PATIENTS

Clinical trials are scientific studies designed to evaluate new treatments or medical interventions. They are intended to verify safety and test effectiveness in sick people. People included in these studies are all volunteers.

At the beginning of the COVID-19 epidemic, no specific treatment was recommended for hospitalized Covid-19 patients and for the prevention of the progression of the disease. Several trials have therefore been launched to scientifically evaluate molecules likely to provide a benefit in the management of severe forms of Covid-19 and to prevent the onset of severe forms.

The World Health Organization recommends to systemically evaluate experimental therapeutics suggested by researchers or clinicians, in collaborative clinical trials.

Discovery is aimed to find effective and safe treatments for COVID-19.

DisCoVeRy has implemented a new a new therapeutic arm to test a long-acting antibody (LAAB) combination developed by AstraZeneca. Click here for more information.

The initial design was composed of four different treatments evaluated in adults (≥18-year-old) hospitalized for COVID-19, added to standard cares (oxygen therapy, drugs in prevention of phlebitis and pulmonary embolism, and dexamethasone which reduces inflammation and lung damage) and compared to standard cares alone. Their efficacy was evaluated 15 days after treatment initiation. Click here for more information.

This study is a multi-centre/country trial involving ten European countries, led by the French national institute for Health and Medical Research (Inserm), and is conducted in partnership with the Solidarity trial, coordinated by the World Health Organisation (WHO).

The European Commission supports the European extension of the DisCoVeRy trial through the 5 years funding of a European network for research and preparedness for pandemics and emerging infectious diseases – EU-RESPONSE. EU-RESPONSE is coordinated by Inserm.

The new treatment arm evaluating a long-acting antibody (LAAB) combination developed by AstraZeneca has a high neutralising power and is active on all known variants. It is the first treatment arm in Discovery testing a recently developed, specific anti-SARS-CoV-2.

The four treatments previously included in DisCoVeRy are re-purposed therapeutics, initially indicated in other viral infections or immune diseases. They exhibit anti Sars-CoV2 activity in vitro or in mouse models. Some of them were used by physicians for the management of severe forms of Covid-19 without official recommendations.

• Lopivanir-Ritonavir: two antiviral drugs indicated for HIV
• Lopivnir-Ritonavir + Interferon Beta: two antiviral drugs indicated for HIV plus an extra antiviral molecule naturally produced by the body in case of viral infection and used to limit inflammation in multiple sclerosis.
• Remdesivir: antiviral drug initially developed against Ebola virus.
• Hydroxychloroquine : anti-inflammatory drug indicated in several autoimmune diseases such as lupus or rheumatoid arthritis.

Given the severity of Covid-19 in many patients, it is important to have treatments and, if possible, several therapeutic options to meet all needs. It is anticipated that vaccination efficacy may be decreased in some subgroups of patients. Others will not be able to be vaccinated for health or personal reasons. To date, besides optimization of standard of care, there is still no specific treatment of COVID-19 requiring hospitalization that has achieved a reduction in overall mortality.

You must be hospitalized for Covid-19 with respiratory symptoms and need of oxygen therapy.

Upon hospitalization, your doctor will propose you to participate in the trial if you present inclusion criteria without exclusion criteria (such as severe kidney or hepatic failure for example). Information about the study and its course will be given to you by your attending physician. If you agree to participate, your consent must be signed on a specific paper. Women of childbearing potential must agree to use contraception for the duration of the study.

An emergency consent procedure with the legal guardian or relatives of the patient has been put in place for patients who are unable to consent.

The duration of your participation will be 456 days after signing the consent.

Participating in this trial does not modify the terms of your cares. You will take an extra medicine at the expense of the hospital and give your consent for the collection and processing of your personal health data (biological samples, clinical data…) for the purpose of research objectives. If you are discharged from hospital before day 29 after enrolment, you will be asked to attend a medical consultation at the hospital at days 29 and 90. 25% of patients enrolled in the trial will be asked to attend additional medical consultations at days 180 and 365. At day 456, all patients will be contacted by phone.

You can, at any moment of the trial, revoke your consent. There will be no consequence on your medical care and your follow up. We simply ask that you inform the referent physician. You will not have to justify your decision. Your referent physician may also decide to discharge you from the protocol because of medical needs incompatible with the protocol.

However, the results of the study will be significant only if a large number of volunteers complete the study. For the ones who are withdrawn from the protocol, biological samples collected prior to withdrawal will be anonymously analysed then destroyed, and the data collection will be interrupted.

At the time of inclusion, we don’t know the benefit of the evaluated drugs compared to standard of care alone in severe forms of COVID-19. No benefit from your participation in this research study must be expected by you personally. By agreeing to participate, you will contribute to improving knowledge of the disease, opening up new therapeutic approaches against coronavirus infections.

Your participation involves the collection of your personal data (clinical and biological samples), anonymously encoded by a numerical code. They will be transmitted to the investigator and/or the research coordinating team or to persons acting on behalf of Inserm in France. They may also be transmitted to French or foreign third parties (health authorities, other research organisations, etc.) under conditions that ensure their confidentiality and anonymity, unless you object. The processing of your data is placed under the responsibility of the French National Institute for Health and Medical research (Inserm).

All the information regarding the purpose of sharing your data are available on the CIC1425  http://recherche-hupnvs.aphp.fr/structures-de-recherche/centre-dinvestigation-clinique-module-epidemiologie-clinique-cic-ec-1425/

According to the law, you have the right to :

• request access, rectification or limitation of your data collected in the course of research.
• The right to object to the collection and transmission of your data covered by medical secrecy.
• The right to withdraw your consent to the collection of your data at any time.

You can assert these rights with the person who obtained your consent and who solely knows your identity. In case of difficulty in exercising your rights, you may contact the Inserm Data Protection Delegate by e-mail (dpo@inserm.fr ) or by post (Data Protection Delegate, 101 rue de Tolbiac, 75 013 Paris). You also have the right to lodge a complaint with the Commission Nationale de l’Informatique et des Libertés – CNIL, the French personal data control authority (for more information on this subject, go to www.cnil.fr).

Participating in this study is completely free of honorary. The hospital supports all the costs associated with your inclusion and follow up.