The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial

Not Applicable

Recruiting

• Conditions: Extubation Failure; Bronchopulmonary Dysplasia; Death

• Registration Number: NCT05446272
• Lead Sponsor: University of Pennsylvania

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.

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 Timeline

• Study First Submitted: 2022-06-28
• Study First Submitted QC: 2022-06-28
• Study First Posted: 2022-07-06
• Study Start: 2022-08-03
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-13
• Last Update Posted: 2025-06-15
• Primary Completion: 2026-10-31
• Study Completion: 2027-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 478

Inclusion Criteria

• Gestational age of 24-27 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 <28 days 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 supplemental oxygen	36 weeks PMA	Time to cessation of supplemental oxygen, 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
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

Trial Locations

Locations (20)

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Loma Linda University; 🇺🇸 Loma Linda, California, United States

Sharp Mary Birch; 🇺🇸 San Diego, California, United States

Joe DiMaggio Children's Hospital; 🇺🇸 Hollywood, Florida, United States

AdventHealth; 🇺🇸 Orlando, Florida, United States

Peyton Manning Children's Hospital; 🇺🇸 Indianapolis, Indiana, United States

Norton Children's Hospital; 🇺🇸 Louisville, Kentucky, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

Washington University in St.Louis; 🇺🇸 Saint Louis, Missouri, United States

Virtua Vorhees Hospital; 🇺🇸 Voorhees, New Jersey, United States

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