Prevention of COVID-19 Complications in High-risk Subjects Infected by SARS-CoV-2 and Eligible for Treatment Under a Cohort ATU ('Autorisation Temporaire d'Utilisation') OR or Authorisation for Early Access (AAP). A Prospectvie Cohort.
Study Details
Study Description
Brief Summary
This is a prospective, multicentric, non comparative study aiming to evaluate the clinical and virological evolution of high-risk patients infected with SARS-CoV-2 treated withtin the framework of a cohort ATU ('Autorisation temporaire d'utilisation') or authorisation for early access (AAP) delivered by the French drug agency (ANSM).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients treated with casirivimab/imdevimab according to the ATU protocol
|
Other: biobank
Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood)
For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC)
Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14)
Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5
|
| Patients treated with bamlanivimab/etesevimab according to the ATU protocol
|
Other: biobank
Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood)
For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC)
Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14)
Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5
|
| Patients treated with Xevudy according to the authorisation for early access (AAP) protocol
|
Other: biobank
Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood)
For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC)
Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14)
Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5
|
| Patients treated with Paxlovid according to the authorisation for early access (AAP) protocol
|
Other: biobank
Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood)
For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC)
Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14)
Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5
|
Outcome Measures
Primary Outcome Measures
- Percentage of patients hospitalized (if the patient was outpatient) or whose hospitalization was extended for complications from COVID-19 within 1 month of symtoms' onset. [Month 1]
Secondary Outcome Measures
- Percentage of patients hospitalized whatever the reason [Month 1 and 3]
- Percentage of patients with an WHO score >= 5 [Month 1]
- Percentage of patients staying in an Intensive Care Unit in the month following symptoms' onset [Month 1]
- Percentage of patients who died from COVID-19 complications and any other reason [Month 1]
- Percentage of patients presenting a adverse event and percentage of treatment discontinuation caused by those adverse events [Month 1]
- Time between first symptoms and treatment and the reasons for this delay [Day 0]
- Virological response [Day 7 for ambulatory patients, Day 3, 5 and 7 for hospitalized patients]
Percentage of virological response defined by CT>=31 or negative PCR test +
- Virological criteria linked to the emergence of resistance [from inclusion until a negative PCR test or Ct ≥31 is obtained]
Percentage of patients included developing resistance variants, genotypic and phenotypic characterization of resistance variants
- Percentage of patients with positive anti-N and anti-S serology [Day 0 and Month 3]
- anti-S antibody level [Day 0 and Month 3]
- Flow cytometry cartography of myeloid response [Day 0, 7 and Month 1]
Flow cytometry cartography of myeloid (functional subtypes of monocytes and dendritic cells) response
- Flow cytometry cartography of T-lymphocyte response [Day 0, 7 and Month 1]
Flow cytometry cartography of T-lymphocyte (conventional T-lymphocytes by identifying naïve, memory and effector Th1, Th2, Tfh and Th17 T-lymphocytes, NK and gamma-delta T-lymphocytes, regulatory T-lymphocytes; surface and intracellular markers) response
- Flow cytometry cartography of B-lymphocyte response [Day 0, 7 and Month 1]
Flow cytometry cartography of B-lymphocyte (transitional, naïve, memory T-lymphocyte with or without isotypic switching, plasmablasts) response
- Dosing of a wide range of cytokines and chemokines (IFNalpha, IFNgamma, IL-6, IL-1, IL-8, IL-15, IL-18, IL1-RA, IL-7, IL-10, CXCL10, CXCL13, CCL2 and CCL3) using the Meso Scale Discovery approach [Day 0, 7 and Month 1]
- Clinical and biological predictors (clinical parameters, treatment received, virological criteria (cycle threshold (CT), variants) of the onset of complications from COVID19, hospitalization, death [from inclusion until the end of the follow-up (Month 1 or Month 3)]
Identication of clinical and biological predictors of the onset of complications from COVID19, hospitalization, death by a logistic model or survival model (RMST): the response variable is the occurrence of a complication, hospitalization, death or the average survival at 1 month on these different criteria; the covariates are the parameters at inclusion, the treatment received, the virological criteria (CT, variants) which can be considered as a time-dependent covariate
- Clinical and biological predictive factors (clinical parameters, treatment received, virological criteria (cycle threshold (CT), variants)) linked to the neutralizing serological response: non-response, duration of the response [from inclusion until the end of the follow-up (Month 1 or Month 3)]
Identification of clinical and biological predictive factors (clinical parameters, treatment received, virological criteria (cycle threshold (CT), variants)) linked to the neutralizing serological response: non-response, duration of the response by a logistic model or mixed model for repeated measures
- Clinical and biological predictors (clinical parameters, treatment received, virological criteria) of viral response (viral genotypes, emergence of resistant strains) [from inclusion until the end of the follow-up (Month 1 or Month 3)]
Identification of clinical and biological predictive factors related to the virological response (viral genotypes, emergence of resistant strains) by a logistic model: the response variable is RT-PCR negativation at D7 (or CT≥31), the covariates are the parameters at inclusion, the treatment received, the virological criteria at baseline
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults with the criteria for COVID-19 treatment within the French compassionate program (ATU/AAP)
-
Adults covered by the French social health coverage
-
Adults who signed the informed consent form
Exclusion Criteria:
-
Exclusion criteria described in the French compassionate program (ATU/AAP)
-
Patient participating in another biomedical research with an exclusion period ongoing at inclusion
-
Vulnerable patient (adults legally protected: under judicial protection, guardianship, or supervision, persons deprived of their liberty)
-
Pregnant or breastfeeding woman
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CH Agen-Nerac | Agen | France | ||
| 2 | CHU d'Angers | Angers | France | ||
| 3 | CHR Metz-Thionville | Ars-Laquenexy | France | ||
| 4 | Hôpital Avicenne | Bobigny | France | ||
| 5 | CHU de Bordeaux | Bordeaux | France | 33076 | |
| 6 | CHU Gabriel Montpied | Clermont-Ferrand | France | ||
| 7 | Centre Hospitalier Sud Francilien - Hématologie | Corbeil-Essonnes | France | 91106 | |
| 8 | Centre Hospitalier Sud Francilien - Néphrologie | Corbeil-Essonnes | France | 91106 | |
| 9 | CHU de Dijon | Dijon | France | ||
| 10 | CHU de Martinique | Fort-de-France | France | 97261 | |
| 11 | Hôpital Bicêtre - Médecine interne | Le Kremlin-Bicêtre | France | 94275 | |
| 12 | Hôpital Bicêtre - SMIT | Le Kremlin-Bicêtre | France | 94275 | |
| 13 | CHU de Limoges | Limoges | France | ||
| 14 | Hospices Civils de Lyon (HCL) | Lyon | France | ||
| 15 | CHU de Montpellier | Montpellier | France | ||
| 16 | CHRU de Nancy | Nancy | France | 54511 | |
| 17 | CHU de Nantes | Nantes | France | ||
| 18 | CHU de Nîmes | Nîmes | France | ||
| 19 | Hôpital Lariboisière - SMIT | Paris | France | 75010 | |
| 20 | Hôpital Saint Antoine | Paris | France | 75012 | |
| 21 | Hôpital Bichat Claude-Bernard | Paris | France | 75018 | |
| 22 | Hôpital Tenon | Paris | France | 75020 | |
| 23 | Hôpital Bichat Claude-Bernard - SAU | Paris | France | ||
| 24 | Hôpital Lariboisière - SAU SMUR | Paris | France | ||
| 25 | Hôpital Pitié-Salpêtrière | Paris | France | ||
| 26 | Hôpital Saint Antoine - SAU | Paris | France | ||
| 27 | Hôpital Saint-Louis | Paris | France | ||
| 28 | Hôpital Universitaire Necker Enfants Malades | Paris | France | ||
| 29 | Hôpitaux Cochin - Port Royal | Paris | France | ||
| 30 | CHI Poissy St Germain en Laye | Poissy | France | ||
| 31 | CHU de Poitiers | Poitiers | France | ||
| 32 | CHU de Rennes | Rennes | France | ||
| 33 | CH de Tarbes | Tarbes | France | ||
| 34 | CHU de Toulouse - IUCT - Oncopole | Toulouse | France | ||
| 35 | CHU de Toulouse | Toulouse | France | ||
| 36 | CH de Tourcoing | Tourcoing | France | ||
| 37 | CHRU de Tours - Hôpital Bretonneau | Tours | France |
Sponsors and Collaborators
- ANRS, Emerging Infectious Diseases
Investigators
- Principal Investigator: Youri Yordanov, Dr, Saint Antoine Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ANRS0003S COCOPREV