Respiratory Muscles After Hospitalisation for COVID-19

Covid19 Clinical Trial

— REMAP-COVID-19  

Official title:

Respiratory Muscle Function After Hospitalisation for COVID-19 -Pathophysiological Model on Severity, Determinants and Clinical Consequences of Respiratory Muscle Strength Impairment in Patients Who Had Been Hospitalised for COVID-19-

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04854863
• Other study ID #: CTCA 20-515
• Status: Completed
• Start date: June 1, 2021
• Est. completion date: November 20, 2023

Study information

• Verified date: November 2023
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Fatigue and exercise intolerance after survived COVID-19-infection might be related to weakness of the respiratory muscles especially following invasive mechanical ventilation in the Intensive Care Unit. The aim of the project is to measure respiratory muscle function and strength in our respiratory physiology laboratory (Respiratory Physiology Laboratory, Department of Pneumology and Intensive Care Medicine, Head: Professor Michael Dreher) in patients who survived a severe COVID-19-infection (25 with a severe course requiring mechanical ventilation in the intensive care unit, 25 with a moderate-severe course requiring administration of supplemental oxygen only, respectively). Based on this data the aim is to develop a model which determines the severity, pathophysiology and clinical consequences of respiratory muscle dysfunction in patients who had been hospitalised for COVID-19. This will potentially prove the importance of a dedicated pulmonologic rehabilitation with respiratory muscle strength training in patients who had been hospitalised for COVID-19.

Description:

The aim of the present project is to comprehensively measure respiratory muscle function and strength in patients who survived a hospitalisation for a severe COVID-19-infection (25 with a severe course requiring mechanical ventilation in the intensive care unit, 25 with a moderate-severe course requiring administration of supplemental oxygen only, respectively). We intend to recruit 50 patients during their regular follow up appointments (12 months and 24 months after their discharge from the hospital) in our pulmonology outpatient-clinic. Patients fulfilling the criterions of inclusion and exclusion will be included. Patients will undergo a series of measurements on one day in our respiratory physiology laboratory (Respiratory Physiology Laboratory, Department of Pneumology and Intensive Care Medicine, Head: Professor Michael Dreher). Patients will be asked to complete a questionnaire, followed by some examinations comprising spirometry by bodyplethysmography, exercise endurance, capillary blood gas analyses, measurement of maximum inspiratory and expiratory mouth pressures, dynamometric measurement of arm and leg strength, diaphragm ultrasound, magnetic stimulation of the phrenic and lower thoracic nerves with invasive recording of twitch transdiaphragmatic pressure and markers of systemic inflammation based on in depth analyses of blood samples that will be obtained. Based on this data the aim is to develop a model which determines the severity, pathophysiology and clinical consequences of respiratory muscle dysfunction in patients who had been hospitalised for COVID-19. This will potentially prove the importance of a dedicated pulmonologic rehabilitation with respiratory muscle strength training in patients who had been hospitalised for COVID-19.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 20, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 50 patients with survived COVID-19-infection (25 with a severe course requiring mechanical ventilation in the intensive care unit, 25 with a moderate-severe course requiring administration of supplemental oxygen only, respectively)
• Patients aged at least 18 years, who are mentally and physically able to consent and participate into the study

Exclusion Criteria:

• Diagnosis of another disease, which causes a permanent increase in carbon dioxide level in the blood (chronic hypercapnia) or a permanent combined lung weakness (particularly a neuromuscular disease)
• Body-mass-index (BMI) >40
• Expected absence of active participation of the patient in study-related measurements
• Alcohol or drug abuse
• Metal implant in the body that is not MRI compatible (NON MRI compatible pacemaker, implantable defibrillator, cervical implants, e.g. brain pacemakers etc.)
• Slipped disc
• Epilepsy
• Bound to a wheel chair
• Patients who are mentally and physically unable to consent and participate into the study
• Patients in an interdependence or with an employment contract with the principal investigator, Co-PI or his deputy.
• Emergency hospital stay in the last 4 weeks preceding the day of the measurements

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Diaphragm Injury

Intervention

Diagnostic Test:
• Comprehensive assessment of respiratory muscle function.
Comprehensive assessment of respiratory muscle function to the point of its invasive assessment with recordings of twitch transdiaphragmatic pressure in response to magnetic phrenic nerve stimulation and stimulation of the lower thoracic nerve roots.

