Health TrialsbyHealthPanel

Careful Ventilation in Acute Respiratory Distress Syndrome (COVID-19 and Non-COVID-19)

ConditionARDS
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUnity Health Toronto

About this trial

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.).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 y

Moderate or severe ARDS (PaO2/FiO2 ≤ 200 mmHg) within 48 h of meeting Berlin ARDS criteria (Patients who were eligible at the time of screening and whose PaO2/FiO2 became > 200 mm Hg under prone positioning when starting the protocol remained eligible)

Disqualifiers

Received continuous mechanical ventilation > 7 days

Known or clinically suspected elevated intracranial pressure (>18mmHg) necessitating strict control of PaCO2

Known pregnancy

Broncho-pleural fistula

Trial design

Design model

Parallel

Treatments tested in this trial

  • Respiratory Mechanics

    Other intervention

    Different maneuvers based on respiratory mechanics will be assessed at the bedside and will be used to individualize ventilator parameters. Recruitability will be assessed with a one breath decremental PEEP maneuver, and search for airway closure with a low-flow pressure volume or pressure-time curve. If the patient has airway closure, the minimal PEEP will be set at the airway opening pressure to avoid closure. If the patient is considered recruitable, the goal is to set PEEP at or above 15cmH20 to maximize alveolar recruitment, until the plateau pressure reaches the safety limit. Volume control ventilation at 6ml·kg-1 will be used. Once spontaneous breathing has started, the occlusion pressure (P0.1) will be maintained within targets.

  • Standard Ventilation Strategy

    Other intervention

    Patients randomized to the control arm will receive standard care. The PEEP is adjusted for oxygenation based on a PEEP-FiO2 table, either the low PEEP-FiO2 or the high PEEP-FiO2 table. Volume targeted ventilation with initial VT 6 mL·kg-1 and Plateau pressure at 30 cmH2O or below, targeting PaO2 60-80 or SpO2 90-95%, adjusted as per the protocol. Pressure-support ventilation is at physician's discretion, but recommended when FiO2 \<60%, and is titrated VT 6-8 mL·kg-1.

Treatment groups

740 Participants
are divided into 2 treatment groups
Group A: ControlActive comparator 1 intervention
Group B: Respiratory MechanicsExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
60 days

Secondary outcomes

1

Duration of ventilation

Duration of ventilation in days

Time frame
May exceed 60 days
2

Duration of ICU and hospital stay

Duration of ICU and hospital stay in days

Time frame
May exceed 60 days
3

Number of patients with organ dysfunction

Organ dysfunction as per the SOFA score

Time frame
Day 1-7, 14, 21, 28
4

Number of patients with barotrauma

Barotrauma defined as new onset of pneumothorax

Time frame
Up to 60 days

Other outcomes

1

The change in biomarker expression

Biomarkers include interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor receptor 1 (TNFr1), soluble receptor of the advanced glycation end products (sRAGE), and surfactant protein D (SPD). All measured in pg/ml

Time frame
Baseline, 24 and 72 hours

Sponsors and contacts

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Unity Health Toronto

Lead sponsor

Canadian Institutes of Health Research (CIHR)

Collaborator

University of Toronto

Collaborator

Applied Health Research Centre

Collaborator

Source ClinicalTrials.gov
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