An interventional study of NIV-NAVA and NS-NIPPV in Extubation Failure, Bronchopulmonary Dysplasia and Death, sponsored by University of Pennsylvania. Recruiting at 20 sites in 2 countries. Open to participants aged 0 Days to 9 Weeks. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by University of Pennsylvania · Not applicable, Interventional, and Treatment
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.
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
362 studies on the registry are indexed under Bronchopulmonary Dysplasia; 85 are open to participants now.
This study's planned enrollment of 478 is above the median of 66 across 244 interventional studies indexed under Bronchopulmonary Dysplasia.
Browse Bronchopulmonary Dysplasia studies →University of Pennsylvania is the lead sponsor of 1,668 studies on the registry; 235 are open to participants now.
Of its 158 completed or terminated interventional studies of FDA-regulated products, 109 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Device: NIV-NAVA
Device: NS-NIPPV
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.
Also known as: Non-invasive Neurally Adjusted Ventilatory Assist
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.
Also known as: Non-synchronized Non-invasive Positive Pressure Ventilation
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.
Time frame: within the first 5 days (120 hours) post extubation
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.
Time frame: 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
Time frame: 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)
Time frame: 36 weeks PMA
Postmenstrual age at last invasive ventilation
Time to cessation of invasive ventilation, with censoring at 36 weeks PMA
Time frame: 36 weeks PMA
Postmenstrual age at last positive pressure support
Time to cessation of positive pressure respiratory support, with censoring at 36 weeks PMA
Time frame: 36 weeks PMA
Postmenstrual age at last supplemental oxygen
Time to cessation of supplemental oxygen, with censoring at 36 weeks PMA
Time frame: 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
Time frame: 36 weeks PMA
Death
Death will be measured in two ways (1) as a dichotomous (y/n) outcome if death occurs prior to 36 weeks PMA, and (2) days until death (with censoring at 36 weeks PMA).
Time frame: From randomization through 36 weeks PMA
Air Leaks
Air leaks will be measured as a dichotomous (y/n) outcome if a new pulmonary interstitial emphysema or pneumothorax occurs at any time after randomization until 36 weeks PMA.
Time frame: From randomization through 36 weeks PMA
Gastrointestinal perforation or bleeding
This will be measured as a dichotomous (y/n) outcome if a new GI perforation or bleeding occurs at any time after randomization until 36 weeks PMA.
Time frame: From randomization through 36 weeks PMA
Regional distribution of lung aeration
this will be measured with electrical impedance tomography in a subset of patients
Time frame: From extubation through 5 days after extubation
Mean airway pressure
this will be measured from ventilator downloads for a subset of patients
Time frame: From extubation through 5 days after extubation
peak inflation pressure
this will be measured from ventilator downloads for a subset of patients
Time frame: From extubation through 5 days after extubation
Edi signal
this will be measured from ventilator downloads for a subset of patients
Time frame: From extubation through 5 days after extubation
Fio2
this will be measured from ventilator downloads for a subset of patients
Time frame: From extubation through 5 days after extubation
Not enrolling at this site.
Plan to share: 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
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: 3 years after completion of the study
Started Aug 2022 (actual). Primary completion is estimated for Mar 2027, 55 months after the start.
Of 71 non-industry interventional studies with no phase under Bronchopulmonary Dysplasia, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 56. This study's planned 55 months is above that.
Counting every sponsor, half of 73 studies reached it within 37 months; a quarter within 19 and three quarters within 63.
How these figures are worked out, and which studies are left out of them.
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