Locations

Country	Name	City	State
Germany	Jens Spiesshoefer	Aachen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (6)

Balfanz P, Hartmann B, Muller-Wieland D, Kleines M, Hackl D, Kossack N, Kersten A, Cornelissen C, Muller T, Daher A, Stohr R, Bickenbach J, Marx G, Marx N, Dreher M. Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19. PLoS One. 2021 Jan 29;16(1):e0246182. doi: 10.1371/journal.pone.0246182. eCollection 2021. — View Citation

Daher A, Balfanz P, Aetou M, Hartmann B, Muller-Wieland D, Muller T, Marx N, Dreher M, Cornelissen CG. Clinical course of COVID-19 patients needing supplemental oxygen outside the intensive care unit. Sci Rep. 2021 Jan 26;11(1):2256. doi: 10.1038/s41598-021-81444-9. — View Citation

Daher A, Balfanz P, Cornelissen C, Muller A, Bergs I, Marx N, Muller-Wieland D, Hartmann B, Dreher M, Muller T. Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae. Respir Med. 2020 Nov-Dec;174:106197. doi: 10.1016/j.rmed.2020.106197. Epub 2020 Oct 20. — View Citation

Spiesshoefer J, Henke C, Herkenrath S, Brix T, Randerath W, Young P, Boentert M. Transdiapragmatic pressure and contractile properties of the diaphragm following magnetic stimulation. Respir Physiol Neurobiol. 2019 Aug;266:47-53. doi: 10.1016/j.resp.2019.04.011. Epub 2019 Apr 25. — View Citation

Spiesshoefer J, Henke C, Herkenrath S, Randerath W, Brix T, Young P, Boentert M. Assessment of Central Drive to the Diaphragm by Twitch Interpolation: Normal Values, Theoretical Considerations, and Future Directions. Respiration. 2019;98(4):283-293. doi: 10.1159/000500726. Epub 2019 Jul 26. — View Citation

Spiesshoefer J, Herkenrath S, Henke C, Langenbruch L, Schneppe M, Randerath W, Young P, Brix T, Boentert M. Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations. Respiration. 2020;99(5):369-381. doi: 10.1159/000506016. Epub 2020 May 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Twitch transdiaphragmatic pressure in response to supramaximal magnetic stimulation of the phrenic nerve roots	Recording of twitch transdiaphragmatic pressure (Unit: Pressure in cmH2O)	2 years
Primary	Respiratory mouth pressures	Measurement of respiratory (inspiratory and expiratory) mouth pressures (Unit: Pressure in cmH2O)	2 years
Secondary	Diaphragm ultrasound	Comprehensive evaluation of diaphragm excursion (amplitude during tidal breathing, sniff maneuver and maximal inspiration in cm, corresponding velocity in cm/sec, respectively) and thickening on ultrasound (thickness at functional residual capacity, at total lung capactiy in cm), Markers of Diaphragm excursion and thickening will be combined to classify diaphragm function as normal, mildly, moderately or severly impaired.	2 years
Secondary	Exercise intolerance	Comprehensive evaluation of symptoms (breathlesness based on NYHA class, on a visual scale ranging from 1-10, respectively) and exercise capacity (6 minute walking distance). These measurements will be combined to classifiy patients as presenting with exercise intolerance or no exercise intolerance.	2 years
Secondary	Analyses of markers of systemic inflammation (interleukin levels in ng/ml, TNF alpha in ng/ml, CRP in mg/L; immune phenotyping of inflammatory cells, most importantly whilte blood cell subtypes in %)	Analyses of markers of systemic inflammation based on blood samples taken. These measurements will be combined to classify patients as having increased or normal levels of systemic inflammation.	2 years
Secondary	Lung function	Comprehensive assessment of lung function by bodyplethysmography (most importantly forced vital capacity, forced expiratory volume after 1 second, intrathoracic gas volume, residual volume) and capillary blood gas analysis (most importantly pO2 in mmHG and pCO2 in mmHG). These measurements will be combined to classify patients as showing normal, restrictive, obstructive lung function impairment, as being hypoxic, hypercapnic, respectively.	2 years