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

ARDS Clinical Trial

— CAVIARDS  

Official title:

Careful Ventilation in Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03963622
• Other study ID #: 1765
• Status: Recruiting
• Phase: N/A
• Start date: November 23, 2020
• Est. completion date: November 2024

Study information

• Verified date: December 2022
• Source: Unity Health Toronto
• Contact: Laurent Brochard, MD
• Phone: 416-864-6060
• Email: laurent.brochard[@]unityhealth.to
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 740
• Est. completion date: November 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• ARDS
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Other:
• Respiratory Mechanics
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
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.

Locations

Country	Name	City	State
Argentina	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
Canada	St. Michael's Hospital	Toronto
Canada	Toronto General Hospital	Toronto
Canada	Toronto Western Hospital	Toronto
Chile	Pontificia Universidad Católica de Chile	Santiago de Chile
France	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
Italy	Arcispedale Sant'Anna	Ferrara
Italy	University of Foggia	Foggia
Italy	Policlinico Universitario Agostino Gemelli IRCCS	Rome
Spain	L'Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Vall d'Hebron University Hospital	Barcelona
United States	New York University Grossman School of Medicine	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Unity Health Toronto	Applied Health Research Centre, Canadian Institutes of Health Research (CIHR), University of Toronto

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Baseline, 24 and 72 hours
Primary	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.	60 days
Secondary	Duration of ventilation	Duration of ventilation in days	May exceed 60 days
Secondary	Duration of ICU and hospital stay	Duration of ICU and hospital stay in days	May exceed 60 days
Secondary	Number of patients with organ dysfunction	Organ dysfunction as per the SOFA score	Day 1-7, 14, 21, 28
Secondary	Number of patients with barotrauma	Barotrauma defined as new onset of pneumothorax	Up to 60 days
Secondary	Mortality at ICU discharge, 28 days, and hospital discharge	Mortality	Up to date of ICU discharge, 28 days, and hospital discharge

External Links

•   Study website