Extubation Failure, Bronchopulmonary Dysplasia, Death
Conditions
Brief 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 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
Interventions
DEVICENIV-NAVA
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.
DEVICENS-NIPPV
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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
Trial PIs are unaware of treatment allocation for individual subjects
Eligibility
Sex/Gender
ALL
Age
0 Days to 9 Weeks
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extubation failure | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA | 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 | 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 | 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 | 36 weeks PMA | Time to cessation of invasive ventilation, with censoring at 36 weeks PMA |
| Postmenstrual age at last positive pressure support | 36 weeks PMA | Time to cessation of positive pressure respiratory support, with censoring at 36 weeks PMA |
| Postmenstrual age at last supplemental oxygen | 36 weeks PMA | Time to cessation of supplemental oxygen, with censoring at 36 weeks PMA |
| Prematurity-related morbidities through 36 weeks PMA | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal perforation or bleeding | From randomization through 36 weeks PMA | 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. |
| Death | From randomization through 36 weeks PMA | 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 | From randomization through 36 weeks PMA | 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. |
| Regional distribution of lung aeration | From extubation through 5 days after extubation | this will be measured with electrical impedance tomography in a subset of patients |
| Mean airway pressure | From extubation through 5 days after extubation | this will be measured from ventilator downloads for a subset of patients |
| peak inflation pressure | From extubation through 5 days after extubation | this will be measured from ventilator downloads for a subset of patients |
| Edi signal | From extubation through 5 days after extubation | this will be measured from ventilator downloads for a subset of patients |
| Fio2 | From extubation through 5 days after extubation | this will be measured from ventilator downloads for a subset of patients |
Countries
Canada, United States
Contacts
Primary ContactElizabeth Foglia
Backup ContactLisa Wesby, MS
Outcome results
None listed