Ivermectin for Severe COVID-19 Management

Afyonkarahisar Health Sciences University

Status and phase: Completed; Phase 3

Conditions: COVID-19

Treatments: Drug: Ivermectin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04646109

IVMC_03

Details and patient eligibility

About

In this multicenter study; it was aimed to investigate the effectiveness and safety of ivermectin use in the treatment of patients with severe COVID-19 pneumonia that have no mutations which alter ivermectin metabolism and cause side effects.

Full description

Patients with severe COVID-19 pneumonia were included in the study. Two groups, the study group and the control group, took part in the study.

Ivermectin 200 mcg/kg/day for five days (9 mg between 36-50 kg, 12 mg between 51-65 kg, 15 mg between 66-79 kg and 200 microgram/kg in > 80 kg) in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine (2x400mg loading dose followed by 2x200mg, po, 5 days) + favipiravir (2x1600mg loading dose followed by 2x600mg maintenance dose, po, total 5 days) + azithromycin (first day 500mg followed by 4 days 250mg/day, po, total 5 days)- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin.

The mutations in 29 pairs of primers in mdr1/abcab1 gene by sequencing analysis using Sanger method, and the haplotypes and mutations of the CYP3A4 gene that cause the function losing were investigated among the patients who meet criteria and who were included in the study group according to randomization. Mutation screening was done when the first dose of the research drug ivermectin was given, ivermectin treatment was not continued in patients with mutations detected as a result of genetic examination and these patients were excluded from the study.

Patients were followed for 5 additional days after treatment. At the end of the treatment and follow-up period (At the end of 10th day), clinical response and changes in oxygenation and laboratory parameters were evaluated.

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients who were hospitalised with a pre-diagnosis of "severe COVID-19 pneumonia" and thereafter diagnosis of COVID-19 was also confirmed microbiologically with PCR positivity in respiratory tract samples were included into the study. They were randomized to the study and control group, respectively.

Patients with at least one of the criteria below were accepted as patients with severe COVID-19 pneumonia;

1. Presence of tachypnea ≥ 30/minute, SpO2 level < 90% in room air, PaO2/FiO2 <300 in oxygen receiving patient
2. Presence of specific radiological finding for COVID-19 in lung tomography (bilateral lobular, peripherally located, diffuse patchy ground glass opacities)
3. Mechanical ventilation requirement
4. Acute organ dysfunction findings; patients with SOFA (sepsis-related organ failure assessment) score >2

Exclusion criteria

• Patients with the following characteristics were excluded from the study.

  1. Pediatric patients; <18 years of old
  2. Patients with chronic liver or kidney disease
  3. Pregnant women
  4. Patients with known ivermectin allergy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 2 patient groups

Control Group

No Intervention group

Description:

Patients who were hospitalised with a pre-diagnosis of severe COVID-19 pneumonia and thereafter diagnosis of COVID-19 was also confirmed microbiologically with PCR positivity in respiratory tract samples were included into the study. They were randomized to the control and study group, respectively. Hydroxychloroquine, favipiravir and azithromycin (HFA) standard treatment protocol were given to the control group as recommended in the "COVID-19 (SARS-CoV-2 Infection) Guide" prepared by the Republic of Turkey Ministry of Health.

Study Group

Experimental group

Description:

In addition to HFA treatment, ivermectin 200 micrograms/kg/day (9mg between 36-50 kg, 12mg between 51-65 kg, 15mg between 66-79 kg and 200 micrograms/kg in \> 80 kg) in the form of a solution prepared for enteral use was added (HFA+I) to the treatment protocol of the study group's for five days. Blood sample was taken with the first dose of ivermectin and haplotype analysis was performed in ABCB1 and CYP3A4 genes in the whole study group.

Treatment:

Drug: Ivermectin