Clinical trial NCT06683937: 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
Official title: 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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Immunocompromised Patients
SARS-CoV-2 Disease
Keywords: Immunocompromised patients
SARS-CoV-2 disease
Mono- or dual therapy with nirmatrelvir/ritonavir or remdesivir
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-11-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients at very high risk of severe SARS-CoV-2 disease, hospitalized for SARS-CoV-2 infection from June 2023 to April 2024 in France.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical evolution of immunocompromised patients receiving remdesivir and/or nirmatrelvir/ritonavir as curative treatment for COVID-19
timeFrame: 37 days
Secondary outcomes:
measure: Mortality at 30 days of diagnosis
timeFrame: 30 days
measure: Tolerance of antiviral treatments against SARS-CoV-2
timeFrame: 6 months
measure: Evaluate virological evolution
timeFrame: 60 days
measure: Evaluate radiological evolution
timeFrame: 90 days
measure: Clinical relapse at discharge from hospital, at D30 and D60
timeFrame: 90 days
measure: Identified factors associated with favorable evolution
timeFrame: 90 days
measure: Infectious complications and secondary non-infectious complications
timeFrame: 90 days
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Caen
country: France
facility: CHU Caen
city: Colmar
country: France
facility: Hôpital Pasteur, Colmar
city: La Roche sur Yon
country: France
facility: CHD Vendée (La Roche sur Yon)
city: Lille
country: France
facility: CHRU Lille
city: Marseille
country: France
facility: CHU Nord Marseille
city: Nantes
country: France
facility: CHU Nantes
city: Nîmes
country: France
facility: CHU Nîmes Caremeau
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Paris
country: France
facility: Hôpital Bichat
city: Poitiers
country: France
facility: CHU Poitiers
city: Périgueux
country: France
facility: CH Périgueux
city: Reims
country: France
facility: CHU Reims
city: Saint-Pierre
country: France
facility: CHU Sud Réunion
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Cléa Melenotte, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Clémentine de La Porte, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.