Extubation FailureDIVANCT05446272
The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial
A study testing NIV-NAVA and NS-NIPPV in people with Extubation Failure and Bronchopulmonary Dysplasia, run by University of Pennsylvania at 20 sites in 2 countries.
Trial summary
DIVA is a pragmatic randomized clinical trial (RCT) to determine: among (P) preterm infants born 23 0/7-28 6/7 weeks gestation undergoing extubation from mechanical ventilation, whether (I) Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) (C) compared with Non-synchronized nasal intermittent positive… Read more about this study
- Who is it for?
- Ages 0 days to 9 weeks
- Conditions the study is for
- Extubation Failure, Bronchopulmonary Dysplasia, Death
- What is being tested?
- NIV-NAVA and NS-NIPPV
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 478 participants
- Where
- 20 sitesin 2 countries
- Study dates
- 3 Aug 2022to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 0 days to 9 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Gestational age of 23 0/7- 28 6/7 weeks at birth
- Intubated in the first 7 days of life
- Undergoing extubation following at least 12 hours of invasive mechanical ventilation
- Post-natal age <32 weeks Post menstrual age at time of extubation
Who cannot join
- Major congenital anomalies, including pulmonary hypoplasia
- Neurologic disorders affecting respiratory drive (other than apnea of prematurity)
- Esophageal bleeding or other contraindication to NG/OG catheter placement
- Current weight <500 grams (based on Edi catheter approval)
- Study ventilator not available at time eligibility criteria are met
- Planned surgery or invasive procedure within 5 days of extubation
- Informed consent not provided
Trial locations and contacts
20 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
20 sites in 2 countries
United States17 sites, 16 recruiting
- Recruiting
Levine Children's Hospital
Charlotte, North Carolina, 28203
Eugenia Pallotto, Eugenia.Pallotto@atriumhealth.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Matthew Kielt
Matthew.Kielt@nationwidechildrens.org
- Recruiting
Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Bruce Shulman, brucesmd@icloud.com
- Recruiting
Peyton Manning Children's Hospital
Indianapolis, Indiana, 46260
Markus Tauscher, mktausc1@ascension.org
- Recruiting
Children's Mercy Hospital
Kansas City, Missouri, 64108
Christopher Nitkin, crnitkin@cmh.edu
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
David Matlock, DMatlock@uams.edu
- Terminated
Loma Linda University
Loma Linda, California, 92350
- Recruiting
Norton Children's Hospital
Louisville, Kentucky, 40202
Dan Stewart, dan.stewart@louisville.edu
- Recruiting
Intermountain Medical Center
Murray, Utah, 84107
Bradley Yoder, Bradley.Yoder@hsc.utah.edu
- Recruiting
AdventHealth
Orlando, Florida, 32803
Samarth Shukla, Samarth.Shukla.MD@AdventHealth.com
- Recruiting
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Elizabeth Foglia, FOGLIA@email.chop.edu
- Recruiting
Utah Valley Hospital
Provo, Utah, 84604
Bradley Yoder
Bradley.Yoder@hsc.utah.edu
- Recruiting
Children's Hospital of Richmond
Richmond, Virginia, 23219
Karen Hendrick-Munoz, karen.hendricks-munoz@vcuhealth.org
- Recruiting
Sharp Mary Birch
San Diego, California, 92123
Anup Katheria, Anup.Katheria@sharp.com
- Recruiting
Washington University in St.Louis
St Louis, Missouri, 63110
Roa Rakesh
rao_r@wustl.edu
- Recruiting
Virtua Vorhees Hospital
Voorhees Township, New Jersey, 08043
Sarvin Ghavam
ghavams@chop.edu
- Recruiting
Atrial Health Brenner Children's Hospital( Wake Forest)
Winston-Salem, North Carolina, 27157
Ricardo J Rodriguez, rjrodrig@wakehealth.edu
Canada3 sites, 3 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5
Maher Shahroor, maher.shahroor@sunnybrook.ca
- Recruiting
Mt Sinai Hospital
Toronto, ON M5G 1X5
Amish Jain, Amish.Jain@sinaihealth.ca
- Recruiting
BC Children's and Women's Hospital
Vancouver, BC V6H 3N1
Jonathan Wong, jonathan.wong@cw.bc.ca
About this study
DIVA is a pragmatic randomized clinical trial (RCT) to determine: among (P) preterm infants born 23 0/7-28 6/7 weeks gestation undergoing extubation from mechanical ventilation, whether (I) Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) (C) compared with Non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV), will reduce the incidence of (O) extubation failure within (T) 5 days (120 hours) of extubation.
Read the detailed description
Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and is the leading respiratory cause of childhood morbidity. Ventilator induced lung injury (VILI) an accepted and important contributor to BPD. Exposure to oxygen and positive pressure ventilation leads to developmental arrest and parenchymal injury in the immature preterm lung. Because even brief exposure to intubated positive pressure ventilation is injurious, avoiding invasive mechanical ventilation is the most widely acknowledged strategy to prevent VILI and the long-term sequela of BPD. Therefore, time on ventilators and rates of successful extubation are important endpoints of therapy.
Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is an FDA approved technology that consistently synchronizes non-invasive respiratory support with infant respiratory drive. The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial is an unblinded, pragmatic, multicenter phase III randomized clinical trial in extremely preterm infants 23 0/7- 28 6/7 weeks gestational age to determine if NIV-NAVA, compared with non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV), prevents extubation failure within 5 days (120 hours) of extubation from mechanical ventilation
- Conditions
- Extubation Failure, Bronchopulmonary Dysplasia, Death
- Being tested
- NIV-NAVA, NS-NIPPV
- Medical subject headings
- Bronchopulmonary Dysplasia, Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIV-NAVADevice
Also called Non-invasive Neurally Adjusted Ventilatory Assist
Infants in the intervention arm will be managed with non-invasive neurally adjusted ventilatory assist (NIV-NAVA) using FDA-approved servos with associated FDA-approved Edi catheter.
NS-NIPPVDevice
Also called Non-synchronized Non-invasive Positive Pressure Ventilation
Infants in the active comparator arm will be treated with non-synchronized non-invasive positive pressure ventilation (NIPPV) through FDA-approved ventilators currently in use at each site.
| Study group | Role | What they receive |
|---|---|---|
| NIV-NAVA | Experimental | Not described Receives: Device: NIV-NAVA |
| NS- NIPPV | Active comparator | Not described Receives: Device: NS-NIPPV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extubation failure
Extubation failure is defined when an infant is on the allocated mode of respiratory support and meets any of the following 4 criteria: (1) Rise in FiO2 at least 20% from pre-extubation value for >2 hours to maintain local SpO2 targets, (2) pH ≤7.20 or pCO2 ≥70mm Hg; (3) >1 apneic event requiring positive pressure ventilation (PPV) within 6 hours or ≥ 6 apneic events requiring stimulation within 6 hours (4) emergent intubation by the clinical team for cardiovascular instability or surgery.
Measured: within the first 5 days (120 hours) post extubation
Secondary outcomes (7)
Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA
BPD will be assessed as an ordinal outcome (none, grade 1, 2, 3), according to the NRN criteria.
Measured: 36 weeks PMA
Death or BPD at 36 weeks PMA
Composite dichotomous (y/n) outcome of death or grade 2/3 BPD, using the NRN criteria
Measured: 36 weeks PMA
Endotracheal intubation through 36 weeks PMA
Endotracheal intubation will be assessed 2 ways: As a dichotomous (y/n) outcome if it occurs at any time and also as days until endotracheal intubation (with censoring at 36 weeks PMA)
Measured: 36 weeks PMA
Postmenstrual age at last invasive ventilation
Time to cessation of invasive ventilation, with censoring at 36 weeks PMA
Measured: 36 weeks PMA
Postmenstrual age at last positive pressure support
Time to cessation of positive pressure respiratory support, with censoring at 36 weeks PMA
Measured: 36 weeks PMA
Postmenstrual age at last supplemental oxygen
Time to cessation of supplemental oxygen, with censoring at 36 weeks PMA
Measured: 36 weeks PMA
Prematurity-related morbidities through 36 weeks PMA
Brain injury (intraventricular hemorrhage and periventricular leukomalacia), patent ductus arteriosus requiring therapy, pulmonary hemorrhage, culture proven sepsis, necrotizing enterocolitis, retinopathy of prematurity
Measured: 36 weeks PMA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2022
- Study start3 Aug 2022
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Extubation FailureStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 478 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Elizabeth Foglia, Principal investigator, CHOP/UPENN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05446272
- Sponsor's protocol ID
- 849912
- Acronym
- DIVA
- Status last verified
- Jun 2026
- First submitted
- 28 Jun 2022
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Research records will be retained at each study site, and at the DCC for 3 years after completion of the study. We will follow NIH sharing policies with regards to sharing of data and specimens to public repositories, where appropriate
Publications
Matlock DN, Ratcliffe SJ, Courtney SE, Kirpalani H, Firestone K, Stein H, Dysart K, Warren K, Goldstein MR, Lund KC, Natarajan A, Demissie E, Foglia EE. The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation. Trials. 2024 Mar 20;25(1):201. doi: 10.1186/s13063-024-08038-4.
PubMed 38509583
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial
- ClinicalTrials.gov ID
- NCT05446272
- Acronym / sponsor ID
- DIVA / 849912
- Conditions
- Extubation Failure, Bronchopulmonary Dysplasia, Death
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 478 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 3 Aug 2022 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 6 Jul 2022 (actual)
- 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.
DIVA is a pragmatic randomized clinical trial (RCT) to determine: among (P) preterm infants born 23 0/7-28 6/7 weeks gestation undergoing extubation from mechanical ventilation, whether (I) Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) (C) compared with Non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV), will reduce the incidence of (O) extubation failure within (T) 5 days (120 hours) of extubation.
Detailed description
Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and is the leading respiratory cause of childhood morbidity. Ventilator induced lung injury (VILI) an accepted and important contributor to BPD. Exposure to oxygen and positive pressure ventilation leads to developmental arrest and parenchymal injury in the immature preterm lung. Because even brief exposure to intubated positive pressure ventilation is injurious, avoiding invasive mechanical ventilation is the most widely acknowledged strategy to prevent VILI and the long-term sequela of BPD. Therefore, time on ventilators and rates of successful extubation are important endpoints of therapy.
Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is an FDA approved technology that consistently synchronizes non-invasive respiratory support with infant respiratory drive. The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial is an unblinded, pragmatic, multicenter phase III randomized clinical trial in extremely preterm infants 23 0/7- 28 6/7 weeks gestational age to determine if NIV-NAVA, compared with non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV), prevents extubation failure within 5 days (120 hours) of extubation from mechanical ventilation
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NIV-NAVA | Experimental | Device: NIV-NAVA |
| NS- NIPPV | Active comparator | Device: NS-NIPPV |
Who may qualify
- Ages
- 0 days to 9 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Gestational age of 23 0/7- 28 6/7 weeks at birth
- Intubated in the first 7 days of life
- Undergoing extubation following at least 12 hours of invasive mechanical ventilation
- Post-natal age <32 weeks Post menstrual age at time of extubation
Key exclusion criteria (7 listed)
- Major congenital anomalies, including pulmonary hypoplasia
- Neurologic disorders affecting respiratory drive (other than apnea of prematurity)
- Esophageal bleeding or other contraindication to NG/OG catheter placement
- Current weight <500 grams (based on Edi catheter approval)
- Study ventilator not available at time eligibility criteria are met
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 |
|---|---|---|
| NIV-NAVAAlso: Non-invasive Neurally Adjusted Ventilatory AssistInfants in the intervention arm will be managed with non-invasive neurally adjusted ventilatory assist (NIV-NAVA) using FDA-approved servos with associated FDA-approved Edi catheter. | Device | NIV-NAVA |
| NS-NIPPVAlso: Non-synchronized Non-invasive Positive Pressure VentilationInfants in the active comparator arm will be treated with non-synchronized non-invasive positive pressure ventilation (NIPPV) through FDA-approved ventilators currently in use at each site. | Device | NS- NIPPV |
Primary outcome
Extubation failure
Time frame: within the first 5 days (120 hours) post extubation
Extubation failure is defined when an infant is on the allocated mode of respiratory support and meets any of the following 4 criteria: (1) Rise in FiO2 at least 20% from pre-extubation value for >2 hours to maintain local SpO2 targets, (2) pH ≤7.20 or pCO2 ≥70mm Hg; (3) >1 apneic event requiring positive pressure ventilation (PPV) within 6 hours or ≥ 6 apneic events requiring stimulation within 6 hours (4) emergent intubation by the clinical team for cardiovascular instability or surgery.
7 secondary outcomes
Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA
Time frame: 36 weeks PMA
Death or BPD at 36 weeks PMA
Time frame: 36 weeks PMA
Endotracheal intubation through 36 weeks PMA
Time frame: 36 weeks PMA
Postmenstrual age at last invasive ventilation
Time frame: 36 weeks PMA
Postmenstrual age at last positive pressure support
Time frame: 36 weeks PMA
Postmenstrual age at last supplemental oxygen
Time frame: 36 weeks PMA
Prematurity-related morbidities through 36 weeks PMA
Time frame: 36 weeks PMA
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Derived from this study: PubMed 38509583Matlock DN, Ratcliffe SJ, Courtney SE, Kirpalani H, Firestone K, Stein H, Dysart K, Warren K, Goldstein MR, Lund KC, Natarajan A, Demissie E, Foglia EE. The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation. Trials. 2024 Mar 20;25(1):201. doi: 10.1186/s13063-024-08038-4.
- Individual participant dataSharing planned: Yes. Research records will be retained at each study site, and at the DCC for 3 years after completion of the study. We will follow NIH sharing policies with regards to sharing of data and specimens to public repositories, where appropriate
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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.
Elizabeth Foglia principal investigator
CHOP/UPENN
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NIV-NAVA and NS-NIPPV in people with Extubation Failure and Bronchopulmonary Dysplasia, run by University of Pennsylvania at 20 sites in 2 countries.
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 4 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elizabeth Foglia (267-441-7144, FOGLIA@email.chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extubation failure (time frame: within the first 5 days (120 hours) post extubation). 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 NCT05446272, which also lists 1 linked publication.
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 25 Jun 2026.