLink provided by the sponsor.

Related trials for Bronchopulmonary Dysplasia

Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
Recruiting
Controlled Remote Monitoring and Optimization of Oxygen Therapy in Preterm Infants
BPD - Bronchopulmonary Dysplasia, Pulmonary Hypertension
Not yet recruitingPhase 1/2
Little Lungs Study
Invasive Mechanical Ventilation, Severe Respiratory Distress Syndrome
Not yet recruiting
Strap To Reduce Apnea in Preterm Infants: A Randomized Crossover Trial
Apnea of Prematurity, Intermittent Hypoxemia
Recruiting
Ventilator Pressure and Optimization of Compliance and Hemodynamics
Bronchopulmonary Dysplasia, Pulmonary Hypertension Due to Lung Diseases and Hypoxia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Waldemar A. Carlo, MD study director

University of Alabama at Birmingham

Ann R. Stark, MD study director

Brigham and Women's Hospital

William Oh, MD principal investigator

Brown University, Women & Infants Hospital

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Death or moderate to severe bronchopulmonary dysplasia (time frame: 36 weeks postmenstrual age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00005777, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2015.