Trials

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate 5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8(th), 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8(th), 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15(th), 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15(th), 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22(nd), 2020 (Identifier: NCT04356495): and on EudraCT on April 10(th), 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2)

Cartographie de l'occupation du sol sur le bassin de Thau

Dans le contexte actuel de gestion intégrée du littoral, la croissance démographique et l’augmentation de la pression foncière sur le bassin de Thau font de ce territoire un enjeu important, se répercutant sur l’occupation du sol. Pour faire face à ces enjeux, les collectivités territoriales du territoire de Thau ont confié au SMBT à partir de 2006 l’élaboration conjointe de plusieurs instruments de planification afin de mener une approche intégrée du développement territorial au travers du SCoT, du SAGE et d’une procédure Natura 2000. L’objectif de cette contribution est de présenter la méthodologie opérationnelle développée pour cartographier l’occupation du sol initiale 2012/2013 à partir d’images Pléiades sur le bassin de Thau. Cette cartographie constituera une donnée d’entrée pour nourrir l’observatoire du territoire de Thau et sera adaptée à la mise en ½uvre des instruments de planification. La méthodologie a été scindée en deux parties, une première partie de photo-interprétation pour cartographier les espaces artificialisés et leurs évolutions sur plusieurs années et une seconde partie sur une approche par classification orientée-objet sur les espaces agricoles et les milieux naturels. La démarche procure un état actualisé de l’occupation du sol selon une typologie à 4 niveaux adaptée de Corine Land Cover

“The psychological evaluation” in a chronic clinical pain: a new figure of paradoxality?

International audienc

Egypte : années 80 : éléments pour un bilan de l'"ouverture"

Bilan et réflexion sur l'expérience de planification urbaine au Caire au cours des 30 dernières années à travers l'étude des schémas directeurs de 1953, 1970 et 1981, tels sont les deux thèmes abordés par l'article. Pour chacun des 3 schémas directeurs sont analysés le contexte politique, économique et social de leur élaboration, les procédures d'élaboration, les options prises et les modalités de mise en oeuvre qui reflètent la nature de l'Etat et des alliances de classe

Contributions of the Pleiades imagery to the integrated management of coastal areas - Application to the Thau territory

At present and within a context of integrated coastal management, the population growth and increasing land pressure with their subsequent land cover changes on the Thau basin make this territory an important policy issue. In order to cope with the issues at stake the Thau regional authorities have entrusted SMBT from 2006 onwards with the joint development of several planning tools (SCoT, SAGE and Natura 2000 Convention) to conduct an integrated approach to territorial development. The aim of the present paper is to present the methodology used for mapping the initial 2012/2013 land use cover of the Thau basin from Pleiades imagery. This map will be a basic input for the observatory of the Thau territory and support the implementation of planning tools. The methodology was divided into two parts: first, a photo-interpretation approach for artificialised area mapping and evolution monitoring over several years and second, a remote sensing detection approach with the achievement of an object-oriented classification of agricultural and natural environments. This methodology allowed to obtain an up-to-date land use cover according to a 4 level typology adapted from the CORINE land cover nomenclature. This land cover will be updated every second year to help produce assessment and monitoring indicators for the Thau territory