A Study of the Effectiveness of an Off Label Mefloquine Use for the Treatment of Patients With COVID19

An Open Randomized Study of the Effectiveness of the Drug Mefloquine, Tablets 250 mg, Produced by FSUE SPC "Farmzashita" of the Federal Medical Biological Agency, FMBA of Russia (Russia) for the Treatment of Patients With COVID19

Study of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE "SPC" Farmzaschita " FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the "off-label" mode, to make a decision on the possibility of expanding the indications for use.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Viral; Respiratory Failure
• Intervention / Treatment: Drug: Mefloquine; Drug: Hydroxychloroquine; Combination product: Mefloquine + azithromycin + / - tocilizumab; Combination product: Hydroxychloroquine + azithromycin + / - tocilizumab

Detailed Description

Purpose of the study:

Study of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE "SPC" farmzaschita " FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the "off-label" mode, to make a decision on the possibility of expanding the indications for use.

Study aims:

1. To study the efficacy of the drug Mefloquine, tablet 250 mg, for the treatment of patients with coronavirus infection (light and medium-heavy form), the appointment in the "off-label" in comparison with the drug Hydroxychloroquine tablets 200 mg, when administered in the mode "off label".
2. To study the effectiveness of the drug Mefloquine, tablet 250 mg, when administered in the mode "off label", in comparison with the drug Hydroxychloroquine tablets 200 mg, when administered in the mode "off label" when applied to a schema for the treatment of patients with severe coronavirus infection.
3. Evaluate the safety and tolerability of Mefloquine, 250 mg tablets, and Hydroxychloroquine, 200 mg tablets, for the treatment of patients with coronavirus infection (mild and moderate-severe forms).
4. Evaluate the safety and tolerability of Mefloquine, 250 mg tablets, and Hydroxychloroquine, 200 mg tablets, for the treatment of patients with coronavirus infection (severe forms), when used as part of a regimen for the treatment of patients with severe coronavirus infection.

Study design:

An open, randomized, multicenter comparative study of the efficacy and safety of Mefloquine and Hydroxychloroquine in "off-label" mode for the treatment of patients with COVID-19 coronavirus infection

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 123098
    • Burnasyan Federal Medical Biophysical Center FMBA of Russia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients aged 18 years and older COVID19 positive confirmed by PCR, without ARDS and sepsis.
• Hospitalization of the patient.
• Signed informed consent for participation in the study.

Exclusion Criteria:

• The criteria for retiring a volunteer during the screening period are:

  1. Revoking informed consent of patients.
  2. Non-compliance of the volunteer with the inclusion criteria.
  3. First identified the condition and/or disease described in the criteria for inclusion.
  4. Positive test for HIV infection, Hepatitis B, C, syphilis.

The criteria for early termination of participation of volunteers in the study during the period of use of the study drug are:

