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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04372082
Recruitment Status : Not yet recruiting
First Posted : May 1, 2020
Last Update Posted : May 1, 2020
Sponsor:
Collaborator:
I-site University Lille North Europe
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Sars-CoV2 Other: Standard of care (SOC) Drug: Hydroxychloroquine Drug: Association of diltiazem and niclosamide Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
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
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023


Arm Intervention/treatment
Placebo Comparator: standard of care (SOC) 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

Experimental: SOC + Hydroxychloroquine 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

Experimental: SOC + Diltiazem-Niclosamide 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: 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




Primary Outcome Measures :
  1. death [ Time Frame: At day 14 ]
    Composite criteria

  2. clinical worsening (composite criteria) [ Time Frame: 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

  3. Assisted-ventilation and/or hospitalization (composite criteria) [ Time Frame: At day 14 ]

Secondary Outcome Measures :
  1. National Early Warning Score (NEWS) [ Time Frame: 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

  2. cumulative incidence of hospitalizations [ Time Frame: at day 14 ]
  3. cumulative incidence of the use of oxygen therapy, non-invasive ventilation or invasive ventilation ( composite criteria) [ Time Frame: at day 14 ]
  4. Mortality [ Time Frame: at day 14 and at day 28 ]
    Number of patients death

  5. cumulative incidence of viral shedding on SARS-CoV-2 rt-PCR on nasopharyngeal swab; [ Time Frame: at day 3, day 8 ]
  6. adverse drug reactions [ Time Frame: during study, up to 28 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04372082


Contacts
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Contact: Karine Faure, MD,PhD 0320445962 ext +33 karine.faure@chru-lille.fr

Sponsors and Collaborators
University Hospital, Lille
I-site University Lille North Europe
Investigators
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Principal Investigator: Karine Faure, MD,PhD University Hospital, Lille
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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT04372082    
Other Study ID Numbers: 2020_40
2020-002188-72 ( EudraCT Number )
First Posted: May 1, 2020    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Lille:
Covid-19
Hydroxychloroquine
Dilitazem
Niclosamide
Additional relevant MeSH terms:
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Hydroxychloroquine
Niclosamide
Diltiazem
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Anticestodal Agents
Antiplatyhelmintic Agents
Anthelmintics
Antinematodal Agents