Domain Lead Investigators
Domain Protocol Committee Members
Resources
- Download 1. IMV Strategies Protocol Summary (pdf:187KB)
- Download 2. IMV Strategies Domain Protocol (pdf:1.5MB)
Domain Description
Objective | The primary objective for the domain is to identify the invasive mechanical ventilation strategy that most effectively improves patient outcomes among a range of strategies including best conventional mechanical ventilation. This overarching primary objective will apply to all interventions being evaluated in phase III. For interventions being evaluated at the pilot and feasibility phase or at phase II, there will be comparison-specific primary objectives defined in the statistical analysis section. |
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Population | This domain will enroll patients receiving invasive mechanical ventilation for early acute hypoxemic respiratory failure (PaO2:FiO2 < 300 mm Hg, <72 hours) in three of the four platform-defined states: low elastance, high elastance, or extracorporeal life support |
Primary Endpoint | Ventilator-free days to day 28 |
Design | Interventions in this domain will be evaluated at various stages including pilot/feasibility evaluations, phase II, or phase III. Interventions evaluated at phase II will be compared to other groups in the domain according to specified endpoints of interest. Interventions evaluated at phase III will be compared to all other groups in the domain being evaluated at phase III to determine superiority or futility on the domain primary endpoint. Superiority is defined as >99.25% probability of odds ratio >1 for ventilator-free days. Futility is defined as >90% probability of odds ratio <1.2 for ventilator-free days. |
Interventions
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Intervention Lead investigators Eligible states - Low elastance (invasively ventilated)
- High elastance (invasively ventilated)
Description - Tidal volume and positive end-expiratory pressure adjusted to maintain static airway driving pressure <15 cm H2O (during passive ventilation) and dynamic transpulmonary driving pressure < 23 cm H2O (during assisted ventilation)
- Plateau airway pressure <35 cm H2O
Stage of evaluation Phase III Primary endpoint Ventilator-free days to day 28
Active comparator Conventional lung-protective ventilation
Target sample size Adapted based on pre-specified stopping rules defining superiority and futility. Maximum sample size of 2,000 patients. Participating sites All sites participating in this domain -
Intervention Lead investigators Eligible states - Low elastance (invasively ventilated)
- High elastance (invasively ventilated)
- Extracorporeal life support
Description - Ventilation and sedation adjusted to maintain
- Static airway driving pressure ≤15 cm H2O (during passive ventilation)
- Dynamic transpulmonary driving pressure <23 cm H2O (during assisted ventilation)
- Moderate respiratory effort (Pocc –6 to –20 cm H2O)
Stage of evaluation Phase II Primary endpoint - Protocol adherence
- Probability of achieving lung- and diaphragm-protective targets
Active comparator - Conventional lung-protective ventilation
- Driving pressure-limited ventilation
Target sample size 50 patients Participating sites Up to 8 centers participating in this domain -
Intervention Lead investigators Eligible states Description - Tidal volume target of 6 mL/kg predicted body weight
- Plateau airway pressure <30 cm H2O
Stage of evaluation Primary endpoint Active comparator Target sample size Perpetual until clinical inferiority established in comparison to any other intervention in the domain Participating sites All sites participating in this domain -
Intervention Lead investigators Eligible states Description This is a multicenter randomized controlled clinical trial with an adaptive design assessing the efficacy of setting the ventilator based on measurements of respiratory mechanics (recruitability and effort) to reduce Day 60 mortality in patients with acute respiratory distress syndrome (ARDS).
The CAVIARDS study is also a basket trial; a basket trial design examines a single intervention in multiple disease populations. CAVIARDS consists of an identical 2-arm mechanical ventilation protocol implemented in two different study populations (COVID-19 and non-COVID-19 patients). As per a typical basket trial design, the operational structure of both the COVID-19 substudy (CAVIARDS-19) and non-COVID-19 substudy (CAVIARDS-all) is shared (recruitment, procedures, data collection, analysis, management, etc.).
Stage of evaluation Not applicable Primary endpoint All-cause 60-day mortality: The lack of an appropriate surrogate endpoint, and the high baseline mortality rate mandate a multicentre RCT to determine the mortality effects of setting the ventilator based on recruitability and effort compared with conventional ventilation.
Active comparator CAVIARDS consists of an identical 2-arm mechanical ventilation protocol implemented in two different study populations (COVID-19 and non-COVID-19 patients).
Target sample size 740 patients Participating sites 32 to date (see https://clinicaltrials.gov/study/NCT03963622?term=CAVIARDS&rank=1 for details)