1. Withdrawal of informed consent by a volunteer.
2. First identified the condition and/or disease described in the criteria for inclusion.
3. Occurrence of serious adverse events.
4. Adverse events that do not meet the criteria of severity, in the development of which, in the opinion of the researcher, further participation in the study may be harmful to the health or well-being of the volunteer.
5. The need for patients included in the study, antibiotics of the fluoroquinolone group.
6. Administrative reasons (termination of the study by the Sponsor or regulatory authorities), as well as gross violations of the Protocol that may affect the results of the study.
7. the Patient receives / needs additional treatment that may affect the outcome of the study or the patient's safety
8. Individual intolerance to research drugs
9. Erroneous inclusion (for example, the patient was included in violation of the criteria for inclusion/non-inclusion of the Protocol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: group 1 cohort 1; 80 patients who receive Mefloquine prescribed according to the following scheme: 1st day: 750 mg of mefloquine per day, inside, in tablets of 250 mg 3 times a day - 1 tablet every 8 hours.; Day 2: 500 mg of mefloquine, inside, in tablets of 250 mg 2 times a day - 1 tablet every 12 hours.; 3rd - 7th day: 250 mg of mefloquine, inside, in tablets of 250 mg 1 time a day at the same time.	Drug: Mefloquine; 1st day: 750 mg of mefloquine per day, inside, in tablets of 250 mg 3 times a day - 1 tablet every 8 hours.; Day 2: 500 mg of mefloquine, inside, in tablets of 250 mg 2 times a day - 1 tablet every 12 hours.; 3rd - 7th day: 250 mg of mefloquine, inside, in tablets of 250 mg 1 time a day at the same time.
EXPERIMENTAL: group 1 cohort 2; 80 patients who receive Hydroxychloroquine prescribed according to the following scheme: • 1st day: 800 mg of hydroxychloroquine per day, inside, in 200 mg tablets, 2 tablets 2 times a day; 2nd - 7th day: 400 mg of hydroxychloroquine per day, inside, in tablets of 200 mg, 1 tablet 2 times a day.	Drug: Hydroxychloroquine; st day: 800 mg of hydroxychloroquine per day, inside, in 200 mg tablets, 2 tablets 2 times a day;; nd - 7th day: 400 mg of hydroxychloroquine per day, inside, in tablets of 200 mg, 1 tablet 2 times a day.
EXPERIMENTAL: group 2 cohort 1; A concomitant therapy consisting of Mefloquine in conjunction with azithromycin and tocilizumab will be given for 80 patients. Dosage of Mefloquine is same as for group 1 cohort 1.	Combination product: Mefloquine + azithromycin + / - tocilizumab; 1st day: 750 mg of mefloquine per day, inside, in tablets of 250 mg 3 times a day - 1 tablet every 8 hours.; Day 2: 500 mg of mefloquine, inside, in tablets of 250 mg 2 times a day - 1 tablet every 12 hours.; 3rd - 7th day: 250 mg of mefloquine, inside, in tablets of 250 mg 1 time a day at the same time.
EXPERIMENTAL: group 2 cohort 2; A concomitant therapy consisting of Hydroxychloroquine in conjunction with azithromycin and tocilizumab will be given for 80 patients. Dosage of Hydroxychloroquine is same as for group 1 cohort 2.	Combination product: Hydroxychloroquine + azithromycin + / - tocilizumab; st day: 800 mg of hydroxychloroquine per day, inside, in 200 mg tablets, 2 tablets 2 times a day;; nd - 7th day: 400 mg of hydroxychloroquine per day, inside, in tablets of 200 mg, 1 tablet 2 times a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1st primary endpoint for group 1	The number of patients with development of respiratory failure requiring transfer to the ICU.	up to 10 days
2nd primary endpoint for group 1	The period of clinical recovery.	up to 10 days
1st primary endpoint for group 2	The period of clinical recovery.	up to 10 days
2nd primary endpoint for group 2	Frequency of fatal outcomes associated with coronavirus infection disease (COVID19)	through study completion, an average of 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1st secondary endpoint for group 1	A change in viral load by conducting PCR assay through different timeframes	on days 5 and 10
2nd secondary endpoint for group 1	Frequency of clinical cure on day 10 from the start of therapy	on day 10
3d secondary endpoint for group 1	The retention time of the reaction temperature from the start of the treatment.	up to 10 days
4th secondary endpoint for group 1	Concentration of C-reactive protein in blood plasma.	up to 10 days
5th secondary endpoint for group 1	Respiratory index.	up to 10 days
6th secondary endpoint for group 1	Frequency appearance unwanted phenomena and serious unwanted phenomena	up to 10 days
1st secondary endpoint for group 2	A change in viral load by conducting PCR assay through different timeframes	on days 5 and 10
2nd secondary endpoint for group 2	Respiratory index.	up to 10 days
3d secondary endpoint for group 2	The retention time of the reaction temperature from the start of treatment.	up to 10 days
4th secondary endpoint for group 2	Concentration of C-reactive protein in blood plasma.	up to 10 days
5th secondary endpoint for group 2	Number of patients required transition to alternative therapy schedule	up to 10 days
6th secondary endpoint for group 2	Frequency of adverse events and serious adverse events	up to 10 days

Collaborators and Investigators

• Sponsor: Burnasyan Federal Medical Biophysical Center
• Investigators: Principal Investigator: Tatiana Astrelina, MD PhD,DSc., Burnasyan FMBC SRC FMBA of Russia

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 8, 2020
• Primary Completion (ACTUAL): November 1, 2020
• Study Completion (ACTUAL): November 20, 2020

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (ACTUAL): April 15, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia; Lung Diseases; Respiratory Insufficiency; Pneumonia, Viral; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine; Mefloquine
• Other Study ID Numbers: FL-01/20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No