Clinical trial NCT03963622: Careful Ventilation in Acute Respiratory Distress Syndrome (COVID-19 and Non-COVID-19)
Official title: Careful Ventilation in Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ARDS
Keywords: Ventilation
ARDS
Airway closure
Lung recruitment
COVID-19
Basket trial
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: University of Toronto
name: Applied Health Research Centre
First posted: 2019-05-24
Enrollment: 740
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is also a basket design, which examines a single intervention in multiple disease populations. This basket trial consists of an identical 2-arm mechanical ventilation protocol implemented in two different study populations (patients with COVID-19-induced ARDS, and patients with all ARDS not induced by COVID-19). The protocol and procedures are identical between the two study populations in this basket trial.
Primary purpose: TREATMENT

Brief summary: 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.).

Detailed description: Acute respiratory distress syndrome (ARDS) is a major public health problem affecting approximately 10% of patients in the intensive care unit (ICU) and 23% of all patients on a breathing machine (mechanical ventilator). The short-term mortality of patients with ARDS is approximately 40% and better ventilation of these patients has the greatest potential to improve outcomes.

The lungs in patients with ARDS are severely inflamed which reduces lung volume and their ability to stretch, making ventilation difficult and dangerous. However, mechanical ventilation is the mainstay of supportive therapy. Although it is life-saving, it can also can generate secondary injury and inflammation, called ventilator-induced lung injury (VILI). The investigators know that inadequate mechanical ventilation worsens outcomes but are uncertain of the optimal way to manage ventilators at the bedside.

Furthermore, ARDS is challenging because there is no treatment for the alveolar-capillary leak characterizing this syndrome; aside from treating the underlying cause, the only supportive therapy is mechanical ventilation. This is specially the case for COVID-19 induced ARDS. Despite best practices, over-distension of the lung or inappropriate positive end expiratory pressure (PEEP) is common. Finally, once spontaneous breathing has resumed and is assisted by the ventilator, an additional phenomenon occurs, called patient self-inflicted lung injury. The drive for breathing in many patients is stimulated by lung inflammation, and strong breathing efforts can generate high distending pressures, causing lung (and systemic) inflammation and organ damage. Whether the management of COVID-19 induced ARDS should differ from all other ARDS has been debated at length but has no clear response

Recent advances in our understanding of bedside physiology (airway closure, recruitability, lung distension, respiratory drive) can now be applied for an individual titration of mechanical ventilation.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 y
2. Moderate or severe ARDS (PaO2/FiO2 ≤ 200 mmHg) within 48 h of meeting Berlin ARDS criteria

Exclusion Criteria:

1. Received continuous mechanical ventilation \> 7 days
2. Known or clinically suspected elevated intracranial pressure (\>18mmHg) necessitating strict control of PaCO2
3. Known pregnancy
4. Broncho-pleural fistula
5. Severe liver disease (Child-Pugh Score ≥ 10)
6. BMI \>40kg/m2
7. Anticipating withdrawal of life support and/or shift to palliation as the goal of care
8. Patient is receiving ECMO at time of randomization

Primary outcomes:
measure: All-cause 60-day mortality
timeFrame: 60 days
Secondary outcomes:
measure: Duration of ventilation
timeFrame: May exceed 60 days
measure: Duration of ICU and hospital stay
timeFrame: May exceed 60 days
measure: Number of patients with organ dysfunction
timeFrame: Day 1-7, 14, 21, 28
measure: Number of patients with barotrauma
timeFrame: Up to 60 days
measure: Mortality at ICU discharge, 28 days, and hospital discharge
timeFrame: Up to date of ICU discharge, 28 days, and hospital discharge
Other outcomes:
measure: The change in biomarker expression
timeFrame: Baseline, 24 and 72 hours
Locations:
city: New York
country: United States
facility: New York University Grossman School of Medicine
state: New York
city: Buenos Aires
country: Argentina
facility: Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)
city: Buenos Aires
country: Argentina
facility: Complejo Médico Policía Federal Argentina Churruca Visca
city: Buenos Aires
country: Argentina
facility: Hospital Británico de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Sanatorio Anchorena Recoleta
city: Buenos Aires
country: Argentina
facility: Sanatorio Mater Dei
city: San Martín
country: Argentina
facility: Sanatorio Anchorena San Martín
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Toronto
country: Canada
facility: Toronto Western Hospital
city: Santiago de Chile
country: Chile
facility: Pontificia Universidad Católica de Chile
city: Amiens
country: France
facility: CHU Amiens-Picardie
city: Angers
country: France
facility: Centre hospitalier universitaire d'Angers
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Beauvais
country: France
facility: CH de Beauvais
city: Bordeaux
country: France
facility: CHU Bordeaux - Haut Leveque
city: Brest
country: France
facility: Hopital de la Cavale Blanche - CHRU Brest
city: Cholet
country: France
facility: CH de Cholet
city: Creteil
country: France
facility: Hopital Intercommunal de Creteil
city: Grenoble
country: France
facility: CHU Grenoble-Alpes
city: Lille
country: France
facility: Hopital Roger Salengro - CHU Lille
city: Mulhouse
country: France
facility: Groupe Hospitalier de la Region de Mulhouse et Sud Alsace
city: Nice
country: France
facility: Hopital de l'Archet 1 - CHU de Nice
city: Paris
country: France
facility: Hopital Europeen Georges-Pompidou
city: Poitiers
country: France
facility: CHU de Poitiers - La Miletrie
city: Vannes
country: France
facility: CH Bretagne Atlantique Vannes-Auray
city: Villenave-d'Ornon
country: France
facility: HIA Robert Picque
city: Ferrara
country: Italy
facility: Arcispedale Sant'Anna
city: Foggia
country: Italy
facility: University of Foggia
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli IRCCS
city: Barcelona
country: Spain
facility: L'Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
Study officials:
affiliation: Unity Health Toronto
name: Laurent Brochard, MD
role: PRINCIPAL_INVESTIGATOR
References: