Clinical trial NCT04497454: Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19)
Official title: Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19) - COVEN Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Respiratory Distress Syndrome
Mechanical Ventilation
SARS (Severe Acute Respiratory Syndrome)
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: InCor Heart Institute
First posted: 2020-08-04
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, single-center, open-label, superiority, controlled trial
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized, single-center, open-label controlled trial, designed to compare the efficacy of two ventilation strategies (Low Tidal Volume and positive end-expiratory pressure (PEEP) based on the Acute Respiratory Distress Syndrome (ARDS) Network low PEEP-fraction of inspired oxygen inspired oxygen fraction (FIO2) Table versus Low Driving Pressure and PEEP guided by Electrical Impedance Tomography (EIT) in reducing daily lung injury score in patients with acute respiratory distress syndrome caused by COVID-19. The two strategies incorporate different prioritizations of clinical variables. The PEEP-FIO2 table strategy aims to reduce lung overdistension, even if it requires tolerating worse gas exchange. EIT-guided strategy prioritizes mechanical stress protection, avoiding alveolar overdistension and collapse.

Detailed description: Mechanical ventilatory strategy of the ARDS Network low PEEP-FiO2 table will be followed in the control arm. This strategy consists of at least 12 hours of controlled mechanical ventilation following prespecified PEEP and FiO2 combinations chosen dynamically targeting oxygenation. Tidal volume is set at 4-6 mL/Kg of predicted body weight (PBW) and plateau pressure is kept below 30 centimeters of water (cmH2O). Respiratory rate can be as high as 35 breaths per minute titrated to a potential of hydrogen (pH) 7.30-7.45. As oxygenation improves, patients are transitioned to assisted ventilation and then to pressure support ventilation until they are ready to be liberated from the ventilator. During this phase, no attempt is made to control plateau pressures or tidal volumes. In the intervention arm, minimizing tidal lung strain by keeping driving pressure below 16 cmH2O throughout the mechanical ventilation period will be targeted. The controlled phase will last at least 48 hours. PEEP will be selected according to a PEEP titration maneuver with EIT at the start of the intervention. This PEEP level will be kept until extubation. Respiratory rate can be as high as 50 breaths per minute targeting a pH of 7.15-7.45.

Eligibility criteria: Inclusion Criteria:

Patients under mechanical ventilation with ARDS (Berlin definition) caused by SARS-COV2 infection:

* ARDS diagnosis in less than 24 hours
* Respiratory System Compliance of 0.6 mL/cmH2O/Kg of PBW

Exclusion Criteria:

* Age \< 18 years
* Active bronchopleural fistula
* History of chronic and disabling respirator disease, requiring home oxygen treatment
* Chronic pulmonary arterial hypertension (pulmonary artery systolic pressure \> 40 mmHg)
* Huge intrathoracic tumoral mass
* Electrical impedance tomography monitoring contraindications (as thoracic wounds or burns, electronic implantable devices)
* Hemodynamic instability (systolic pressure \< 80 mmHg or mean arterial pressure \< 60 mmHg, despite vasopressor drugs; and/or heart rate \< 55bpm) - this patient may be included after recovered from hemodynamic instability
* Not drained pneumothorax or subcutaneous emphysema or bronchopleural fistula
* Patients at risk of intracranial hypertension development or post Cardiopulmonary resuscitation (first 72 hours)
* Pregnancy
* Impossibility of monitoring with EIT
* Not committed to full support or life expectation \< 24 hours
* Legal responsible or clinical team refusal to participate in the study.

Primary outcomes:
measure: Average daily Modified Lung injury score until day 28
timeFrame: daily
Secondary outcomes:
measure: High oxygen dependence free days until day 28
timeFrame: 28 days
measure: Mechanical ventilation free days until day 28
timeFrame: 28 days
measure: Incidence of shock or barotrauma
timeFrame: 28 days
measure: Incidence of acute renal failure requiring renal replacement therapy
timeFrame: 28 days
measure: 28-day mortality
timeFrame: 28 days
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: USP Instituto do Coração
Study officials:
affiliation: Hospital das Clinicas from University of São Paulo
name: Eduardo LV Costa, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hohmann F, Wedekind L, Grundeis F, Dickel S, Frank J, Golinski M, Griesel M, Grimm C, Herchenhahn C, Kramer A, Metzendorf MI, Moerer O, Olbrich N, Thieme V, Vieler A, Fichtner F, Burns J, Laudi S. Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19. Cochrane Database Syst Rev. 2022 Jun 29;6(6):CD015077. doi: 10.1002/14651858.CD015077.