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COVidIVERmectin: Ivermectin for Treatment of Covid-19 (COVER)

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: NCT04438850
Recruitment Status : Not yet recruiting
First Posted : June 19, 2020
Last Update Posted : June 19, 2020
Sponsor:
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Information provided by (Responsible Party):
IRCCS Sacro Cuore Don Calabria di Negrar

Brief Summary:

Prospective, multi-centre, randomized, double-blind trial to assess efficacy and safety of ivermectin for the treatment of initial infection with SARS-CoV2 infection.

Study arms: A) placebo B) ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo. C) ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days (I_1200). Patients will be randomized at emergency room of hospitals as well as at outpatient ambulatory care as well as at home, according to routine procedures of recruiting centres.

In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C.


Condition or disease Intervention/treatment Phase
Covid19 Drug: Ivermectin Other: Placebo Phase 2

Detailed Description:

Primary objectives

The study is aimed:

  1. at defining if ivermectin, administered at dosage of 600 μg/kg or 1200 μg/kg QD for five consecutive days is safe in patients with initial, asymptomatic or oligosymptomatic SARS_CoV-2 infection,
  2. at defining if ivermectin, administered at the dosage(s) found to be safe decreases the viral load of SARS-CoV-2 at Day 7.

Secondary objectives To assess

  1. the temporal profile of viral load at baseline, day 7, 14 and 30
  2. the time to clinical cure (for symptomatic patients)
  3. the proportion of patients with virological clearance at day 14 and 30.
  4. the hospitalization rate.
  5. the COVID-19 Severity Score at day 14 and 30

STUDY DESIGN

This is a multicentre, prospective, randomized, double-blind, adaptive phase II dose finding study.

Patients meeting the inclusion criteria will be asked to participate to the study and randomized in a 1:1:1 ratio to either:

  • Placebo arm (arm A): placebo will be identical in appearance to ivermectin in order to preserve blinding and will be administered p.o. at empty stomach with water once daily, for 5 days
  • Intervention arms: a) Ivermectin, single dose 600 μg/kg, for 5 days (I_600) and placebo (arm B) ; b) Ivermectin, single dose 1200 μg/kg, for 5 days (I_1200) (arm C) ); these drugs will be administered p.o. once daily, for 5 days.

In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C.

Patients will be randomized by a centralized computer system. At randomization a treatment ID is assigned to the patient. Once a treatment ID is assigned this must not be re-assigned even in cases of errors.

Enrolled subjects will be identified by a unique subject number (patient code) that will remain consistent for the duration of the study.

Patients will be recruited at the emergency room of hospitals, and/or among asymptomatic hospital workers found positive for SARS-CoV-2 at routine screening and/or in outpatient ambulatory settings, and/or at home, if not meeting the clinical criteria for hospitalization, according to the routine procedure of each participating site. The expected duration of subject inclusion in the study is of 1 month, or until the planned number of subjects to be enrolled will be reached.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Ivermectin and placebo treatment will be double blinded, i.e. the treatment will be unknown to both the subject and the treating physician. The hospital pharmacist will be unblinded to study treatment because in charge to prepare the study treatment according to randomization arm.
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Multi Centre Phase II, Proof of Concept, Dose Finding Clinical Trial on Ivermectin for the Early Treatment of COVID-19
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ivermectin

Arm Intervention/treatment
Experimental: I_600
ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo
Drug: Ivermectin
Patients will be administered a single oral daily dose of approximately 600 μg/Kg (486-679 μg/Kg as rounded to a whole number of tablets), or 1200 μg/Kg (1098-1286 μg/Kg).
Other Name: Ivermectin 9 mg cp by Chemo group

Experimental: I_1200
ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days
Drug: Ivermectin
Patients will be administered a single oral daily dose of approximately 600 μg/Kg (486-679 μg/Kg as rounded to a whole number of tablets), or 1200 μg/Kg (1098-1286 μg/Kg).
Other Name: Ivermectin 9 mg cp by Chemo group

Placebo Comparator: Placebo
placebo
Other: Placebo
Patients should take placebo orally on an empty stomach with water
Other Name: Placebo supplied by chemo group




Primary Outcome Measures :
  1. SADR [ Time Frame: 14 days ]
    Number of serious adverse drug reaction

  2. Viral load [ Time Frame: Assessed at day 7 ]
    Quantitative viral load as measured by quantitative, digital droplet PCR.


