Effects of IMT on Functional Capacity in Patients With Chronic COVID After Hospital Discharge (InsCOVID)

Effects of Inspiratory Muscle Training on Maximal Functional Capacity in Patients With Chronic COVID After Hospital Discharge

Exercise intolerance and fatigue are the most common symptoms in patients with chronic COVID after hospital discharge. Muscle deconditioning, dysautonomia, and exercise hyperventilation have been proposed as potential mechanisms contributing to exercise functional capacity limitation in Long-COVID. Along this line, combined exercise training or inspiratory muscle training (IMT) alone have already been demonstrated to be feasible therapeutic options for Long-COVID patients. However, we do not have evidence about the effects of a home-based IMT program for 12-week on peak oxygen consumption (peakVO2). in patients chronic COVID (>3 months) after hospital discharge.

This is a prospective study, blinded for the evaluator, randomized (1:1) to receive standard management alone or combined with a program of IMT that will be carried out in a single center. After randomization, patients will be clinically evaluated. The primary endpoint (peakVO2) will be assessed by cardiopulmonary exercise testing (CPET) at 12-week. Patients with chronic COVID (>3 months) after hospital discharge will be enrolled. A sample size estimation [alfa: 0.05, power: 80%, a 15% loss rate, and at least a delta change of mean peakVO2: +3 mL/kg/min (SD±2.5)] of 26 patients (13 per arm) would be necessary to test our hypothesis.

Study Overview

• Status: Completed
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Behavioral: Inspiratory muscle training

Detailed Description

Exercise intolerance and fatigue are the most common symptoms in patients with chronic COVID after hospital discharge. Muscle deconditioning, dysautonomia, and exercise hyperventilation have been proposed as potential mechanisms contributing to exercise functional capacity limitation in Long-COVID. Along this line, combined exercise training or inspiratory muscle training (IMT) alone have already been demonstrated to be feasible therapeutic options for Long-COVID patients. However, we do not have evidence about the effects of a home-based IMT program for 12-week on peak oxygen consumption (peakVO2). in patients chronic COVID (>3 months) after hospital discharge.

This is a prospective study, blinded for the evaluator, randomized (1:1) to receive standard management alone or combined with a program of IMT that will be carried out in a single center. Patients allocated to the IMT arm will be instructed to train at home twice daily, for 20 minutes each session, using a Threshold inspiratory muscle trainer (Respironics Inc., Parsippany, NJ). They will be instructed by a physiotherapist responsible for training intervention and educated to maintain diaphragmatic breathing during the training period. The subjects will start breathing at a resistance equal to 25% to 30% of their maximal inspiratory mouth pressure (MIP) for 1 week. The respiratory therapist will examine the patients at weekly intervals by checking the diary card and measuring the MIP each time. The resistance will be modified each session according to the 25% to 30% of their MIP measured. After randomization, patients will be clinically evaluated. The primary endpoint (peakVO2) will be assessed by cardiopulmonary exercise testing (CPET) at 12-week. Patients with chronic COVID (>3 months) after hospital discharge will be enrolled. A sample size estimation [alfa: 0.05, power: 80%, a 15% loss rate, and at least a delta change of mean peakVO2: +3 mL/kg/min (SD±2.5)] of 26 patients (13 per arm) would be necessary to test our hypothesis.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46010
    • INCLIVA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Symptomatic adult patients >18 years old with the previous admission due to SARS-CoV-2 pneumonia
2. > 3-month after discharge
3. The patient provides informed consent

Exclusion Criteria:

1. Inability to perform a maximal baseline exercise test
2. Structural heart disease, valve heart disease, or diastolic dysfunction estimated by 2-dimensional echocardiography
3. Patients with previous ischemic heart disease, heart failure, myocardiopathy, or myocarditis
4. Effort angina or signs of ischemia during CPET
5. Significant primary pulmonary disease, including a history of pulmonary arterial hypertension, chronic thromboembolic pulmonary disease, or chronic obstructive pulmonary disease

