Slctr

Efficacy and safety of oral ivermectin in the treatment of COVID-19 patients: A randomized double-blind controlled clinical trial

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SLCTR Registration Number

SLCTR/2021/020

Date of Registration

19 Jul 2021

The date of last modification

Oct 18, 2021

Application Summary

Scientific Title of Trial

Efficacy and safety of oral ivermectin in the treatment of COVID-19 patients: A randomized double-blind controlled clinical trial

Public Title of Trial

A randomized control trial to assess the efficacy and safety of ivermectin in the treatment of mild to moderate COVID 19 patients

Disease or Health Condition(s) Studied

COVID-19

Scientific Acronym

IVERCOV (Ivermectin in COVID 19)

Public Acronym

COVID-19

Brief title

Ivermectin for COVID-19

Universal Trial Number

U1111-1266-8924

Any other number(s) assigned to the trial and issuing authority

EC-21-EM02 (ERC, FM UoC)

Trial Details

What is the research question being addressed?

Is ivermectin effective and safe in the treatment of patients with mild to moderate COVID -19?

Type of study

Interventional

Study design

Allocation

Randomized controlled trial

Masking

Double blinded : Participants, Investigators, Data analysts, Healthcare providers, Outcome assessors

Control

Placebo

Assignment

Parallel

Purpose

Treatment

Study Phase

Phase 2

Intervention(s) planned

The study will be based at several COVID-19 treatment centres namely the National Institute of Infectious Diseases (NIID) commonly known as Infectious Diseases hospital-Angoda,

This is a blinded study. Neither participants, nor investigators, will be aware of treatment assignments prior to the conclusion of the study.

Computer-generated random numbers will be generated in blocks of 10 for randomization.

Either “ivermectin” tablets or placebo tablets will be packed into identical packages numbered from 1 to 400 according to the list of computer-generated random numbers.

Interventional arm will receive Ivermectin 24 mg daily for 5 days and standard care given to any other patient admitted to hospital (circular dated 02.12.20: Health.gov.lk. 2021. home. [online] Available at: http://health.gov.lk/) [duration]

Control arm will receive the same strength and weight look alike placebo tablets and standard care given to any other patient admitted to hospital (circular dated 02.12.20: Health.gov.lk. 2021. home. [online] Available at: http://health.gov.lk/) for five days.

The control arm will receive a placebo as 24mg daily for 05 days. Ingredients in the placebo include Microcrystalline Cellulose, Pregelatinised Starch,Sodium Starch, Anhydrous Citric acid, Butylated Hydroxyanisole, Pigment Blend Yellow (PB 3071), Colloid Anhydrous Silica and Magnesium Stearate

Inclusion criteria

• Patients who are over 18 years of age • Both male and female • Any patient positive for SARS 2-Corona Virus by RT-PCR tests or antigen testing using nasopharyngeal swab/aspirate within 48 hours prior to randomization and is admitted for treatment to NIID. • Cycle threshold (Ct) value <38 at the time of recruitment • Mild to moderate COVID-19 infection Mild disease: Symptoms such as fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, anosmia. Moderate disease: Symptoms of mild disease and Signs such as shortness of breath with exertion, respiratory rate >= 20 but <30/min, saturation of oxygen >93% of room air , heart rate >= 90/min but <125/min • Negative antibody test • Within 4 days of onset of symptoms and RT-PCR positivity within 48 hours in a symptomatic patient

Exclusion criteria

• Pregnancy (confirmed or suspected with a history of a missing menstrual period for more than a week) • Breast-feeding mothers • Adolescents below 18 years • HIV co-infection • Patients who are known to have allergy to ivermectin or anthelminths • Patients with severe disease as indicated by SpO2 <=93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate >=30 per minute, heart rate >=125 per minute • Patients with critical disease ie. those who require mechanical ventilation or anticipated impending need for mechanical ventilation • Those who have received the vaccine *. A patient recruited in any other trials simultaneously

Primary outcome(s)

1. 1.Reduction of viral burden (by 50%) based on the natural log Cycle threshold (Ct) value of the reverse transcriptase- quantitative PCR test (RT-PCR) for SARS-COV-2. (Specimen will be a nasopharyngeal swab or aspirate. Viral burden will be calculated using the Ct values as done in BLAZE-1 study protocol.	[ Baseline, day 06 and day 10 from the date of intervention. ]
2. 2.Clinical progression of the patient using WHO Clinical Progression Scale	[ Day 03, 06, 10, 14, 21 and 28 from the date of intervention (remote monitoring if discharged) ]
3. 3.Percentage of participants who experience side effects recorded by the patient on data sheet for assessment of symptoms and side effects.	[ Day of intervention, days 03, 06, 10 and 14 ]
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Secondary outcome(s)

1. Improvement of the symptoms by 50% by day 6 and by 100% by day 10 of intervention. Each symptom is scored by the research assistant as absent (score 0), mild (1), moderate (2) or severe (3) as used in the BLAZE-1 study. 50% improvement in treatment arm and 20% in the control arm – difference of 30%: Can detect an effect size (odds ratio) of 4.0.	[ At baseline, day 03, 06, 10, 14, 21 and 28 from the time of ingestion of the first dose (remote monitoring if discharged) ]
2. 3.50% reduction of development of hypoxia (SPO2 <94%)	[ On day 03, 06, 10 and 14 ]
3. 4.50% improvement of lymphopaenia by day 6. Lymphopaenia is defined as lymphocyte count <1.0 × 109/L.	[ On day 6 after admission. ]
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Target number/sample size

236 (118 in a group)

Countries of recruitment

Sri Lanka

Anticipated start date

2021-07-26

Anticipated end date

2022-07-26

Date of first enrollment

2021-07-29

Date of study completion

Recruitment status

Recruiting

Funding source

Self funding

Regulatory approvals

Submitted but pending reply

State of Ethics Review Approval

Status

Approved

Date of Approval

2021-07-01

Approval number

EC-21-EM02

Details of Ethics Review Committee

Name:	Ethics review committee of the Faculty of Medicine, University of Colombo.
Institutional Address:	Ethics Review Committee Faculty of Medicine University of Colombo P O Box 271, Kynsey Road, Colombo 8, Sri Lanka
Telephone:	+94-11-2695300 ext 240
Email:	ethicscommitteemfc@gmail.com

Contact & Sponsor Information

Contact person for Scientific Queries/Principal Investigator

Dr Ananda Wijewickrama
Consultant Physician
National Institute of Infectious Diseases, Mandawila road, Angoda, Sri Lanka
0112411224
077-755 9398

anandawijewickrama012@gmail.com

Contact Person for Public Queries

Dr Ananda Wijewickrama
Consultant Physician
National Institute of Infectious Diseases, Mandawila road, Angoda, Sri Lanka
0112411224
077-755 9398

Primary study sponsor/organization

Dr Ananda Wijewickrama
Consultant Physician
National Institute of Infectious Diseases, Mandawila road, Angoda, Sri Lanka
077-755 9398

anandawijewickrama012@gmail.com

Secondary study sponsor (If any)

Trial Completion details

Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

Yes

IPD sharing plan description

Study protocol and statistical analysis plan will be available on justified request only. The data will be available three months after article publication up to five years after publication. The data will be shared with investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. Data will be shared for individual participant data meta analysis. Proposals should be directed to anandawijewickrama012@gmail.com . To gain access, data requestors will need to sign a data access agreement. Data will be available for 5 years from the time of publication

Study protocol available

Yes

Protocol version and date

Protocol URL

Results summary available

Date of posting results

Date of study completion

Final sample size

Date of first publication

Link to results

Brief summary of results