About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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)
Trial design
Parallel
Treatments tested in this trial
NIV-NAVA
DeviceInfants 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-NIPPV
DeviceInfants 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.
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
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.
Death or BPD at 36 weeks PMA
Composite dichotomous (y/n) outcome of death or grade 2/3 BPD, using the NRN criteria
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)
Postmenstrual age at last invasive ventilation
Time to cessation of invasive ventilation, with censoring at 36 weeks PMA
Other outcomes
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).
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.
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.
Regional distribution of lung aeration
this will be measured with electrical impedance tomography in a subset of patients
Sponsors and contacts
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University of Pennsylvania
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator