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

Not Applicable

Recruiting

• Conditions: ARDS
• Interventions: Other: Standard Ventilation Strategy; Other: Respiratory Mechanics

• Registration Number: NCT03963622
• Lead Sponsor: Unity Health Toronto

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.

Study Timeline

• Study First Submitted: 2019-05-06
• Study First Submitted QC: 2019-05-23
• Study First Posted: 2019-05-24
• Study Start: 2020-11-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-11
• Last Update Posted: 2024-11-13
• Primary Completion: 2025-11
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 740

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Standard Ventilation Strategy	Standard ventilation strategy.
Respiratory Mechanics	Respiratory Mechanics	The goal of this arm is to individualize tidal volume (VT) and PEEP according to respiratory mechanics.

Primary Outcome Measures

Name	Time	Method
All-cause 60-day mortality	60 days	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.

Secondary Outcome Measures

Name	Time	Method
Duration of ventilation	May exceed 60 days	Duration of ventilation in days
Duration of ICU and hospital stay	May exceed 60 days	Duration of ICU and hospital stay in days
Number of patients with organ dysfunction	Day 1-7, 14, 21, 28	Organ dysfunction as per the SOFA score
Mortality at ICU discharge, 28 days, and hospital discharge	Up to date of ICU discharge, 28 days, and hospital discharge	Mortality
Number of patients with barotrauma	Up to 60 days	Barotrauma defined as new onset of pneumothorax

Trial Locations

Locations (32)

St. Michael's Hospital; 🇨🇦 Toronto, Canada

Toronto General Hospital; 🇨🇦 Toronto, Canada

Toronto Western Hospital; 🇨🇦 Toronto, Canada

CHU Amiens-Picardie; 🇫🇷 Amiens, France

New York University Grossman School of Medicine; 🇺🇸 New York, New York, United States

Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC); 🇦🇷 Buenos Aires, Argentina

Complejo Médico Policía Federal Argentina Churruca Visca; 🇦🇷 Buenos Aires, Argentina

Hospital Británico de Buenos Aires; 🇦🇷 Buenos Aires, Argentina

Sanatorio Anchorena Recoleta; 🇦🇷 Buenos Aires, Argentina

Sanatorio Mater Dei; 🇦🇷 Buenos Aires, Argentina

Sanatorio Anchorena San Martín; 🇦🇷 San Martín, Argentina

Pontificia Universidad Católica de Chile; 🇨🇱 Santiago de Chile, Chile

Centre hospitalier universitaire d'Angers; 🇫🇷 Angers, France

CH Victor Dupouy; 🇫🇷 Argenteuil, France

CH de Beauvais; 🇫🇷 Beauvais, France

CHU Bordeaux - Haut Leveque; 🇫🇷 Bordeaux, France

Hopital de la Cavale Blanche - CHRU Brest; 🇫🇷 Brest, France

CH de Cholet; 🇫🇷 Cholet, France

Hopital Intercommunal de Creteil; 🇫🇷 Creteil, France

CHU Grenoble-Alpes; 🇫🇷 Grenoble, France

Hopital Roger Salengro - CHU Lille; 🇫🇷 Lille, France

Groupe Hospitalier de la Region de Mulhouse et Sud Alsace; 🇫🇷 Mulhouse, France

Hopital de l'Archet 1 - CHU de Nice; 🇫🇷 Nice, France

Hopital Europeen Georges-Pompidou; 🇫🇷 Paris, France

CHU de Poitiers - La Miletrie; 🇫🇷 Poitiers, France

CH Bretagne Atlantique Vannes-Auray; 🇫🇷 Vannes, France

HIA Robert Picque; 🇫🇷 Villenave-d'Ornon, France

Arcispedale Sant'Anna; 🇮🇹 Ferrara, Italy

University of Foggia; 🇮🇹 Foggia, Italy

Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Rome, Italy

L'Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Vall d'Hebron University Hospital; 🇪🇸 Barcelona, Spain