Support for the Resumption of Training of High-level Athletes Post-epidemic COVID-19

COVID-19 Clinical Trial

— ASCCOVID19  

Official title:

Support for the Resumption of Training of High-level Athletes Post-epidemic COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04936503
• Other study ID #: CHUBX 2020/16
• Status: Completed
• Phase: N/A
• Start date: June 18, 2020
• Est. completion date: March 2, 2021

Study information

• Verified date: June 2021
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

As of March 2020, COVID-19 has become a global pandemic, halting athletic competition worldwide. Reports from China show a high prevalence of cardiac involvement in patients with severe SARS-CoV-2 infection. These cardiac forms were found to be closely associated with adverse outcomes. The use of Magnetic resonance Imaging (MRI) had allowed to show that cardiac dysfunction could be mediated by myocardial inflammation (i.e. myocarditis). The direct implication of the virus was demonstrated with Severe Acute Respiratory Syndrome (SARS)-CoV-2 being detected on myocardial biopsies in a patient with severe heart failure. The experience with other viruses causing acute myocarditis shows that there is a high rate of undetected injuries. Indeed, although severe heart failure can be present at the acute stage, acute viral myocarditis is most commonly pauci or asymptomatic, but still leaving occult myocardial scars visible on MRI, and exposing to higher risks of ventricular arrhythmia and sudden cardiac death over the long term. Although athletes are younger and have fewer comorbidities than the general population and therefore are at lower risk for severe disease or death, there is a critical and urgent need to assess the prevalence of occult scars in the population of high-level athletes returning to training after the SARS-CoV-2 pandemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 984
• Est. completion date: March 2, 2021
• Est. primary completion date: March 2, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• High level athlete,
• Of both sexes and age = 18 years,
• Affiliated to or beneficiary of a social security system,
• Free, informed, written consent signed by the participant and the investigating physician (no later than the day of inclusion and before any examination required by the research),
• Effective method of contraception for women with childbearing capacity.

Exclusion Criteria:

• Minor,
• History of ventricular arrhythmia, myocarditis, identified coronary artery disease or documented myocardial fibrosis,
• Pregnant or breastfeeding women,
• Person unable to give informed consent,
• Person deprived of liberty by judicial or administrative decision,
• Adults subject to a legal protection measure (guardianship, curator, safeguard of justice).

Specific exclusion criteria for the MRI component (Contraindications):

• Subject with an implantable pacemaker or defibrillator, intraocular metallic foreign body, intracranial metallic clip, pre 6000 Starr-Edwards type cardiac valve prosthesis, or biomedical device such as insulin pump or neurostimulator,
• Hypersensitivity to gadolinium or to one of the excipients of the contrast product used,
• Claustrophobic subjects or those unable to remain in an immobile lying position for 30 minutes,
• Renal insufficiency with creatinine clearance of less than 30 ml/min,
• A patient whose shoulder width does not allow installation in the MRI machine.

Related Conditions & MeSH terms

• COVID-19
• Myocarditis

Intervention

Diagnostic Test:
• Resting electrocardiogram
An ECG at rest is performed for all participants at Day 0. A centralized reading is performed by one of the 6 expert cardiologists participating in the research.
• Stress test
In case of positive COVID-19 serology and/or positive COVID-19 RT-PCR and/or new ECG abnormality and/or positive questionnaire, a stress test is performed.
• Cardiac echocardiography
In case of positive COVID-19 serology and/or positive COVID-19 RT-PCR and/or new ECG abnormality and/or positive questionnaire, a Cardiac echocardiography is performed.
• Cardiac rhythm monitoring
In case of positive COVID-19 serology and/or positive COVID-19 RT-PCR and/or new ECG abnormality and/or positive questionnaire, a Cardiac rhythm monitoring is performed.

Other:
• Questionnaire
To determine the rhythmic risk of athletes

Device:
• Injected Cardiac MRI
High resolution MRIs is performed on 200 athletes : 100 athletes without rhythmic abnormalities (50 individuals with positive COVID-19 status and 50 individuals with negative COVID-19 status) 100 athletes with rhythmic abnormalities (50 individuals with positive COVID-19 status and 50 individuals with negative COVID-19 status)

Biological:
• Blood sampling for biobank
For all athletes included at the D0 inclusion visit, a centralized COVID-19 serology is performed to search for biomarkers associated with the occurrence of myocardial fibrosis: analysis of genetic determinants in relation to cardiac damage. For athletes who have performed MRI: Search for biomarkers associated with the occurrence of myocardial fibrosis: analyses of low-grade inflammation markers (cytokine assay and fibrosis markers).

Locations

Country	Name	City	State
France	Training center Soyaux Angoulême XV Rugby	Angoulême
France	Training Center Stade Aurillacois	Aurillac
France	Aviron Bayonnais Rugby Pro Training Center	Bayonne
France	Union Bordeaux-Bègles training center	Bègles
France	Biarritz Olympique Pays Basque training center	Biarritz
France	Bordeaux University Hospital - CRB medical office - Hôpital du Tondu	Bordeaux
France	Bordeaux University Hospital - Service UDH - Hôpital Pellegrin	Bordeaux
France	CABCL Rugby Training Center	Brive-la-Gaillarde
France	US Carcassonne Rugby training center	Carcassonne
France	Union Sportive Colomiers Rugby training center	Colomiers
France	FC Grenoble Rugby training center	Grenoble
France	Stade Rochelais Rugby training center	La Rochelle
France	Racing92 training center	Le Plessis-Robinson
France	AS Montauban Rugby training center	Montauban
France	US Nevers Rugby training center	Nevers
France	Stade Français training center	Paris
France	Section Paloise Rugby training center	Pau
France	USAP Training Center	Perpignan
France	Training center Valence Romans Drôme Rugby	Romans-sur-Isère
France	Castres Olympique training center	Saix
France	Stade Toulousain Rugby training center	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of rhythmic risk markers bye the questionnaire	Questionnaire looking for heart palpitations, chest pain/pressure and shortness of breath.	Day 0
Primary	Evaluation by resting ECG of rhythmic risk marker : repolarization disorders	Presence or absence of repolarization disorders	Day 0
Primary	Evaluation by resting ECG of rhythmic risk marker : inverted T waves	Presence or absence of inverted T waves	Day 0
Primary	Evaluation by resting ECG of rhythmic risk marker : ST segment abnormalities	Presence or absence of ST segment abnormalities	Day 0
Primary	Evaluation by resting ECG of rhythmic risk marker : QRS fragmentation	Presence or absence of QRS fragmentation	Day 0
Primary	Evaluation by resting ECG of rhythmic risk marker : ventricular extrasystoles (VES)	Presence or absence of VES. Ventricular extrasystoles especially with short coupling (<300ms), falling on the T wave, width > 160ms, complex forms (repetitive, several morphologies, instantaneous cycle >200bpm)	Day 0
Primary	Evaluation by resting ECG of rhythmic risk marker : ventricular tachycardia (VT)	Presence or absence of VT.	Day 0
Primary	Presence of rhythmic risk markers bye the stress test	VES, especially with short coupling (<300ms), falling on the T wave, width > 160ms, complex shapes (repetitive, several morphologies, instantaneous cycle >200bpm), ventricular tachycardias (VT). The analysis focus on the exercise period, and the recovery period. Ventricular arrhythmias will be quantified.	Day 0
Primary	Presence of rhythmic risk markers bye ECG holter	VES, especially with short coupling (<300ms), falling on the T wave, width > 160ms, complex shapes (repetitive, multiple morphologies, instantaneous cycle >200bpm), ventricular tachycardias (VTs). Ventricular arrhythmias are quantified.	Day 0
Primary	Presence of rhythmic risk markers bye ECG monitoring during games and trainings	In case of moderate arrhythmia on stress test and/or Holter ECG, ECG monitoring during training sessions and matches is carried out with analysis of the tracings collected, in search of more sustained arrhythmia, particularly at the ventricular level.	Day 0
Primary	Presence of rhythmic risk markers by pharmacological tests and/or electrophysiological exploration	If the risk is perceived as very high, pharmacological tests (Isuprel®) and/or electrophysiological exploration may be performed during hospitalization, in search of dangerous rhythm disorders, particularly at the ventricular level.	Day 0
Secondary	Presence of myocardial fibrosis by injected MRI	In order to compare the prevalence of myocardial fibrosis between COVID-19 positive and COVID-19 negative individuals in high level athletes with or without rhythmic risk, a high resolution MRI is performed. The examinations is performed on 1.5 or 3T MRI systems equipped with specific antennas for cardiology. The sequence used to detect occult scars is a late enhancement sequence performed at least 15 minutes after injection of gadolinium salts, using a free-breathing 3D method, for a minimum spatial resolution of 2.5x1.25x1.25mm. The images are reviewed by a core lab at the Bordeaux University Hospital. The presence or absence of myocardial fibrosis is evaluated.	Month 3
Secondary	Presence of transmural localization of myocardial fibrosis by injected MRI	In order to compare the prevalence of myocardial fibrosis between COVID-19 positive and COVID-19 negative individuals in high level athletes with or without rhythmic risk, a high resolution MRI is performed. The examinations is performed on 1.5 or 3T MRI systems equipped with specific antennas for cardiology. The sequence used to detect occult scars is a late enhancement sequence performed at least 15 minutes after injection of gadolinium salts, using a free-breathing 3D method, for a minimum spatial resolution of 2.5x1.25x1.25mm. The images are reviewed by a core lab at the Bordeaux University Hospital. The presence or absence of transmural localization is evaluated.	Month 3
Secondary	Measurement of cardiac scar size by injected MRI	In order to compare the prevalence of myocardial fibrosis between COVID-19 positive and COVID-19 negative individuals in high level athletes with or without rhythmic risk, a high resolution MRI is performed. The examinations is performed on 1.5 or 3T MRI systems equipped with specific antennas for cardiology. The sequence used to detect occult scars is a late enhancement sequence performed at least 15 minutes after injection of gadolinium salts, using a free-breathing 3D method, for a minimum spatial resolution of 2.5x1.25x1.25mm. The images are reviewed by a core lab at the Bordeaux University Hospital. The size of scars is measured in milliliters (mL).	Month 3
Secondary	Search for constitutional genetic biomarkers	identification by sequencing of genetic variants that could have an impact on the occurrence of a severe form in individuals infected with SARS-CoV-2.	Month 5
Secondary	Research of inflammation markers	Th1/Th2/activation/inflammation/apoptosis markers are measured in sera by a Luminex test allowing the detection of 10 analytes with a commercial kit according to the manufacturer's instructions	Month 5