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

Not yet recruiting

• Conditions: Immunocompromised Patients; SARS-CoV-2 Disease

• Registration Number: NCT06683937
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-11-05
• Study First Submitted QC: 2024-11-09
• Last Update Submitted: 2024-11-09
• Study First Posted: 2024-11-12
• Last Update Posted: 2024-11-12
• Study Start: 2024-12-01
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

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)

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Clinical evolution of immunocompromised patients receiving remdesivir and/or nirmatrelvir/ritonavir as curative treatment for COVID-19	37 days	Evolution of the patient's modified (suitable for immunocompromised patients) Ordinal Scale for Clinical Improvement (OSCI) of the World Health Organization (WHO) (score from 0 - non infected patient to 8 - deceased patient) from the initiation of treatment to 30 days (+7 days) following the first line of therapy.

Secondary Outcome Measures

Name	Time	Method
Mortality at 30 days of diagnosis	30 days	Mortality at 30 days of diagnosis
Tolerance of antiviral treatments against SARS-CoV-2	6 months	Rate of serious side effects within 6 months (grade 3 and 4 on adverse event scale).
Evaluate virological evolution	60 days	Decrease or negativity of PCR between D2 and D30 following the first line of anti-SARS-CoV-2 therapy, then at D60.
Evaluate radiological evolution	90 days	Reduction or disappearance of radiological lung lesions after the first line of therapy.
Clinical relapse at discharge from hospital, at D30 and D60	90 days	Modified (suitable for immunocompromised patients ) OSCI score (Ordinal Scale for Clinical Improvement of the World Health Organization, score from 0 - non infected patient to 8 - deceased patient)at hospital discharge, D30 and D60. Maximum modified OSCI score between H48 and D30.
Identified factors associated with favorable evolution	90 days	Description of clinical evolution adjusted for age and other variables of interest.
Infectious complications and secondary non-infectious complications	90 days	Incidence of infectious complications (aspergillosis and bacterial infections) and secondary non-infectious complications.; Collection of the following elements: * Use of a second line of therapy (antivirals and plasma therapy) specifying the time after the first line; * occurrence of complications during the initial hospitalization after the first line of therapy: pulmonary embolism, hospitalization in the Intensive Care Unit, probable or proven invasive fungal infections (aspergillosis, mucormycosis with initiation of antifungal treatment), bacterial infection (antibiotics initiated); * persistence of viral carriage (\> 3 weeks and \>8 weeks)

Trial Locations

Locations (16)

CHU Angers; 🇫🇷 Angers, France

CHU Caen; 🇫🇷 Caen, France

Hôpital Pasteur, Colmar; 🇫🇷 Colmar, France

CHD Vendée (La Roche sur Yon); 🇫🇷 La Roche sur Yon, France

CHRU Lille; 🇫🇷 Lille, France

CHU Nord Marseille; 🇫🇷 Marseille, France

CHU Nantes; 🇫🇷 Nantes, France

CHU Nîmes Caremeau; 🇫🇷 Nîmes, France

Hôpital Saint-Louis; 🇫🇷 Paris, France

Hôpital Necker-Enfants Malades; 🇫🇷 Paris, France

Hôpital Bichat; 🇫🇷 Paris, France

CHU Poitiers; 🇫🇷 Poitiers, France

CH Périgueux; 🇫🇷 Périgueux, France

CHU Reims; 🇫🇷 Reims, France

CHU Sud Réunion; 🇫🇷 Saint-Pierre, France

CHU Toulouse; 🇫🇷 Toulouse, France