COVidIVERmectin: Ivermectin for Treatment of Covid-19 (COVER)
Primary Purpose
Covid19
Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Ivermectin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring ivermectin
Eligibility 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
Sites / Locations
- IRCCS Sacro Cuore Don Calabria hospital
- Policlinico S. Orsola
- Ospedale Luigi Sacco
- Ospedale di Rovereto
- Ospedale Amedeo di Savoia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
I_600
I_1200
Placebo
Arm Description
ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo
ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days
placebo
Outcomes
Primary Outcome Measures
SADR
Number of serious adverse drug reaction
Viral load
Quantitative viral load as measured by quantitative, digital droplet PCR.
Secondary Outcome Measures
Trend viral load
1. Trend over time of quantitative viral load at Day 7 and 14 as measured by quantitative, digital droplet PCR.
Clinical resolution
Time to clinical resolution (for symptomatic patients).
Viral clearance
Time from diagnosis to documented viral clearance
Virological clearance
Proportion of patients with virological clearance
hospitalization rate
rate of hospitalization
Severity score
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
Full Information
NCT ID
NCT04438850
First Posted
April 10, 2020
Last Updated
June 17, 2021
Sponsor
IRCCS Sacro Cuore Don Calabria di Negrar
Collaborators
Istituto Di Ricerche Farmacologiche Mario Negri
1. Study Identification
Unique Protocol Identification Number
NCT04438850
Brief Title
COVidIVERmectin: Ivermectin for Treatment of Covid-19
Acronym
COVER
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
Incidence has dramatically dropped and there is lack of eligible patients
Study Start Date
July 31, 2020 (Actual)
Primary Completion Date
June 8, 2021 (Actual)
Study Completion Date
June 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IRCCS Sacro Cuore Don Calabria di Negrar
Collaborators
Istituto Di Ricerche Farmacologiche Mario Negri
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
Primary objectives
The study is aimed:
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,
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
the temporal profile of viral load at baseline, day 7, 14 and 30
the time to clinical cure (for symptomatic patients)
the proportion of patients with virological clearance at day 14 and 30.
the hospitalization rate.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
ivermectin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
93 (Actual)
8. Arms, Groups, and Interventions
Arm Title
I_600
Arm Type
Experimental
Arm Description
ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo
Arm Title
I_1200
Arm Type
Experimental
Arm Description
ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo
Intervention Type
Drug
Intervention Name(s)
Ivermectin
Other Intervention Name(s)
Ivermectin 9 mg cp by Chemo group
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo supplied by chemo group
Intervention Description
Patients should take placebo orally on an empty stomach with water
Primary Outcome Measure Information:
Title
SADR
Description
Number of serious adverse drug reaction
Time Frame
14 days
Title
Viral load
Description
Quantitative viral load as measured by quantitative, digital droplet PCR.
Time Frame
Assessed at day 7
Secondary Outcome Measure Information:
Title
Trend viral load
Description
1. Trend over time of quantitative viral load at Day 7 and 14 as measured by quantitative, digital droplet PCR.
Time Frame
Days 7 and 14 from baseline
Title
Clinical resolution
Description
Time to clinical resolution (for symptomatic patients).
Time Frame
Assessed on Day 30
Title
Viral clearance
Description
Time from diagnosis to documented viral clearance
Time Frame
assessed on days 14 and 30
Title
Virological clearance
Description
Proportion of patients with virological clearance
Time Frame
Assessed at day 14 and 30
Title
hospitalization rate
Description
rate of hospitalization
Time Frame
Day 30
Title
Severity score
Description
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
Time Frame
Assessed at Day 14 and Day 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zeno Bisoffi
Organizational Affiliation
IRCCS Sacro Cuore Don Calabria hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS Sacro Cuore Don Calabria hospital
City
Negrar
State/Province
Verona
ZIP/Postal Code
37024
Country
Italy
Facility Name
Policlinico S. Orsola
City
Bologna
Country
Italy
Facility Name
Ospedale Luigi Sacco
City
Milan
Country
Italy
Facility Name
Ospedale di Rovereto
City
Rovereto
Country
Italy
Facility Name
Ospedale Amedeo di Savoia
City
Turin
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The anonymized database will be uploaded into a public repository
IPD Sharing Time Frame
The database will be available upon publication of the results
IPD Sharing Access Criteria
The data will be available in a public repository
Learn more about this trial
COVidIVERmectin: Ivermectin for Treatment of Covid-19
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