Secondary Outcome Measures :
  1. Trend viral load [ Time Frame: Days 7 and 14 from baseline ]
    1. Trend over time of quantitative viral load at Day 7 and 14 as measured by quantitative, digital droplet PCR.

  2. Clinical resolution [ Time Frame: Assessed on Day 30 ]
    Time to clinical resolution (for symptomatic patients).

  3. Viral clearance [ Time Frame: assessed on days 14 and 30 ]
    Time from diagnosis to documented viral clearance

  4. Virological clearance [ Time Frame: Assessed at day 14 and 30 ]
    Proportion of patients with virological clearance

  5. hospitalization rate [ Time Frame: Day 30 ]
    rate of hospitalization

  6. Severity score [ Time Frame: Assessed at Day 14 and Day 30 ]
    COVID-19 Severity Score (Coronavirus Diseases 19 Severity Score) - min value 1 ("no limitation of activities), max value 8 ("death"). Higher scores mean worse outcome



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:

  • Age >=18 years
  • Positivity at RT-PCR per SARS_CoV2 (nasopharyngeal swabs)
  • Consent to participation to the study and to the processing of personal data
  • COVID-19 Severity Score < 3
  • Patient able to take oral drugs

Exclusion Criteria:

  • Pregnant or lactating women (pregnancy test not required, if doubt patient is excluded)
  • Subjects suffering from known CNS diseases
  • Lack of (or inability to provide) informed consent
  • Patient under dialysis
  • Any severe medical condition with a prognosis of < 6 months
  • Patients under warfarin treatment
  • Patients under antiviral treatment
  • Patients under chloroquine phosphate or hydroxychloroquine

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): NCT04438850


Contacts
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Contact: Zeno Bisoffi, PhD +390456013326 zeno.bisoffi@sacrocuore.it

Locations
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Italy
IRCCS Sacro Cuore Don Calabria hospital
Negrar, Verona, Italy, 37024
Contact: Dora Buonfrate       dora.buonfrate@sacrocuore.it   
Principal Investigator: Zeno Bisoffi         
Sub-Investigator: Dora Buonfrate         
Policlinico S. Orsola
Bologna, Italy
Contact: Luciano Attard         
Ospedale Luigi Sacco
Milan, Italy
Contact: Spinello Antinori         
Ospedale di Rovereto
Rovereto, Italy
Contact: Giovanni Pedrotti         
Ospedale Amedeo di Savoia
Turin, Italy
Contact: Guido Celleri         
Spain
Hospital Clinic/ISGlobal
Barcelona, Spain
Contact: José Muñoz         
Hospital La Paz-Carlos III
Madrid, Spain
Sponsors and Collaborators
IRCCS Sacro Cuore Don Calabria di Negrar
Istituto Di Ricerche Farmacologiche Mario Negri
Investigators
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Principal Investigator: Zeno Bisoffi IRCCS Sacro Cuore Don Calabria hospital
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Responsible Party: IRCCS Sacro Cuore Don Calabria di Negrar
ClinicalTrials.gov Identifier: NCT04438850    
Other Study ID Numbers: cover_1
First Posted: June 19, 2020    Key Record Dates
Last Update Posted: June 19, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The anonymized database will be uploaded into a public repository
Supporting Materials: Study Protocol
Time Frame: The database will be available upon publication of the results
Access Criteria: The data will be available in a public repository

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by IRCCS Sacro Cuore Don Calabria di Negrar:
ivermectin
Additional relevant MeSH terms:
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Ivermectin
Antiparasitic Agents
Anti-Infective Agents