RecruitingNCT03963622ClinicalTrials.gov record

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

ARDS

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THE QUICK READ

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type: Interventional
Phase: Not applicable
Age range: 18 years - Not specified
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 740 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.).

Read the full 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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

1. Age ≥ 18 y
2. 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:

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

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: Single masked

Control

Standard ventilation strategy.

Other: Standard Ventilation Strategy

Respiratory Mechanics

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

Other: Respiratory Mechanics

Respiratory Mechanics OTHER

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 OTHER

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.

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

All-cause 60-day mortality

Time frame: 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 measures

Duration of ventilation

Time frame: May exceed 60 days

Duration of ventilation in days

Duration of ICU and hospital stay

Time frame: May exceed 60 days

Duration of ICU and hospital stay in days

Number of patients with organ dysfunction

Time frame: Day 1-7, 14, 21, 28

Organ dysfunction as per the SOFA score

Number of patients with barotrauma

Time frame: Up to 60 days

Barotrauma defined as new onset of pneumothorax

Mortality at ICU discharge, 28 days, and hospital discharge

Time frame: Up to date of ICU discharge, 28 days, and hospital discharge

Mortality

Other measures

The change in biomarker expression

Time frame: Baseline, 24 and 72 hours

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

No results are flagged as posted.

Review the complete result tables and limitations in the official record.

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Research locations (33)

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Find a location in this study

33 locations

New York University Grossman School of MedicineNew York, New York, United StatesRecruiting

David Kaufman, MDCONTACT