Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19) (COVEN)

Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19) - COVEN Study

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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Distress Syndrome; SARS (Severe Acute Respiratory Syndrome); Mechanical Ventilation
• Intervention / Treatment: Other: ARDSNet; Other: EIT-Group

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.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eduardo LV Costa, PhD; Phone Number: +551130617361; Email: eduardoleitecosta@gmail.com
• Study Contact Backup: Name: Maria AM Nakamura, PhD; Phone Number: +551130617151; Email: mamiyukinakamura@gmail.com

Study Locations

• Brazil
  • São Paulo, Brazil, 05.403-010
    • Recruiting
    • USP Instituto do Coração
    • Contact: Eduardo LV Costa; Phone Number: +551130667361; Email: eduardoleitecosta@gmail.com
    • Contact: Maria AM Nakamura; Phone Number: +551130667151; Email: mamiyukinakamura@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: ARDSNet; ARDSNet protocol (low PEEP-FiO2 table). Ventilatory mode: volume-controlled ventilation Tidal volume (VT) will be adjusted to 4-6 mL/Kg of PBW and Plateau pressure < 30 cmH2O for the at least the first 12 hours after inclusion in the protocol pH should be maintained between 7.35-7.45 Oxygenation (SpO2) target ranges 90-95% Maximum respiratory rate = 35 breaths/min PEEP and FIO2 adjusted according to the low PEEP-FiO2 Table.	Other: ARDSNet; Low PEEP-FiO2 table ARDS Network ventilation protocol
EXPERIMENTAL: EIT-Group; The goal is to maintain driving pressure (DP) < 16 cmH2O. Ventilatory mode: pressure-controlled ventilation After a recruitment a maneuver, PEEP will be chosen according to a PEEP titration maneuver monitored with electrical impedance tomography Plateau pressure may exceed 30 cmH2O and VT may exceed 6 mL/Kg if DP < 16 cmH2O pH should be maintained between 7.15-7.40 Oxygenation (SpO2) target ranges 90 -95% Maximum respiratory rate = 50 bpm	Other: EIT-Group; A mechanical ventilation strategy with the main goal to maintain DP < 16 cmH2O

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average daily Modified Lung injury score until day 28	This score originally ranges from 0 to 4 points based on the average of 4 parameters (PaO2/FiO2, chest X-Ray, PEEP level, and Respiratory compliance). In the modified version, if the patient dies, he or she automatically receives a score of 5 irrespective of the other four parameters. If the patient is extubated, the score is automatically zero. We also substituted FiO2 for PEEP guaranteeing equivalence of the score when either the low or high PEEP-FiO2 table is applied.	daily

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High oxygen dependence free days until day 28	Number of days with less than or equal to 1 Liter/min of oxygen supplementation until day 28	28 days
Mechanical ventilation free days until day 28	Number of days free of mechanical ventilation assistance after protocol inclusion and before day 28	28 days
Incidence of shock or barotrauma	Occurrence of shock (persistent hypotension despite rescue measures) and incidence of barotrauma	28 days
Incidence of acute renal failure requiring renal replacement therapy	Occurrence of acute renal failure that justifies renal replacement therapy	28 days
28-day mortality	Percentage of patients who died in each arm up to 28 days	28 days

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: InCor Heart Institute
• Investigators: Principal Investigator: Eduardo LV Costa, PhD, Hospital das Clinicas from University of São Paulo

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2020
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (ACTUAL): August 4, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: CAAE: 30938720800000068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No