The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial

Bronchopulmonary Dysplasia Clinical Trial

— DIVA  

Official title:

The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05446272
• Other study ID #: 849912
• Status: Recruiting
• Phase: N/A
• 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
• 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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Death
• Extubation Failure

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