Ivermectin for Severe COVID-19 Management

NCT ID: NCT04646109

Last Updated: 2021-01-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-11

Study Completion Date

2020-09-02

Brief Summary

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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.

Detailed Description

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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.

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients who were hospitalised with a pre-diagnosis of severe COVID-19 pneumonia and thereafter diagnosis of COVID-19 was also confirmed microbiologically with polymerase chain reaction (PCR) positivity in respiratory tract samples were included into the study. They were randomized to the study and control group, respectively. Single numbered patients were accepted as study group and double numbered patients as control group
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Control Group

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Study Group

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.

Group Type EXPERIMENTAL

Ivermectin

Intervention Type DRUG

Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions.

Interventions

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Ivermectin

Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions.

Intervention Type DRUG

Other Intervention Names

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Hydroxychloroquine, favipiravir and azithromycin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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NeuTec Pharma

INDUSTRY

Sponsor Role collaborator

Afyonkarahisar Health Sciences University

OTHER

Sponsor Role lead

Responsible Party

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Nurullah Okumuş

Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nurullah Okumuş, Prof. Dr.

Role: STUDY_CHAIR

Afyonkarahisar Health Science University, Afyonkarahisar, Turkey

Neşe Demirtürk, A. Prof. Dr.

Role: STUDY_DIRECTOR

Afyonkarahisar Health Science University, Afyonkarahisar, Turkey

Rıza A. Çetinkaya, Prof. Dr.

Role: STUDY_DIRECTOR

Haydarpasa Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey

Rahmet Güner, Prof. Dr.

Role: STUDY_DIRECTOR

Yıldırım Beyazıt University, Ankara City Hospital, Ankara, Turkey

İsmail Y. Avcı

Role: STUDY_DIRECTOR

Gulhane Faculty of Medicine, University of Health Sciences, Ankara, Turkey

Locations

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Afyonkarahisar Health Science University

Afyonkarahisar, , Turkey (Türkiye)

Site Status

Gulhane Faculty of Medicine, University of Health Sciences

Ankara, , Turkey (Türkiye)

Site Status

Yıldırım Beyazıt University, Ankara City Hospital

Ankara, , Turkey (Türkiye)

Site Status

Haydarpasa Sultan Abdulhamid Han Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

Reference Type BACKGROUND
PMID: 32109013 (View on PubMed)

Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J Microbiol Immunol Infect. 2020 Jun;53(3):436-443. doi: 10.1016/j.jmii.2020.03.034. Epub 2020 Apr 4.

Reference Type BACKGROUND
PMID: 32307245 (View on PubMed)

Croci R, Bottaro E, Chan KW, Watanabe S, Pezzullo M, Mastrangelo E, Nastruzzi C. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin. Int J Biomater. 2016;2016:8043983. doi: 10.1155/2016/8043983. Epub 2016 May 8.

Reference Type BACKGROUND
PMID: 27242902 (View on PubMed)

Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020 Sep;73(9):593-602. doi: 10.1038/s41429-020-0336-z. Epub 2020 Jun 12.

Reference Type BACKGROUND
PMID: 32533071 (View on PubMed)

Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787. doi: 10.1016/j.antiviral.2020.104787. Epub 2020 Apr 3.

Reference Type BACKGROUND
PMID: 32251768 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://covid19.who.int/

World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard

Other Identifiers

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IVMC_03

Identifier Type: -

Identifier Source: org_study_id

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