Clinical trial NCT04372082: Hydroxychloroquine or Diltiazem-Niclosamide for the Treatment of COVID-19
Official title: Efficacy of HYdroxychloroquine and DILtiazem-nIClosamide Combination for the Treatment of Non-severe Forms of SARS-CoV2 Infection in Patients With Co-morbidities: Multicenter, Randomized, Open-labeled Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Sars-CoV2
Keywords: Covid-19
Hydroxychloroquine
Dilitazem
Niclosamide
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: I-site University Lille North Europe
First posted: 2020-05-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: death
timeFrame: At day 14
measure: clinical worsening (composite criteria)
timeFrame: At day 14
measure: Assisted-ventilation and/or hospitalization (composite criteria)
timeFrame: At day 14
Secondary outcomes:
measure: National Early Warning Score (NEWS)
timeFrame: at day 3, day 8, day 14 day 28
measure: cumulative incidence of hospitalizations
timeFrame: at day 14
measure: cumulative incidence of the use of oxygen therapy, non-invasive ventilation or invasive ventilation ( composite criteria)
timeFrame: at day 14
measure: Mortality
timeFrame: at day 14 and at day 28
measure: cumulative incidence of viral shedding on SARS-CoV-2 rt-PCR on nasopharyngeal swab;
timeFrame: at day 3, day 8
measure: adverse drug reactions
timeFrame: during study, up to 28 days
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital, Lille
name: Karine Faure, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: