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

Phase 3

Withdrawn

• Conditions: Sars-CoV2
• Interventions: Other: Standard of care (SOC); Drug: Association of diltiazem and niclosamide; Drug: Hydroxychloroquine

• Registration Number: NCT04372082
• Lead Sponsor: University Hospital, Lille

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-04
• Study First Submitted: 2020-04-30
• Study First Submitted QC: 2020-04-30
• Study Start: 2020-05
• Study First Posted: 2020-05-01
• Last Update Submitted: 2021-03-08
• Last Update Posted: 2021-03-11
• Primary Completion: 2023-05
• Study Completion: 2023-05

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SOC + Diltiazem-Niclosamide	Standard of care (SOC)	-
SOC + Hydroxychloroquine	Standard of care (SOC)	-
SOC + Diltiazem-Niclosamide	Association of diltiazem and niclosamide	-
standard of care (SOC)	Standard of care (SOC)	-
SOC + Hydroxychloroquine	Hydroxychloroquine	-

Primary Outcome Measures

Name	Time	Method
Assisted-ventilation and/or hospitalization (composite criteria)	At day 14
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
death	At day 14	Composite criteria

Secondary Outcome Measures

Name	Time	Method
adverse drug reactions	during study, up to 28 days
cumulative incidence of hospitalizations	at day 14
cumulative incidence of viral shedding on SARS-CoV-2 rt-PCR on nasopharyngeal swab;	at day 3, day 8
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
cumulative incidence of the use of oxygen therapy, non-invasive ventilation or invasive ventilation ( composite criteria)	at day 14
Mortality	at day 14 and at day 28	Number of patients death