Clinical and Functional Outcomes of Critically Ill Patients With COVID-19

Acute Respiratory Distress Syndrome (ARDS) Clinical Trial

— COVIDPTcare  

Official title:

Clinical, Respiratory, Peripheral, Muscle and Functionality Outcomes of Adult ICU Inpatients and Rehabilitation-center Outpatients With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05024500
• Other study ID #: COVIDPTcare
• Status: Completed
• Phase: N/A
• Start date: October 21, 2020
• Est. completion date: December 30, 2022

Study information

• Verified date: March 2023
• Source: University of Pernambuco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 30, 2022
• Est. primary completion date: July 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome (ARDS)
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Other:
• ARDSNet table
The setting of the lowest PEEP level and FiO2 match stated by the table to achieve a goal oxygenation.
• Driving Pressure
The setting of the lowest PEEP level by the lowest correspondent driving pressure, which is defined by the difference of plateau pressure, after a modified alveolar recruitment maneuver.
• Electrical Impedance Tomography
The setting of the PEEP level above the intersection of the curves representing relative alveolar overdistention and collapse, after a modified alveolar recruitment maneuver.

Locations

Country	Name	City	State
Brazil	Hospital da Mulher do Recife	Recife	Pernambuco
Brazil	Hospital das Clinicas - UFPE	Recife	Pernambuco
Brazil	Hospital Geral Otavio de Freitas	Recife	Pernambuco
Brazil	Physical Therapy Department, Universidade Federal de Pernambuco	Recife	Pernambuco

Sponsors (5)

Lead Sponsor	Collaborator
University of Pernambuco	Brazilian National Council for Scientific and Technological Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES), Pernambuco Research Foundation (FACEPE), Universidade Federal de Pernambuco

Country where clinical trial is conducted

Brazil, 

References & Publications (15)

Adhikari SP, Meng S, Wu YJ, Mao YP, Ye RX, Wang QZ, Sun C, Sylvia S, Rozelle S, Raat H, Zhou H. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Dis Poverty. 2020 Mar 17;9(1):29. doi: 10.1186/s40249-020-00646-x. — View Citation

Adler A, Arnold JH, Bayford R, Borsic A, Brown B, Dixon P, Faes TJ, Frerichs I, Gagnon H, Garber Y, Grychtol B, Hahn G, Lionheart WR, Malik A, Patterson RP, Stocks J, Tizzard A, Weiler N, Wolf GK. GREIT: a unified approach to 2D linear EIT reconstruction of lung images. Physiol Meas. 2009 Jun;30(6):S35-55. doi: 10.1088/0967-3334/30/6/S03. Epub 2009 Jun 2. — View Citation

Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019.0555. — View Citation

Costa EL, Borges JB, Melo A, Suarez-Sipmann F, Toufen C Jr, Bohm SH, Amato MB. Bedside estimation of recruitable alveolar collapse and hyperdistension by electrical impedance tomography. Intensive Care Med. 2009 Jun;35(6):1132-7. doi: 10.1007/s00134-009-1447-y. Epub 2009 Mar 3. — View Citation

Frerichs I, Becher T, Weiler N. Electrical impedance tomography imaging of the cardiopulmonary system. Curr Opin Crit Care. 2014 Jun;20(3):323-32. doi: 10.1097/MCC.0000000000000088. — View Citation

Fumagalli J, Berra L. What does the Acute Respiratory Distress Syndrome trial (ART) teach us?-it is time for precision medicine and precision trials in critical care! J Thorac Dis. 2018 Mar;10(3):1300-1303. doi: 10.21037/jtd.2018.03.31. No abstract available. — View Citation

Goh KJ, Choong MC, Cheong EH, Kalimuddin S, Duu Wen S, Phua GC, Chan KS, Haja Mohideen S. Rapid Progression to Acute Respiratory Distress Syndrome: Review of Current Understanding of Critical Illness from Coronavirus Disease 2019 (COVID-19) Infection. Ann Acad Med Singap. 2020 Mar 16;49(3):108-118. — View Citation

Huh JW, Jung H, Choi HS, Hong SB, Lim CM, Koh Y. Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome. Crit Care. 2009;13(1):R22. doi: 10.1186/cc7725. Epub 2009 Feb 24. — View Citation

