Clinical trial NCT05024500: Clinical and Functional Outcomes of Critically Ill Patients With COVID-19
Official title: Clinical, Respiratory, Peripheral, Muscle and Functionality Outcomes of Adult ICU Inpatients and Rehabilitation-center Outpatients With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Respiratory Distress Syndrome (ARDS)
Lead sponsor: University of Pernambuco
Sponsor class: OTHER
Collaborators: name: Universidade Federal de Pernambuco
name: Coordination for the Improvement of Higher Education Personnel
name: Brazilian National Council for Scientific and Technological Development (CNPq)
name: Pernambuco Research Foundation (FACEPE)
First posted: 2021-08-27
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: three groups of treatments (A, B and C) are given so that one group receives only A while another group receives only B and the third group receives only C. All volunteers will be randomized to one of the three groups of treatment.
Primary purpose: TREATMENT

Brief summary: People affected by Severe Acute Respiratory Syndrome (SARS) by COVID-19 virus my require a long lasting invasive mechanical ventilation life support. To prevent damages to the lungs a number of protective lung ventilation measures are taken, one of them encounters the positive end expiratory pressure (PEEP) titration. Up to date, it is unclear the best method to titrate PEEP considering this unconventional syndrome compared to other etiologies. In addition to the long lasting advanced life support and bedridden condition, other factors may affect respiratory and peripheral muscle function of these patients. Therefore, the investigators intend to follow up these patients randomized to one of the three-arm experimental PEEP titration and after ICU discharge their status on clinical, laboratory and physical functions assessments.

Detailed description: Introduction: Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) requires mechanical ventilatory (MV) life support. In this scenario, lung protective strategies have been recommended for avoiding ventilator induced lung injuries mainly by inappropriate positive end expiratory pressure (PEEP) titration. However, the best method of PEEP titration for these patients remains unclear, since its clinical and morphofunctional phenotype may differ from the conventional acute respiratory distress syndrome (ARDS) phenotype resulted from other etiologies. In addition, these patients' condition of long lasting MV dependency and bed restriction may lead to deterioration of respiratory and peripheral muscles functions.

Objective: To compare the clinical and laboratory evolution and the respiratory and peripheral muscle functions in mechanically ventilated patients with COVID-19 submitted to PEEP titration by the following methods: ARDSNet protocol, driving pressure (DP) and electrical impedance tomography (EIT), as well as following them up after hospital discharge.

Methods: This is a controlled, randomized, double blind clinical trial with 90 mechanically ventilated patients to be randomized in one of the 3 PEEP titration- related groups: ARDSNet protocol, Driving Pressure-DP (electing PEEP level by the lowest DP) and by the EIT (PEEP selected will be the closest level above the intercept point of cumulated collapse and overdistension percentage curves). Clinical, laboratory, oxygenation, ventilation, respiratory and regional mechanics data, as well as peripheral muscle outcomes (strength and functionality) will be monitored from intubation to extubation in the supine and prone position. The outcomes of respiratory and peripheral muscles functionality will be monitored for six months after hospital discharge. All ethical principles will be respected with either written Free and Consent Term by the patient or relatives at the intensive care phase or at the post ICU discharge phase. Data will be registered for posterior analysis, which considers the difference between groups with p \<0.05.

Expected results: Based on this study, it is expected to identify the Peep titration method associated to the greater beneficial and less deleterious effects in critically ill patients on MV. Also to address appropriate lung protective ventilation strategy for these patients and to detect respiratory and peripheral muscle disorders as early as possible in critically ill survivors.

Eligibility criteria: Inclusion Criteria:

* mechanically ventilated patients due to acute respiratory failure associated to COVID-19 confirmed or suspected cases

Exclusion Criteria:

* consent refusal by patient, family or doctor

Primary outcomes:
measure: Murray Score (LIS)
timeFrame: 4 hours
measure: Potential lung recruitment measured during electrical impedance tomography
timeFrame: 4 hours
Secondary outcomes:
measure: Length of days in intensive care unit (ICU days)
timeFrame: Through study completion, an average of 1 year
measure: Work of breathing (WOB) measured during surface electromyography
timeFrame: 4 hours
measure: Duration of mechanical ventilation (MV days)
timeFrame: Through study completion, an average of 1 year
measure: ICU Mortality
timeFrame: Through study completion, an average of 1 year
measure: respiratory muscle strength
timeFrame: Through study completion, an average of 1 year
measure: Forced vital capacity (FVC) measured during spirometry
timeFrame: Through study completion, an average of 1 year
measure: diaphragmatic mobility measured during ultrasonography
timeFrame: Through study completion, an average of 1 year
measure: diaphragmatic thickening measured during ultrasonography
timeFrame: Through study completion, an average of 1 year
measure: breathing pattern measured during airway flowmeter
timeFrame: Through study completion, an average of 1 year
measure: peripheral muscle strength I
timeFrame: Through study completion, an average of 1 year
measure: peripheral muscle strength II
timeFrame: Through study completion, an average of 1 year
measure: peripheral muscle strength III
timeFrame: Through study completion, an average of 1 year
measure: six-minute walk test (6WT)
timeFrame: Through study completion, an average of 1 year
measure: functional capacity (Perme scale)
timeFrame: Through study completion, an average of 1 year
measure: daily activities performance
timeFrame: Through study completion, an average of 1 year
measure: quality of life measured by Short Form Health survey 36
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: Hospital das Clinicas - UFPE
state: Pernambuco
city: Recife
country: Brazil
facility: Physical Therapy Department, Universidade Federal de Pernambuco
state: Pernambuco
city: Recife
country: Brazil
facility: Hospital da Mulher do Recife
state: Pernambuco
city: Recife
country: Brazil
facility: Hospital Geral Otavio de Freitas
state: Pernambuco
Study officials:
affiliation: Universidade Federal de Pernambuco
name: Shirley Lima Campos, PhD
role: STUDY_DIRECTOR
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