Sars-CoV2
Conditions
Keywords
Covid-19, Hydroxychloroquine, Dilitazem, Niclosamide
Brief summary
No optimal antiviral intervention has been yet validated to treat COVID-19 disease. Comorbidities, such as older age, obesity, diabetes, history of cardiovascular diseases are associated with poor prognosis. This study aims to evaluate the efficacy of two experimental antiviral treatments, compared to standard of care (SOC), to prevent clinical worsening, hospitalization or death at day 14 in adults with documented SARS-CoV-2 infection, asymptomatic or with symptoms lasting less than 8 days, and associated comorbidities without any severity criteria of the disease at inclusion. Participants will be randomized to receive SOC alone or SOC + hydroxychloroquine 200 mg three times a day during 10 days or SOC + association of niclosamide 2 g at J1 then 500 mg two times a day with diltiazem 60 mg three times a day during 10 days. Efficacy and tolerance of each treatments will be compared across the three treatment groups during the 28 days of follow-up.
Interventions
OTHERStandard of care (SOC)
SOC procedures including self-monitoring and medical follow-up of clinical signs and if necessary any other symptomatic treatment (paracetamol, antibiotics, steroids, oxygen…) during the whole study duration
DRUGHydroxychloroquine
200 mg x 3 per day during 10 days in addition to SOC
DRUGAssociation of diltiazem and niclosamide
niclosamide 500 mg x 4 at J1 then 500 mg x 2 per day + diltiazem 60 mg x 3 per day during 10 days in addition to SOC
Sponsors
I-site University Lille North Europe
University Hospital, Lille
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive SARS-CoV-2 test on nasopharyngeal swab * Onset of symptoms \<8 days prior to randomization * NEWS score\<4 AND no item ≥2 * At least one comorbidity among: age ≥ 70 years old, history of cardiac disease, diabetes, obesity, chronic kidney disease, chronic respiratory failure, immunosuppression, neoplasia, liver failure (stage ≥ Child-Pugh B) * Fully able to understand the challenges of the trial * Signed informed consent * Covered by Health Insurance
Exclusion criteria
For all patients: * Inability to decide to participate * Pregnancy or breath feeding * Hypersensitivity to any of the test drugs * stage 4 or 5 chronic kidney disease (DFG \<30 mL/min/1.73 m²) For hydroxychloroquine arm: * Long QT syndrome or QTc space \>500 ms * Treatment with piperazine, halofantrine, dasatinib, nilotinib, citalopram, escitalopram, hydroxyzine, domperidone * Hepatic porphyria, retinopathy, known glucose-6-phosphate dehydrogenase deficiency, * Heart rate \<50/min * hypokaliemia \< 3.5 mmol/L For diltiazem arm: * Heart rate\<40/min * Sinus bradycardia, second- or third-degree atrioventricular block * Left heart insufficiency with pulmonary stasis * Treatment with dantrolene, pimozide, dihydroergotamine, ergotamine, nifedipine, ivabradine, esmolol, bêta-blockers (bisoprolol, carvedilol, metoprolol, nebivolol), fingolimod
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| death | At day 14 | Composite criteria |
| clinical worsening (composite criteria) | At day 14 | clinical worsening defined by at least one of the NEWS score item \> 2 (temperature \>39,1°C or\<35°C, cardiac rate \>111 or ≤40 bpm, respiratory rate \> 21 or ≤8 cycles par minute, SaO2 ≤ 93% room air (if its measure is available),need of oxygen |
| Assisted-ventilation and/or hospitalization (composite criteria) | At day 14 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | at day 14 and at day 28 | Number of patients death |
| National Early Warning Score (NEWS) | at day 3, day 8, day 14 day 28 | clinical state as reflected by NEWS scoring, the clinical state of the patient regarding respiratory state as defined by the NEWS scoring system |
| adverse drug reactions | during study, up to 28 days | — |
| cumulative incidence of viral shedding on SARS-CoV-2 rt-PCR on nasopharyngeal swab; | at day 3, day 8 | — |
| cumulative incidence of hospitalizations | at day 14 | — |
| cumulative incidence of the use of oxygen therapy, non-invasive ventilation or invasive ventilation ( composite criteria) | at day 14 | — |
Outcome results
None listed