NCT03963622

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.).

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
740

participants targeted

Target at P75+ for not_applicable

Timeline
4mo left

Started Nov 2020

Longer than P75 for not_applicable

Geographic Reach
8 countries

33 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress95%
Nov 2020Sep 2026

First Submitted

Initial submission to the registry

May 6, 2019

Completed
18 days until next milestone

First Posted

Study publicly available on registry

May 24, 2019

Completed
1.5 years until next milestone

Study Start

First participant enrolled

November 23, 2020

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2026

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2026

Last Updated

January 16, 2026

Status Verified

January 1, 2026

Enrollment Period

5.5 years

First QC Date

May 6, 2019

Last Update Submit

January 14, 2026

Conditions

Keywords

VentilationARDSAirway closureLung recruitmentCOVID-19Basket trial

Outcome Measures

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.

    60 days

Secondary Outcomes (5)

  • Duration of ventilation

    May exceed 60 days

  • Duration of ICU and hospital stay

    May exceed 60 days

  • Number of patients with organ dysfunction

    Day 1-7, 14, 21, 28

  • Number of patients with barotrauma

    Up to 60 days

  • Mortality at ICU discharge, 28 days, and hospital discharge

    Up to date of ICU discharge, 28 days, and hospital discharge

Other Outcomes (1)

  • The change in biomarker expression

    Baseline, 24 and 72 hours

Study Arms (2)

Control

ACTIVE COMPARATOR

Standard ventilation strategy.

Other: Standard Ventilation Strategy

Respiratory Mechanics

EXPERIMENTAL

The goal of this arm is to individualize tidal volume (VT) and PEEP according to respiratory mechanics.

Other: Respiratory Mechanics

Interventions

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.

Respiratory Mechanics

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.

Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (33)

New York University Grossman School of Medicine

New York, New York, 10016, United States

RECRUITING

Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)

Buenos Aires, Argentina

RECRUITING

Complejo Médico Policía Federal Argentina Churruca Visca

Buenos Aires, Argentina

RECRUITING

Hospital Británico de Buenos Aires

Buenos Aires, Argentina

RECRUITING

Sanatorio Anchorena Recoleta

Buenos Aires, Argentina

RECRUITING

Sanatorio Mater Dei

Buenos Aires, Argentina

RECRUITING

Sanatorio Anchorena San Martín

San Martín, Argentina

RECRUITING

St. Michael's Hospital

Toronto, Canada

RECRUITING

Toronto General Hospital

Toronto, Canada

RECRUITING

Toronto Western Hospital

Toronto, Canada

RECRUITING

Pontificia Universidad Católica de Chile

Santiago, Chile

RECRUITING

CHU Amiens-Picardie

Amiens, France

RECRUITING

Centre hospitalier universitaire d'Angers

Angers, France

RECRUITING

CH Victor Dupouy

Argenteuil, France

RECRUITING

CH de Beauvais

Beauvais, France

RECRUITING

CHU Bordeaux - Haut Leveque

Bordeaux, France

RECRUITING

Hopital de la Cavale Blanche - CHRU Brest

Brest, France

RECRUITING

CH de Cholet

Cholet, France

RECRUITING

Hopital Intercommunal de Creteil

Créteil, France

RECRUITING

CHU Grenoble-Alpes

Grenoble, France

RECRUITING

Hopital Roger Salengro - CHU Lille

Lille, France

RECRUITING

Groupe Hospitalier de la Region de Mulhouse et Sud Alsace

Mulhouse, France

RECRUITING

Hopital de l'Archet 1 - CHU de Nice

Nice, France

RECRUITING

Hopital Europeen Georges-Pompidou

Paris, France

RECRUITING

CHU de Poitiers - La Miletrie

Poitiers, France

RECRUITING

CH Bretagne Atlantique Vannes-Auray

Vannes, France

RECRUITING

HIA Robert Picque

Villenave-d'Ornon, France

RECRUITING

Arcispedale Sant'Anna

Ferrara, Italy

RECRUITING

University of Foggia

Foggia, Italy

RECRUITING

Policlinico Universitario Agostino Gemelli IRCCS

Rome, Italy

RECRUITING

OLVG

Amsterdam, North Holland, Netherlands

RECRUITING

L'Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

RECRUITING

Vall d'Hebron University Hospital

Barcelona, Spain

RECRUITING

Related Publications (2)

  • Coudroy R, Telias I, Jonkman A, Thille AW, Diehl JL, Peron N, Ko M, Bourion AA, Tiribelli N, Fredes S, Gutierrez M, Manchado Bruno A, Vasquez DN, Pratto RA, Plotnikow GA, Bianchini F, Accoce M, Dorado J, Spadaro S, La Rosa R, Prat G, Bailly P, Delbove A, Pacheco-Reyes A, Roca O, Kuteifan K, Rouze A, Grieco DL, Izura-Gomez M, Mancebo J, Sigaud F, Terzi N, Saccheri C, Dellamonica J, Richecoeur J, Setten M, Rauseo M, Beloncle F, Repusseau B, Roze H, Tran-Van D, Damiani F, Slama M, Kaufman DA, Maraffi T, Goligher EC, Plantefeve G, Determann R, Giamou M, Pham T, Del Sorbo L, Keown-Stoneman CDG, Nisenbaum R, Thorpe K, Piraino T, Chen L, Juni P, Ferguson ND, Slutsky AS, Brochard L; CAVIARDS study group. Careful ventilation in acute respiratory distress syndrome: the protocol of the CAVIARDS international multicentre randomised basket trial. BMJ Open. 2026 Feb 23;16(2):e115775. doi: 10.1136/bmjopen-2025-115775.

  • Villalba DS, Matesa A, Boni S, Gutierrez FJ, Moracci R, Plotnikow GA. Impact of High-Flow Nasal Cannula Oxygen Therapy on the Pressure of the Airway System in Humans. Respir Care. 2025 Jan;70(1):10-16. doi: 10.1089/respcare.12082.

Related Links

MeSH Terms

Conditions

Respiratory AspirationCOVID-19

Interventions

Respiratory Mechanics

Condition Hierarchy (Ancestors)

Respiration DisordersRespiratory Tract DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsPneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung Diseases

Intervention Hierarchy (Ancestors)

RespirationRespiratory Physiological PhenomenaCirculatory and Respiratory Physiological Phenomena

Study Officials

  • Laurent Brochard, MD

    Unity Health Toronto

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 6, 2019

First Posted

May 24, 2019

Study Start

November 23, 2020

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

September 1, 2026

Last Updated

January 16, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

The final anonymized trial dataset will be available on reasonable written request to the principal investigator one year after publication of the main manuscript.

Locations