The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial
Study Details
Study Description
Brief Summary
DIVA is a pragmatic randomized clinical trial (RCT) to determine: among (P) preterm infants born 24-27 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 240/7- 276/7 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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NIV-NAVA
|
Device: NIV-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.
Other Names:
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| Active Comparator: NS- NIPPV
|
Device: NS-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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Gestational age of 24-27 6/7 weeks at birth
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Intubated in the first 7 days of life
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Undergoing extubation following at least 12 hours of invasive mechanical ventilation
-
Post-natal age <28 days at time of extubation
Exclusion Criteria:
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Major congenital anomalies, including pulmonary hypoplasia
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Neurologic disorders affecting respiratory drive (other than apnea of prematurity)
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Esophageal bleeding or other contraindication to NG/OG catheter placement
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Current weight <500 grams (based on Edi catheter approval)
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Study ventilator not available at time eligibility criteria are met
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Planned surgery or invasive procedure within 5 days of extubation
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Informed consent not provided
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202 |
| 2 | Loma Linda University | Loma Linda | California | United States | 92350 |
| 3 | Sharp Mary Birch | San Diego | California | United States | 92123 |
| 4 | Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
| 5 | Peyton Manning Children's Hospital | Indianapolis | Indiana | United States | 46260 |
| 6 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
| 7 | Children's Mercy Hospital | Kansas City | Missouri | United States | 64108 |
| 8 | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 9 | University of Utah Health Science Center | Salt Lake City | Utah | United States | 84132 |
| 10 | Children's Hospital of Richmond | Richmond | Virginia | United States | 23219 |
| 11 | Mt Sinai Hospital | Toronto | Canada | ON M5G 1X5 | |
| 12 | BC Children's and Women's Hospital | Vancouver | Canada | BC V6H 3N1 |
Sponsors and Collaborators
- University of Pennsylvania
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Elizabeth Foglia, CHOP/UPENN
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 849912