급성호흡곤란증후군(COVID-19 및 Non-COVID-19)의 주의 깊은 환기 (CAVIARDS)
급성 호흡곤란 증후군의 주의 깊은 환기
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.).
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Laurent Brochard, MD
- 전화번호: 5686 416-864-6060
- 이메일: laurent.brochard@unityhealth.to
연구 장소
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North Holland
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Amsterdam, North Holland, 네덜란드
- 모병
- OLVG
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연락하다:
- Rogier Determann, MD
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New York
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New York, New York, 미국, 10016
- 모병
- New York University Grossman School of Medicine
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연락하다:
- David Kaufman, MD
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Barcelona, 스페인
- 모병
- Vall d'Hebron University Hospital
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연락하다:
- Andres F Pacheco, MD
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Barcelona, 스페인
- 모병
- L'Hospital de la Santa Creu i Sant Pau
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연락하다:
- Marta I Gomez, MD
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Buenos Aires, 아르헨티나
- 모병
- Hospital Británico de Buenos Aires
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연락하다:
- Gustavo Plotnikov, RRT
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Buenos Aires, 아르헨티나
- 모병
- Complejo Médico Policía Federal Argentina Churruca Visca
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연락하다:
- Maria Guaymas, MD
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Buenos Aires, 아르헨티나
- 모병
- Sanatorio Anchorena Recoleta
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연락하다:
- Daniela Vasquez, MD
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Buenos Aires, 아르헨티나
- 모병
- Sanatorio Mater Dei
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연락하다:
- Magalí Gutiérrez, MD
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Buenos Aires, 아르헨티나
- 모병
- Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)
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연락하다:
- Pablo Rodriguez, MD
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San Martin, 아르헨티나
- 모병
- Sanatorio Anchorena San Martín
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연락하다:
- Matias Accoce, RRT
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Ferrara, 이탈리아
- 모병
- Arcispedale Sant'Anna
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연락하다:
- Savino Spadaro, MD
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Foggia, 이탈리아
- 모병
- University of Foggia
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연락하다:
- Michela Rauseo, MD
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Rome, 이탈리아
- 모병
- Policlinico Universitario Agostino Gemelli IRCCS
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연락하다:
- Domenico L Grieco, MD
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Santiago, 칠레
- 모병
- Pontificia Universidad Católica de Chile
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연락하다:
- Felipe Damiani, PhD
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Toronto, 캐나다
- 모병
- St. Michael's Hospital
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연락하다:
- Laurent Brochard, MD
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Toronto, 캐나다
- 모병
- Toronto General Hospital
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연락하다:
- Ewan Goligher, MD
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Toronto, 캐나다
- 모병
- Toronto Western Hospital
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연락하다:
- Irene Telias, MD
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Amiens, 프랑스
- 모병
- CHU Amiens-Picardie
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연락하다:
- Michel Slama, MD
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Angers, 프랑스
- 모병
- Centre hospitalier universitaire d'Angers
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연락하다:
- Francois Beloncle, MD
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Argenteuil, 프랑스
- 모병
- CH Victor Dupouy
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연락하다:
- Gaetan Plantefeve, MD
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Beauvais, 프랑스
- 모병
- CH de Beauvais
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연락하다:
- Jack Richecoeur, MD
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Bordeaux, 프랑스
- 모병
- CHU Bordeaux - Haut Leveque
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연락하다:
- Benjamin Repusseau, MD
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Brest, 프랑스
- 모병
- Hopital de la Cavale Blanche - CHRU Brest
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연락하다:
- Gwenael Prat, MD
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Cholet, 프랑스
- 모병
- CH de Cholet
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연락하다:
- Johann Auchabie, MD
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Créteil, 프랑스
- 모병
- Hopital Intercommunal de Creteil
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연락하다:
- Tommaso Maraffi, MD
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Grenoble, 프랑스
- 모병
- CHU Grenoble-Alpes
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연락하다:
- Florian Sigaud, MD
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Lille, 프랑스
- 모병
- Hopital Roger Salengro - CHU Lille
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연락하다:
- Saad Nseir, MD
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Mulhouse, 프랑스
- 모병
- Groupe Hospitalier de la Region de Mulhouse et Sud Alsace
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연락하다:
- Khaldoun Kuteifan, MD
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Nice, 프랑스
- 모병
- Hopital de l'Archet 1 - CHU de Nice
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연락하다:
- Jean Dellamonica, MD
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Paris, 프랑스
- 모병
- Hopital Europeen Georges-Pompidou
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연락하다:
- Jean-Luc Diehl, MD
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Poitiers, 프랑스
- 모병
- CHU de Poitiers - La Miletrie
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연락하다:
- Remi Coudroy, MD
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Vannes, 프랑스
- 모병
- CH Bretagne Atlantique Vannes-Auray
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연락하다:
- Agathe Delbove, MD
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Villenave-d'Ornon, 프랑스
- 모병
- HIA Robert Picque
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연락하다:
- David Tran-Van, MD
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Control
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. |
|
실험적: Respiratory Mechanics
The goal of this arm is to individualize tidal volume (VT) and PEEP according to 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. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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All-cause 60-day mortality
기간: 60 days
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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
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Duration of ventilation
기간: May exceed 60 days
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Duration of ventilation in days |
May exceed 60 days
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Duration of ICU and hospital stay
기간: May exceed 60 days
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Duration of ICU and hospital stay in days |
May exceed 60 days
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Number of patients with organ dysfunction
기간: Day 1-7, 14, 21, 28
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Organ dysfunction as per the SOFA score |
Day 1-7, 14, 21, 28
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Number of patients with barotrauma
기간: Up to 60 days
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Barotrauma defined as new onset of pneumothorax |
Up to 60 days
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Mortality at ICU discharge, 28 days, and hospital discharge
기간: Up to date of ICU discharge, 28 days, and hospital discharge
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Mortality |
Up to date of ICU discharge, 28 days, and hospital discharge
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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The change in biomarker expression
기간: Baseline, 24 and 72 hours
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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
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공동 작업자 및 조사자
협력자
수사관
- 수석 연구원: Laurent Brochard, MD, Unity Health Toronto
간행물 및 유용한 링크
일반 간행물
- 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.
- 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.
유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 1765
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
The final anonymized trial dataset will be available on reasonable written request to the principal investigator one year after publication of the main manuscript.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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