Clinical trial NCT04438850: COVidIVERmectin: Ivermectin for Treatment of Covid-19
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Covid19
Keywords: ivermectin
Lead sponsor: IRCCS Sacro Cuore Don Calabria di Negrar
Sponsor class: OTHER
Collaborators: name: Istituto Di Ricerche Farmacologiche Mario Negri
First posted: 2020-06-19
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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:

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.

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

Primary outcomes:
measure: SADR
timeFrame: 14 days
measure: Viral load
timeFrame: Assessed at day 7
Secondary outcomes:
measure: Trend viral load
timeFrame: Days 7 and 14 from baseline
measure: Clinical resolution
timeFrame: Assessed on Day 30
measure: Viral clearance
timeFrame: assessed on days 14 and 30
measure: Virological clearance
timeFrame: Assessed at day 14 and 30
measure: hospitalization rate
timeFrame: Day 30
measure: Severity score
timeFrame: Assessed at Day 14 and Day 30
Other outcomes:
Locations:
city: Negrar
country: Italy
facility: IRCCS Sacro Cuore Don Calabria hospital
state: Verona
city: Bologna
country: Italy
facility: Policlinico S. Orsola
city: Milan
country: Italy
facility: Ospedale Luigi Sacco
city: Rovereto
country: Italy
facility: Ospedale di Rovereto
city: Turin
country: Italy
facility: Ospedale Amedeo di Savoia
Study officials:
affiliation: IRCCS Sacro Cuore Don Calabria hospital
name: Zeno Bisoffi
role: PRINCIPAL_INVESTIGATOR
References: