Evaluation of Direct Antiviral Treatments Against SARS-CoV-2 in Immunocompromised Patients With Covid-19. A G2i Study, National Multicenter Observational and Retrospective From June 2023 to April 2024

NCT ID: NCT06683937

Last Updated: 2025-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-12-01

Study Completion Date

2026-06-01

Brief Summary

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Due to the lower virulence of circulating Omicron variants and the high seroprevalence of anti-SARS-CoV-2 antibodies, the incidence of cases and deaths related to the SARS-CoV-2 virus has significantly decreased in recent months worldwide. However, these infections remain a major public health problem in severely immunocompromised patients, who have decreased vaccine efficacy and are at higher risk of persistent SARS-CoV-2 viral shedding, relapses, secondary invasive fungal infection, intensive care unit hospitalization, and death than non-immunocompromised patients.

The research concerns adult patients at very high risk of severe SARS-CoV-2 disease, suffering from SARS-CoV-2 having resulted in hospitalization in a center participating in the study in France between June 1, 2023 and April 1, 2024 and having received mono- or dual therapy with nirmatrelvir/ritonavir or remdesivir in order to carry out an evaluation of direct antiviral treatments against SARS-CoV-2 in these immunocompromised patients suffering from Covid-19.

The study consists of collecting patient care data from the medical record. Patients will be identified by practitioners at each participating French center.

Detailed Description

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Due to the lower virulence of circulating Omicron variants and the high seroprevalence of anti-SARS-CoV-2 antibodies, the incidence of cases and deaths related to the SARS-CoV-2 virus has significantly decreased in recent months worldwide. However, these infections remain a major public health problem in severely immunocompromised patients, who have decreased vaccine efficacy and are at higher risk of persistent SARS-CoV-2 viral shedding, relapses, secondary invasive fungal infection, intensive care unit hospitalization, and death than non-immunocompromised patients.

The research concerns adult patients at very high risk of severe SARS-CoV-2 disease, suffering from SARS-CoV-2 having resulted in hospitalization in a center participating in the study in France between June 1, 2023 and April 1, 2024 and having received mono- or dual therapy with nirmatrelvir/ritonavir or remdesivir in order to carry out an evaluation of direct antiviral treatments against SARS-CoV-2 in these immunocompromised patients suffering from Covid-19.

Identifying an effective anti-SARS-CoV-2 therapeutic strategy is a real challenge in severely immunocompromised patients because clinicians are faced with chronic carriage and serious complications in these patients, as well as drug interactions with immunosuppressive treatments, the emergence of resistance and the absence of recommendations.

The data currently available in the literature remain heterogeneous and sometimes without sufficient level of evidence. However, some teams have reported in this population the efficacy of repeated or prolonged treatment with nirmatrelvir/ritonavir or even multitherapies combining several antiviral treatments and/or combinations of monoclonal antibodies on persistent carriage of the virus. Thus, some centers recommend prolonged antiviral treatments combining 5 to 10 days of remdesivir with 10 days of nirmatrelvir/ritonavir.

Nirmatrelvir/ritonavir and remdesivir are the currently available antiviral therapies that are still effective against circulating Omicron virus subvariants. It therefore seems important to have more data on their efficacy in monotherapy, dual therapy, or in the case of prolonged treatment.

The study consists of collecting patient care data from the medical record. Patients will be identified by practitioners at each participating French center.

Conditions

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Immunocompromised Patients SARS-CoV-2 Disease

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Study Groups

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Patients

Adult patients at very high risk of severe SARS-CoV-2 disease, hospitalized for SARS-CoV-2 infection from June 2023 to April 2024.

Collection of data from the patient's medical file

Intervention Type OTHER

Collection of data from the patient's medical file

Interventions

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Collection of data from the patient's medical file

Collection of data from the patient's medical file

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Adult patients with SARS-CoV-2 in France, treated in a center participating in the study
* Symptomatic patients for Covid-19 who have received mono- or dual therapy with nirmatrelvir/ritonavir or remdesivir
* SARS-CoV-2 positive by PCR on nasopharyngeal swab, ECBC or bronchoalveolar fluid
* Hospitalization in a ward or day hospital for SARS-CoV-2 infection
* Patients at very high risk of severe form of SARS-CoV-2

* Aggressive lymphomas (all types)
* Acute lymphocytic leukemia
* Acute myeloid leukemia
* Acute promyelocytic leukemia
* T-cell prolymphocytic leukemia
* Primary lymphoma of the central nervous system
* Stem cell transplant
* Light chain amyloidosis
* Chronic lymphocytic leukemia
* Multiple myeloma
* Hematopoietic stem cell transplant
* Solid organ transplant
* Being on the waiting list for an organ transplant
* Primary immunodeficiency;
* HIV patients with CD4 \<200/mm3 or with a detectable viral load
* Lymphopenia \<200/mm3
* Neutropenia \<1000/mm3 for \> 1 week
* Patients receiving long-term immunosuppressive treatment (period of at least 3 months during treatment during infection) with:
* anti-CD20 antibodies
* anti-JAK
* BTK inhibitors
* azathioprine
* cyclophosphamide
* methotrexate
* mycophenolate mofetil
* CAR-T cell gene therapy
* bi-phenotypic therapeutic antibodies
* tacrolimus
* sirolimus
* long-term corticosteroids (prednisone equivalent dose \>5mg for 3 months)

Exclusion Criteria

* Opposition formulated (following receipt of the study information note)
* Patients who received convalescent plasma as first-line treatment for SARS-CoV-2 infection
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cléa Melenotte, M.D.

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Clémentine de La Porte, M.D.

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Locations

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CHU Angers

Angers, , France

Site Status

CHU Caen

Caen, , France

Site Status

Hôpital Pasteur, Colmar

Colmar, , France

Site Status

CHD Vendée (La Roche sur Yon)

La Roche-sur-Yon, , France

Site Status

CHRU Lille

Lille, , France

Site Status

CHU Nord Marseille

Marseille, , France

Site Status

CHU Nantes

Nantes, , France

Site Status

CHU Nîmes Caremeau

Nîmes, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hôpital Necker-Enfants Malades

Paris, , France

Site Status

Hôpital Bichat

Paris, , France

Site Status

CH Périgueux

Périgueux, , France

Site Status

CHU Poitiers

Poitiers, , France

Site Status

CHU Reims

Reims, , France

Site Status

CHU Sud Réunion

Saint-Pierre, , France

Site Status

CHU Toulouse

Toulouse, , France

Site Status

Countries

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France

Central Contacts

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Cléa Dr Melenotte, M.D.

Role: CONTACT

33142192826

Hélène Morel

Role: CONTACT

33171196346

Facility Contacts

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Vincent Dubée, M.D., PhD

Role: primary

Frédéric Rivière, M.D.

Role: primary

Martin Martinot, M.D.

Role: primary

Sophie Leautez-Nainville, M.D.

Role: primary

Thomas Guimard, M.D.

Role: backup

Emmanuel Faure, M.D., PhD

Role: primary

Carole Eldin, M.D.

Role: primary

Benjamin Gaborit, M.D.

Role: primary

Paul Loubet, M.D.

Role: primary

Laura Levi, M.D.

Role: primary

Blandine Denis, M.D.

Role: backup

Cléa Melenotte, M.D.

Role: primary

33142192826

Nathan Peiffer-Smadja, M.D.

Role: primary

Claire Aguilar, M.D.

Role: primary

Gwenaël Le Moal, M.D., PhD

Role: primary

Maxime Hentzien, M.D.

Role: primary

Kevin Diallo, M.D.

Role: primary

Guillaume Martin-Blondel, M.D.

Role: primary

Adrien Chan Sui Ko, M.D.

Role: backup

References

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Bertagnolio S, Thwin SS, Silva R, Nagarajan S, Jassat W, Fowler R, Haniffa R, Reveiz L, Ford N, Doherty M, Diaz J. Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19. Lancet HIV. 2022 Jul;9(7):e486-e495. doi: 10.1016/S2352-3018(22)00097-2. Epub 2022 May 10.

Reference Type BACKGROUND
PMID: 35561704 (View on PubMed)

DeWolf S, Laracy JC, Perales MA, Kamboj M, van den Brink MRM, Vardhana S. SARS-CoV-2 in immunocompromised individuals. Immunity. 2022 Oct 11;55(10):1779-1798. doi: 10.1016/j.immuni.2022.09.006. Epub 2022 Sep 13.

Reference Type BACKGROUND
PMID: 36182669 (View on PubMed)

MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM. Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform. Lancet Rheumatol. 2022 Jul;4(7):e490-e506. doi: 10.1016/S2665-9913(22)00098-4. Epub 2022 Jun 9.

Reference Type BACKGROUND
PMID: 35698725 (View on PubMed)

Evans RA, Dube S, Lu Y, Yates M, Arnetorp S, Barnes E, Bell S, Carty L, Evans K, Graham S, Justo N, Moss P, Venkatesan S, Yokota R, Ferreira C, McNulty R, Taylor S, Quint JK. Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study. Lancet Reg Health Eur. 2023 Oct 13;35:100747. doi: 10.1016/j.lanepe.2023.100747. eCollection 2023 Dec.

Reference Type BACKGROUND
PMID: 38115964 (View on PubMed)

Other Identifiers

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APHP241194

Identifier Type: -

Identifier Source: org_study_id

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