Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04359953 |
| Other study ID # |
7747 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
April 25, 2020 |
| Est. completion date |
June 1, 2022 |
Study information
| Verified date |
July 2022 |
| Source |
University Hospital, Strasbourg, France |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In November 2019, Wuhan city in China, became the center of an outbreak of pneumonia due to a
novel coronavirus SARS-CoV-2, which disease was named coronavirus disease 2019 (COVID19) in
February, 2020. The COVID19 is much more dangerous for people over 60 with a death rate of
3.6% after 60, 8.0% after 70 and 14.8% after 80 -and according to our Italian colleagues over
20% after 90- against 2.3% in the general population. The elderly patients who died most
often had multiple comorbidities and in particular: cardiovascular disease (10.5% mortality),
diabetes (7.3%), chronic respiratory disease (6.3%) and hypertension (6%). These elderly
patients with COVID19 are therefore very fragile and require treatment that fights the virus
but is also adapted to their state of health and age. Most of current therapeutic trials
worldwide exclude people aged over 75 years, which is precisely the age group affected by
COVID19. We therefore propose to carry out a therapeutic trial specific to the elderly with
drugs at doses that are bearable for these patients. Using the WHO, clinicaltrial, pubmed and
the Chinese CCDC/CHCTR websites to find the better drugs adapted to elderly people, we
decided after concertation between infectiologists and geriatricians to do a four arms
clinical trial during two weeks twice a day: Hydroxychloroquine 200mg, Telmisartan 40mg,
Azithromycin 250mg and standard care. We therefore hypothesize that one or more of these
treatments may have a beneficial effect in controlling COVID19, without major and repeated
side effects in elderly patients.
Description:
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 day
- Azithromycin 250 mg twice a day
- Telmisartan 40mg twice a day
- Standard care
The 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.
