Efficacy of Hydroxychloroquine, Telmisartan and Azithromycin on the Survival of Hospitalized Elderly Patients With COVID-19 : Efficacy of Hydroxychloroquine, Telmisartan and Azithromycin on the Survival of Hospitalized Elderly Patients With COVID-19: a Randomized, Multicenter, Adaptative Study

In the absence of a validated treatment, any patient over 75 years -or demented above 60- of age arriving in one of our hospital centres with a COVID19 infection objectified by RT-PCR will be offered this therapeutic trial. Patients will be randomized. During their hospitalization, they will be closely monitored clinically. It means daily evaluation of temperature, pulse, respiratory rate, blood pressure, need for oxygen therapy and general clinical examination. The lung severity scale and WHO scale will be done daily. Any side effects of any kind, in particular serious side effects will be reported within 24 hours on the electronic CRF. RT-PCR with search for SARS-Cov-2 will be evaluated at D0, D7 and D14. A blood sample will be taken at D0, D7 and D14 with blood count, CRP and biobanking. Functional scales (ADL, confusion scale, walking) will be evaluated every 3 days. If death occurs, the precise circumstances and time of death will be transmitted, as well as the precise origin of death: only COVID19 or other associated disease (bacterial infection, heart failure, kidney failure, etc...).Symptomatic treatment will be at the discretion of the clinician, but will be recorded in the eCRF, particularly in relation to the use of corticosteroids or other immunomodulators.The study will consist of 1600 patients over 75 years of age (or above 60 demented) with COVID19 requiring hospitalization, equally divided into four groups with the following treatment during two weeks for each arm:Hydroxychloroquine 200mg twice a dayAzithromycin 250 mg twice a dayTelmisartan 40mg twice a dayStandard careThe choice of these three drugs was done considering the benefit-risk balance, i.e. by choosing drugs with few side effects but high potential for elderly people (including severe renal insufficiency). Hydroxychloroquine was chosen because 1. This drug was demonstrated to be potent and more potent than Chloroquine at inhibiting SARS-CoV-2 in vitro. An unpublished clinical trial with 100 patients showing superiority of chloroquine compared to placebo with improvement of lung image findings, promotion a virus-negative conversion and shortening the disease course . An open-label non randomized clinical trial with 42 patients showing a faster reduction of the virus in the Hydroxychloroquine treated group. Azithromycin was associated in the previous trial with Hydroxychloroquine with positive results on RT-PCR. Recently bioinformatic analysis conclude to SARS-CoV-2 protease inhibition with Macrolides. Moreover macrolides are known to have immunomodulatory effects, which could be of interest in the context of hyperinflammation. Telmisartan is an angiotensin 2 AT1 receptor antagonist. COVID19 use ACE2 as a receptor, a modulator of the activity of different angiotensin. The COVID19-ACE2 interaction increases the activity of angiotensin and thus increases the activity of the AT1 receptor, that results in increased pulmonary vascular permeability and therefore contributes to lung injury. Thus Telmisartan could be a protector against lung injury due to Sars-Cov-2, inhibiting AT1 receptor.The expected benefits are multiple thanks to this original project:1. There is a research emergency. No drug has been shown to be really effective against COVID19 and even less in the elderly, so therapeutic trials are needed.2. If one of these 3 drugs turns out to be positive, it could even be taken at a very early stage, for example as a result of a recent contagion, in elderly population at high risk of death.3. If one of the three treatments was positive, the cost-effectiveness would be very favorable compared to other treatments currently being tested. This could benefit a larger population, particularly in developing countries where COVID19 is arriving.4. This trial will be evolutionary, i.e. we will be able to add a treatment arm if a new molecule that is potentially effective in the elderly appears..

Medienart:	Klinische Studie

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	ClinicalTrials.gov - (2022) vom: 11. Juli Zur Gesamtaufnahme - year:2022

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 COVID-19 Medical Condition: COVID-19 Infection Phase: Phase 3 Recruitment Status: Terminated Study Type: Interventional

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: April 24, 2020, Last downloaded: ClinicalTrials.gov processed this data on July 18, 2022, Last updated: July 20, 2022

Study ID:	NCT04359953 7747
Veröffentlichungen zur Studie:

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PPN (Katalog-ID):	CTG003370003