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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05446272
Other study ID # 849912
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date August 3, 2022
Est. completion date March 31, 2027

Study information

Verified date February 2024
Source University of Pennsylvania
Contact Elizabeth Foglia
Phone 267-441-7144
Email FOGLIA@email.chop.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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


Recruitment information / eligibility

Status Recruiting
Enrollment 478
Est. completion date March 31, 2027
Est. primary completion date March 31, 2026
Accepts healthy volunteers No
Gender All
Age group 0 Days to 28 Days
Eligibility 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


Related Conditions & MeSH terms


Intervention

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.
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.

Locations

Country Name City State
Canada Mt Sinai Hospital Toronto
Canada BC Children's and Women's Hospital Vancouver
United States Nationwide Children's Hospital Columbus Ohio
United States Joe DiMaggio Children's Hospital Hollywood Florida
United States Peyton Manning Children's Hospital Indianapolis Indiana
United States Children's Mercy Hospital Kansas City Missouri
United States Arkansas Children's Hospital Little Rock Arkansas
United States Loma Linda University Loma Linda California
United States Norton Children's Hospital Louisville Kentucky
United States Intermountain Medical Center Murray Utah
United States AdventHealth Orlando Florida
United States Hospital of the University of Pennsylvania Philadelphia Pennsylvania
United States Utah Valley Hospital Provo Utah
United States Children's Hospital of Richmond Richmond Virginia
United States Washington University in St.Louis Saint Louis Missouri
United States Sharp Mary Birch San Diego California
United States Virtua Vorhees Hospital Voorhees New Jersey

Sponsors (2)

Lead Sponsor Collaborator
University of Pennsylvania National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Other 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). From randomization through 36 weeks PMA
Other 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. From randomization through 36 weeks PMA
Other 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. From randomization through 36 weeks PMA
Primary 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. within the first 5 days (120 hours) post extubation
Secondary 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. 36 weeks PMA
Secondary Death or BPD at 36 weeks PMA Composite dichotomous (y/n) outcome of death or grade 2/3 BPD, using the NRN criteria 36 weeks PMA
Secondary 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) 36 weeks PMA
Secondary Postmenstrual age at last invasive ventilation Time to cessation of invasive ventilation, with censoring at 36 weeks PMA 36 weeks PMA
Secondary Postmenstrual age at last positive pressure support Time to cessation of positive pressure respiratory support, with censoring at 36 weeks PMA 36 weeks PMA
Secondary Postmenstrual age at last supplemental oxygen Time to cessation of supplemental oxygen, with censoring at 36 weeks PMA 36 weeks PMA
Secondary 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 36 weeks PMA
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