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

NCT04372082 | Withdrawn Phase 3 DMC

• 2 other identifiers: 2020_402020-002188-72
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Sars-CoV2

Keywords

Covid-19; Hydroxychloroquine; Dilitazem; Niclosamide

Outcome Measures

Primary Outcomes (3)

• death

  Composite criteria

  At day 14

• 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

• Assisted-ventilation and/or hospitalization (composite criteria)

  At day 14

Secondary Outcomes (6)

• National Early Warning Score (NEWS)

  at day 3, day 8, day 14 day 28

• 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

• Mortality

  at day 14 and at day 28

• cumulative incidence of viral shedding on SARS-CoV-2 rt-PCR on nasopharyngeal swab;

  at day 3, day 8

Study Arms (3)

standard of care (SOC)

PLACEBO COMPARATOR

Other: Standard of care (SOC)

SOC + Hydroxychloroquine

EXPERIMENTAL

Other: Standard of care (SOC); Drug: Hydroxychloroquine

SOC + Diltiazem-Niclosamide

EXPERIMENTAL

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

Interventions

Standard of care (SOC) OTHER

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

SOC + Diltiazem-Niclosamide; SOC + Hydroxychloroquine; standard of care (SOC)

Hydroxychloroquine DRUG

200 mg x 3 per day during 10 days in addition to SOC

SOC + Hydroxychloroquine

Association of diltiazem and niclosamide DRUG

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

SOC + Diltiazem-Niclosamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Lille: lead
• I-site University Lille North Europe: collaborator

MeSH Terms

Conditions

COVID-19

Interventions

Standard of Care; Hydroxychloroquine; Niclosamide

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Salicylanilides; Anilides; Amides; Organic Chemicals; Salicylamides; Aniline Compounds; Amines

Study Officials

• Karine Faure, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 1, 2020
• Study Start: May 1, 2020
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: March 11, 2021

Record last verified: 2020-04