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NCT Number: NCT05446272

The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial

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.

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Key information

Conditions

Extubation Failure Bronchopulmonary Dysplasia Congenital, Hereditary, and Neonatal Diseases and Abnormalities Death Infant, Newborn, Diseases Infant, Premature, Diseases Lung Diseases Lung Injury Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Ventilator-Induced Lung Injury

Age range

0 day–9 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

NIV-NAVA

Device

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: Non-invasive Neurally Adjusted Ventilatory Assist

NS-NIPPV

Device

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: Non-synchronized Non-invasive Positive Pressure Ventilation

Primary outcomes

  1. Extubation failure

    Time frame: 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 outcomes

  1. Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA

    Time frame: 36 weeks PMA

    BPD will be assessed as an ordinal outcome (none, grade 1, 2, 3), according to the NRN criteria.

  2. Death or BPD at 36 weeks PMA

    Time frame: 36 weeks PMA

    Composite dichotomous (y/n) outcome of death or grade 2/3 BPD, using the NRN criteria

  3. Endotracheal intubation through 36 weeks PMA

    Time frame: 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)

  4. Postmenstrual age at last invasive ventilation

    Time frame: 36 weeks PMA

    Time to cessation of invasive ventilation, with censoring at 36 weeks PMA

  5. Postmenstrual age at last positive pressure support

    Time frame: 36 weeks PMA

    Time to cessation of positive pressure respiratory support, with censoring at 36 weeks PMA

  6. Postmenstrual age at last supplemental oxygen

    Time frame: 36 weeks PMA

    Time to cessation of supplemental oxygen, with censoring at 36 weeks PMA

  7. Prematurity-related morbidities through 36 weeks PMA

    Time frame: 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 outcomes

  1. Death

    Time frame: 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).

  2. Air Leaks

    Time frame: 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.

  3. Gastrointestinal perforation or bleeding

    Time frame: 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.

  4. Regional distribution of lung aeration

    Time frame: From extubation through 5 days after extubation

    this will be measured with electrical impedance tomography in a subset of patients

  5. Mean airway pressure

    Time frame: From extubation through 5 days after extubation

    this will be measured from ventilator downloads for a subset of patients

  6. peak inflation pressure

    Time frame: From extubation through 5 days after extubation

    this will be measured from ventilator downloads for a subset of patients

  7. Edi signal

    Time frame: From extubation through 5 days after extubation

    this will be measured from ventilator downloads for a subset of patients

  8. Fio2

    Time frame: From extubation through 5 days after extubation

    this will be measured from ventilator downloads for a subset of patients

Study contacts

Contact information is provided by the study sponsor or research team.

Elizabeth Foglia

CONTACT

[email protected]

267-441-7144

Lisa Wesby, MS

CONTACT

[email protected]

215-573-6318

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Acronym: DIVA

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Jul 6, 2022
Registry last updated
Jun 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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