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.

Covid19 Clinical Trial

Official title:

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 Prospective Cohort.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04885452
• Other study ID #: ANRS0003S COCOPREV
• Status: Recruiting
• Start date: September 21, 2021
• Est. completion date: June 2023

Study information

• Verified date: January 2022
• Source: ANRS, Emerging Infectious Diseases
• Contact: Youri Yordanov, Dr
• Phone: 01 71 97 08 69
• Email: youri.yordanov[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

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

Locations

Country	Name	City	State
France	CH Agen-Nerac	Agen
France	CHU d'Angers	Angers
France	CHR Metz-Thionville	Ars-Laquenexy
France	Hôpital Avicenne	Bobigny
France	CHU de Bordeaux	Bordeaux
France	CHU Gabriel Montpied	Clermont-Ferrand
France	Centre Hospitalier Sud Francilien - Hématologie	Corbeil-Essonnes
France	Centre Hospitalier Sud Francilien - Néphrologie	Corbeil-Essonnes
France	CHU de Dijon	Dijon
France	CHU de Martinique	Fort-de-France
France	Hôpital Bicêtre - Médecine interne	Le Kremlin-Bicêtre
France	Hôpital Bicêtre - SMIT	Le Kremlin-Bicêtre
France	CHU de Limoges	Limoges
France	Hospices Civils de Lyon (HCL)	Lyon
France	CHU de Montpellier	Montpellier
France	CHRU de Nancy	Nancy
France	CHU de Nantes	Nantes
France	CHU de Nîmes	Nîmes
France	Hôpital Bichat Claude-Bernard	Paris
France	Hôpital Bichat Claude-Bernard - SAU	Paris
France	Hôpital Lariboisière - SAU SMUR	Paris
France	Hôpital Lariboisière - SMIT	Paris
France	Hôpital Pitié-Salpêtrière	Paris
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Antoine - SAU	Paris
France	Hôpital Saint-Louis	Paris
France	Hôpital Tenon	Paris
France	Hôpital Universitaire Necker Enfants Malades	Paris
France	Hôpitaux Cochin - Port Royal	Paris
France	CHI Poissy St Germain en Laye	Poissy
France	CHU de Poitiers	Poitiers
France	CHU de Rennes	Rennes
France	CH de Tarbes	Tarbes
France	CHU de Toulouse	Toulouse
France	CHU de Toulouse - IUCT - Oncopole	Toulouse
France	CH de Tourcoing	Tourcoing
France	CHRU de Tours - Hôpital Bretonneau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of patients hospitalized whatever the reason		Month 1 and 3
Secondary	Percentage of patients with an WHO score >= 5		Month 1
Secondary	Percentage of patients staying in an Intensive Care Unit in the month following symptoms' onset		Month 1
Secondary	Percentage of patients who died from COVID-19 complications and any other reason		Month 1
Secondary	Percentage of patients presenting a adverse event and percentage of treatment discontinuation caused by those adverse events		Month 1
Secondary	Time between first symptoms and treatment and the reasons for this delay		Day 0
Secondary	Virological response	Percentage of virological response defined by CT>=31 or negative PCR test +	Day 7 for ambulatory patients, Day 3, 5 and 7 for hospitalized patients
Secondary	Virological criteria linked to the emergence of resistance	Percentage of patients included developing resistance variants, genotypic and phenotypic characterization of resistance variants	from inclusion until a negative PCR test or Ct =31 is obtained
Secondary	Percentage of patients with positive anti-N and anti-S serology		Day 0 and Month 3
Secondary	anti-S antibody level		Day 0 and Month 3
Secondary	Flow cytometry cartography of myeloid response	Flow cytometry cartography of myeloid (functional subtypes of monocytes and dendritic cells) response	Day 0, 7 and Month 1
Secondary	Flow cytometry cartography of T-lymphocyte response	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	Day 0, 7 and Month 1
Secondary	Flow cytometry cartography of B-lymphocyte response	Flow cytometry cartography of B-lymphocyte (transitional, naïve, memory T-lymphocyte with or without isotypic switching, plasmablasts) response	Day 0, 7 and Month 1
Secondary	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
Secondary	Clinical and biological predictors (clinical parameters, treatment received, virological criteria (cycle threshold (CT), variants) of the onset of complications from COVID19, hospitalization, death	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	from inclusion until the end of the follow-up (Month 1 or Month 3)
Secondary	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	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	from inclusion until the end of the follow-up (Month 1 or Month 3)
Secondary	Clinical and biological predictors (clinical parameters, treatment received, virological criteria) of viral response (viral genotypes, emergence of resistant strains)	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	from inclusion until the end of the follow-up (Month 1 or Month 3)