Liu S, Tan L, Moller K, Frerichs I, Yu T, Liu L, Huang Y, Guo F, Xu J, Yang Y, Qiu H, Zhao Z. Identification of regional overdistension, recruitment and cyclic alveolar collapse with electrical impedance tomography in an experimental ARDS model. Crit Care. 2016 May 3;20(1):119. doi: 10.1186/s13054-016-1300-y. — View Citation

Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988 Sep;138(3):720-3. doi: 10.1164/ajrccm/138.3.720. No abstract available. Erratum In: Am Rev Respir Dis 1989 Apr;139(4):1065. — View Citation

Sahetya SK, Hager DN, Stephens RS, Needham DM, Brower RG. PEEP Titration to Minimize Driving Pressure in Subjects With ARDS: A Prospective Physiological Study. Respir Care. 2020 May;65(5):583-589. doi: 10.4187/respcare.07102. Epub 2019 Nov 26. — View Citation

Silveira LTYD, Silva JMD, Tanaka C, Fu C. Decline in functional status after intensive care unit discharge is associated with ICU readmission: a prospective cohort study. Physiotherapy. 2019 Sep;105(3):321-327. doi: 10.1016/j.physio.2018.07.010. Epub 2018 Aug 2. — View Citation

Thomas P, Baldwin C, Bissett B, Boden I, Gosselink R, Granger CL, Hodgson C, Jones AY, Kho ME, Moses R, Ntoumenopoulos G, Parry SM, Patman S, van der Lee L. Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations. J Physiother. 2020 Apr;66(2):73-82. doi: 10.1016/j.jphys.2020.03.011. Epub 2020 Mar 30. — View Citation

Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-260. doi: 10.1038/s41569-020-0360-5. — View Citation

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Murray Score (LIS)	Scoring system for lung injury including hypoxemia, respiratory system compliance, chest radiographic findings and level of PEEP. The minimum value is zero and the maximum value is sixteen. The higher the score the worse outcome.	4 hours
Primary	Potential lung recruitment measured during electrical impedance tomography	to quantify lung ventilation distribution	4 hours
Secondary	Length of days in intensive care unit (ICU days)	to quantify the number of days spent in a critical care unit	Through study completion, an average of 1 year
Secondary	Work of breathing (WOB) measured during surface electromyography	measured in root-mean-squared electromyography signals	4 hours
Secondary	Duration of mechanical ventilation (MV days)	to quantity the number of days with use of invasive mechanical ventilation in inpatients.	Through study completion, an average of 1 year
Secondary	ICU Mortality	to quantify number of living days between ICU admission and deceased status	Through study completion, an average of 1 year
Secondary	respiratory muscle strength	maximal static respiratory mouth pressures	Through study completion, an average of 1 year
Secondary	Forced vital capacity (FVC) measured during spirometry	measures obtained by spirometry in outpatients	Through study completion, an average of 1 year
Secondary	diaphragmatic mobility measured during ultrasonography	diaphragmatic excursion expressed in millimeters	Through study completion, an average of 1 year
Secondary	diaphragmatic thickening measured during ultrasonography	diaphragmatic thickening expressed in millimeters	Through study completion, an average of 1 year
Secondary	breathing pattern measured during airway flowmeter	a device to quantify airway flow	Through study completion, an average of 1 year
Secondary	peripheral muscle strength I	to be evaluated by Medical Research Council's scale. The minimum score is 0 and the maximum is 60. The higher the score, the better outcome.	Through study completion, an average of 1 year
Secondary	peripheral muscle strength II	to be evaluated by a handgrip dynamometers in outpatients	Through study completion, an average of 1 year
Secondary	peripheral muscle strength III	to be evaluated by a handheld dynamometer in outpatients	Through study completion, an average of 1 year
Secondary	six-minute walk test (6WT)	sub-maximal exercise test used to assess aerobic capacity and endurance in outpatients	Through study completion, an average of 1 year
Secondary	functional capacity (Perme scale)	The minimum score is 0 and the maximum is 32. The higher the score, the better outcome.	Through study completion, an average of 1 year
Secondary	daily activities performance	to be evaluated by Barthel Index in outpatients	Through study completion, an average of 1 year
Secondary	quality of life measured by Short Form Health survey 36	score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	Through study completion, an average of 1 year