(g) Treatment with digitalis, calcium channel blockers, β-blocker or ivabradine (h) Patients with chronic kidney disease (glomerular filtration rate <60mL/min/1.73m2) (i) Patients with pacemakers or previous history of atrial fibrillation; (j) patients with autoimmune, inflammatory or active neoplastic disease k) Anemia (l) Pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control arm; Patients allocated to the control arm will not receive inspiratory muscle training. They will be checked each week by a physiotherapist responsible for training intervention who will measure their maximal inspiratory pressure
Active Comparator: Inspiratory muscle training; Patients allocated to the IMT arm will be instructed to train at home twice daily, for 20 minutes each session, using a Threshold inspiratory muscle trainer (Respironics Inc., Parsippany, NJ). They will be instructed by a physiotherapist responsible for training intervention and educated to maintain diaphragmatic breathing during the training period. The subjects will start breathing at a resistance equal to 25% to 30% of their maximal inspiratory mouth pressure (MIP) for 1 week. The respiratory therapist will examine the patients at weekly intervals by checking the diary card and measuring the MIP each time. The resistance will be modified each session according to the 25% to 30% of their MIP measured.	Behavioral: Inspiratory muscle training; Patients allocated to the IMT arm will be instructed to train at home twice daily, for 20 minutes each session, using a Threshold inspiratory muscle trainer (Respironics Inc., Parsippany, NJ). They will be instructed by a physiotherapist responsible for training intervention and educated to maintain diaphragmatic breathing during the training period. The subjects will start breathing at a resistance equal to 25% to 30% of their maximal inspiratory mouth pressure (MIP) for 1 week. The respiratory therapist will examine the patients at weekly intervals by checking the diary card and measuring the MIP each time. The resistance will be modified each session according to the 25% to 30% of their MIP measured.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak oxygen consumption	Maximal functional capacity will be evaluated with incremental and symptom-limited cardiopulmonary exercise testing. Peak oxygen consumption (peakVO2) will be considered the highest value of VO2 during the last 20 seconds of exercise.	12-week

Collaborators and Investigators

• Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
• Investigators: Principal Investigator: Patricia Palau, MD, PhD, INCLIVA-Hospital Clínico Universitario

Publications and helpful links

General Publications

• Palau P, Dominguez E, Lopez L, Heredia R, Gonzalez J, Ramon JM, Serra P, Santas E, Bodi V, Sanchis J, Chorro FJ, Nunez J. Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: Rationale and Study Design of a Prospective Randomized Controlled Trial. Clin Cardiol. 2016 Aug;39(8):433-9. doi: 10.1002/clc.22555. Epub 2016 Aug 2.
• Palau P, Dominguez E, Nunez E, Schmid JP, Vergara P, Ramon JM, Mascarell B, Sanchis J, Chorro FJ, Nunez J. Effects of inspiratory muscle training in patients with heart failure with preserved ejection fraction. Eur J Prev Cardiol. 2014 Dec;21(12):1465-73. doi: 10.1177/2047487313498832. Epub 2013 Jul 17.
• Palau P, Dominguez E, Sastre C, Martinez ML, Gonzalez C, Bondia E, Albiach C, Nunez J, Lopez L. Effect of a home-based inspiratory muscular training programme on functional capacity in patients with chronic COVID-19 after a hospital discharge: protocol for a randomised control trial (InsCOVID trial). BMJ Open Respir Res. 2022 Jul;9(1):e001255. doi: 10.1136/bmjresp-2022-001255.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2022
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: March 12, 2022
• First Submitted That Met QC Criteria: March 12, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: 2021/226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Yes: There is a plan to make IPD and related data dictionaries available
• IPD Sharing Time Frame: Starting 3 months after publication
• IPD Sharing Access Criteria: Data is available upon the reasonable request
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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