Hydroxychloroquine or Diltiazem-Niclosamide for the Treatment of COVID-19

Sars-CoV2 Clinical Trial

— HYdILIC  

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04372082
• Other study ID #: 2020_40
• Secondary ID: 2020-002188-72
• Status: Withdrawn
• Phase: Phase 3
• Start date: May 2020
• Est. completion date: May 2023

Study information

• Verified date: April 2020
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sars-CoV2

Intervention

Other:
• Standard 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

Drug:
• Hydroxychloroquine
200 mg x 3 per day during 10 days in addition to SOC
• Association 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	I-site University Lille North Europe

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	death	Composite criteria	At day 14
Primary	clinical worsening (composite criteria)	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	At day 14
Primary	Assisted-ventilation and/or hospitalization (composite criteria)		At day 14
Secondary	National Early Warning Score (NEWS)	clinical state as reflected by NEWS scoring, the clinical state of the patient regarding respiratory state as defined by the NEWS scoring system	at day 3, day 8, day 14 day 28
Secondary	cumulative incidence of hospitalizations		at day 14
Secondary	cumulative incidence of the use of oxygen therapy, non-invasive ventilation or invasive ventilation ( composite criteria)		at day 14
Secondary	Mortality	Number of patients death	at day 14 and at day 28
Secondary	cumulative incidence of viral shedding on SARS-CoV-2 rt-PCR on nasopharyngeal swab;		at day 3, day 8
Secondary	adverse drug reactions		during study, up to 28 days