Hydroxychloroquine or Diltiazem-Niclosamide for the Treatment of COVID-19 (HYdILIC)

University Hospital, Lille

Status and phase: Withdrawn; Phase 3

Conditions: Sars-CoV2

Treatments: Drug: Hydroxychloroquine; Other: Standard of care (SOC); Drug: Association of diltiazem and niclosamide

Study type: Interventional

Funder types: Other

Identifiers

NCT04372082

2020-002188-72 (EudraCT Number)

2020_40

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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0 participants in 3 patient groups, including a placebo group

standard of care (SOC)

Placebo Comparator group

Treatment:

Other: Standard of care (SOC)

SOC + Hydroxychloroquine

Experimental group

Treatment:

Drug: Hydroxychloroquine

Other: Standard of care (SOC)

SOC + Diltiazem-Niclosamide

Experimental group

Treatment:

Other: Standard of care (SOC)

Drug: Association of diltiazem and niclosamide