Inspiratory Muscle Training in COVID-19 Patients (ADDIMTCOVID)

Adjunctive Inspiratory Muscle Training for Patients With COVID-19

This study aims to investigate whether adjunctive inspiratory muscle training (IMT) can enhance the benefits of pulmonary rehabilitation (PR) in patients with COVID-19. 120 patients will be randomized into an interventional group (PR plus IMT) and a control group (sham IMT plus PR). Improvement in quality of life, peak VO2 and VE/VCO2 slope will be defined as a primary outcome. Maximal inspiratory pressure, inspiratory muscle endurance, pulmonary function testing, severity of fatigue, cost-effectiveness and six minute walk test will be defined as the secondary outcomes.

Study Overview

• Status: Completed
• Conditions: Covid19; Exercise
• Intervention / Treatment: Device: inspiratory muscle traiing

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • DF
    • Brasilia, DF, Brazil, 700000
      • Secretaria de Saúde do Distrito Federal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

To be eligible, participants must be:

• over 18 years of age
• confirmed COVID-19 diagnosis
• Individuals that required hospitalization and either i) non-invasive respiratory support (CPAP, high-flow oxygen catheter, non-breathing oxygen mask, or ii) invasive mechanical ventilation within three months of study recruitment.

Exclusion Criteria:

• Pregnancy
• Dependence on others to perform activities of daily living during the month prior to the current ICU admission (gait aids are acceptable)
• documented cognitive impairment
• Proven or suspected spinal cord injury, or other neuromuscular diseases that will result in a permanent or prolonged weakness (not including ICU acquired weakness)
• Severe neurological disease
• Death is deemed inevitable as a result of the current illness and either the patient or treating clinical or substitute decision-maker are not committed to full active treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; The training volume will be 24 sessions. Training frequency will be 3 sessions per week. Duration of training sessions will be around 60min. Patients will perform endurance training or interval training at moderate to high intensities. IMT in both groups will be performed using the PowerBreathe KHP2 device (POWERbreatheKHP2, HaB, International, Southam, UK). Training intensity in the intervention group will be set initially at a load of 50% of patients' maximal inspiratory mouth pressure (MIP). This initial load will be continuously and gradually increased to the highest tolerable intensity during each of the supervised sessions.	Device: inspiratory muscle traiing; The patients are encouraged to inhale against a load to increase the inspiratory muscle strength and endurance; Other Names: tapered flow resistive loading
Active Comparator: Control group; The training volume will be 24 sessions. Training frequency will be 3 sessions per week. Duration of training sessions will be around 60min. Patients will perform endurance training or interval training at moderate to high intensities. Sham IMT will be performed using the PowerBreathe KHP2 device (POWERbreatheKHP2, HaB, International, Southam, UK). Training intensity in the control group will be set at 10% baseline PImax and will be not modified throughout the intervention period.	Device: inspiratory muscle traiing; The patients are encouraged to inhale against a load to increase the inspiratory muscle strength and endurance; Other Names: tapered flow resistive loading

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiopulmonary Exercise Testing Measurements	Peak VO2 is a measurement of oxygen consumption rate during exercise (milliliters of oxygen per minute). It is calculated by continuous measurement of oxygen consumed during exercise while patients breath through a mask/tube. To account for variability in patient size, the oxygen consumption is divided by patient body weight.The VE/VCO2 slope is calculated as the ratio of minute ventilation (VE) and carbon dioxide production (VCO2). Because these measurements share the same units, the resultant ratio is unitless.The ventilatory anaerobic threshold (VAT) will be determined by the V-slope method.	change from baseline in Peak VO2, VE/VCO2 slope and VAT at 8 weeks and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
severity of fatigue	Fatigue severity scale (FSS) is a questionnaire consisting of 9 questions showing the degree of fatigue of patients. An average score of less than 2.8 indicates no fatigue, and more than 6.1 indicates chronic fatigue syndrome	change from baseline in FSS score at 8 weeks and 6 months
Anxiety and Depression	Hospital anxiety and depression scale (HADS) is a 14-item questionnaire for screening anxiety (7 items) and depression (7 items). Each item is scored from 0-3 (a 4-point severity scale). Highest anxiety or depression score is 21. Patients are defined as having anxiety or depression or both if the score is 8 or more in the each subscale.	Change from baseline in HADS score at 8 weeks and 6 months
incremental cost-utility ratio	Utility will be measured by Quality Adjusted Life Year (QALYs) as estimated from responses to the Euroqol-5 Dimensions (EQ-5D 5L) health-related quality of life questionnaire. The questionnaire focuses on 5 dimensions: mobility, personal autonomy, current activities, pain/discomfort and anxiety/depression. For each of these dimensions, 5 answers are possible.	6 months
Health- related quality of life	EQ-5D is a standardized tool for the assessment of quality of life in 5 different dimensions (Mobility, Self-Care, Usual Activities, Pain/Discomfort, Anxiety/Depression). Possible scores range from 1 (No problem) to 3 (Extreme problems) and each dimension are evaluated individually	change from baseline in EQ-5D score at 8 weeks and 6 months
Pulmonary function testing	Spirometry will be performed with a spirometer (Microlab 3.500; CareFusion, Yorba Linda, CA, USA). Three forced expiration maneuvers will be performed for validity and reproducibility purposes according to ATS/ERS criteria, with patients sitting, in a room with controlled temperature, ambient pressure, and relative humidity. The following variables will be analyzed: (a) forced vital capacity (FVC, L), (b) forced expiratory volume in the first second (FEV1, L).	change from baseline in FEV1 and FVC in Liters at 8 weeks and 6 months.
Dyspnea	The modified Medical Research Council Dyspnea Scale (mMRC). A score from 0-4 is used to classify the impact of dyspnea on physical function in patients with respiratory limitations. 0 represents a person who suffers from dyspnea only with strenuous exercise. 4 represents a person who are to breathless to leave the house, or breathless when dressing/undressing.	change from baseline in mMRC score at 8 weeks and 6 months
Respiratory muscle strength	Pulmonary function test with Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) measurements	change from baseline in MIP and MEP at 8 weeks and 6 months
Postural Control	postural control assessed by stabilometry test	change from baseline in Postural stability test and fall risk test at 8 weeks
isometric knee extension strength	peripheral muscle stregnth assessed by isometric load dynamometer	change from baseline in Nm at 8 weeks
displacement	outcomes assessed by baropodometry	change from baseline in CM2 at 8 weeks
trajectory	outcome assessed by baropodometry	change from baseline in CM2 at 8 weeks
isometric knee flexion strength	peripheral muscle stregnth assessed by isometric load dynamometer	change from baseline in Nm at 8 weeks
dynamic balance	dynamic balance assessed by Mini-BEST testing	change from baseline in Total score at 8 weeks
Sit to Stand Test	exercise capacity assessed by Sit to Stand test	change from baseline in repetitions at 8 weeks

Collaborators and Investigators

• Sponsor: Escola Superior de Ciencias da Saude
• Collaborators: University of Brasilia; JBS/CNPq

Publications and helpful links

General Publications

• Maldaner V, Coutinho J, Santana ANDC, Cipriano GFB, Oliveira MC, Carrijo MM, Lino MEM, Cahalin LP, Lima AG, Borges R, Santos DB, Silva IO, Oliveira LVF, Cipriano G Jr. Adjunctive inspiratory muscle training for patients with COVID-19 (COVIDIMT): protocol for randomised controlled double-blind trial. BMJ Open. 2021 Sep 22;11(9):e049545. doi: 10.1136/bmjopen-2021-049545.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: inspiratory muscle training; respiratory function tests
• 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; COVID-19; Respiratory Aspiration
• Other Study ID Numbers: CNPQ092020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No