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

• ClinicalTrials.gov Identifier: NCT04347031
• Recruitment Status: Completed
• First Posted: April 15, 2020
• Last Update Posted: January 27, 2021
• Sponsor: Burnasyan Federal Medical Biophysical Center
• Information provided by (Responsible Party): Tatyana Astrelina, Burnasyan Federal Medical Biophysical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pneumonia, Viral; Respiratory Failure	Drug: Mefloquine; Drug: Hydroxychloroquine; Combination Product: Mefloquine + azithromycin + / - tocilizumab; Combination Product: Hydroxychloroquine + azithromycin + / - tocilizumab	Phase 2; Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 320 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 8, 2020
• Actual Primary Completion Date: November 1, 2020
• Actual Study Completion Date: November 20, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 1st primary endpoint for group 1 [ Time Frame: up to 10 days ]
   The number of patients with development of respiratory failure requiring transfer to the ICU.
2. 2nd primary endpoint for group 1 [ Time Frame: up to 10 days ]
   The period of clinical recovery.
3. 1st primary endpoint for group 2 [ Time Frame: up to 10 days ]
   The period of clinical recovery.
4. 2nd primary endpoint for group 2 [ Time Frame: through study completion, an average of 3 months ]
   Frequency of fatal outcomes associated with coronavirus infection disease (COVID19)

Secondary Outcome Measures :

1. 1st secondary endpoint for group 1 [ Time Frame: on days 5 and 10 ]
   A change in viral load by conducting PCR assay through different timeframes
2. 2nd secondary endpoint for group 1 [ Time Frame: on day 10 ]
   Frequency of clinical cure on day 10 from the start of therapy
3. 3d secondary endpoint for group 1 [ Time Frame: up to 10 days ]
   The retention time of the reaction temperature from the start of the treatment.
4. 4th secondary endpoint for group 1 [ Time Frame: up to 10 days ]
   Concentration of C-reactive protein in blood plasma.
5. 5th secondary endpoint for group 1 [ Time Frame: up to 10 days ]
   Respiratory index.
6. 6th secondary endpoint for group 1 [ Time Frame: up to 10 days ]
   Frequency appearance unwanted phenomena and serious unwanted phenomena
7. 1st secondary endpoint for group 2 [ Time Frame: on days 5 and 10 ]
   A change in viral load by conducting PCR assay through different timeframes
8. 2nd secondary endpoint for group 2 [ Time Frame: up to 10 days ]
   Respiratory index.
9. 3d secondary endpoint for group 2 [ Time Frame: up to 10 days ]
   The retention time of the reaction temperature from the start of treatment.
10. 4th secondary endpoint for group 2 [ Time Frame: up to 10 days ]
    Concentration of C-reactive protein in blood plasma.
11. 5th secondary endpoint for group 2 [ Time Frame: up to 10 days ]
    Number of patients required transition to alternative therapy schedule
12. 6th secondary endpoint for group 2 [ Time Frame: up to 10 days ]
    Frequency of adverse events and serious adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

Russian Federation

Burnasyan Federal Medical Biophysical Center FMBA of Russia

Moscow, Russian Federation, 123098

Sponsors and Collaborators

Burnasyan Federal Medical Biophysical Center

Investigators

• Principal Investigator: Tatiana Astrelina, MD PhD,DSc.; Burnasyan FMBC SRC FMBA of Russia

More Information

• Responsible Party: Tatyana Astrelina, MD PhD, DSc (medicine), Head of Center for Biomedical Technologies State Research Center Burnasyan Federal Medical Biophysical Center FMBA of Russia, Burnasyan Federal Medical Biophysical Center
• ClinicalTrials.gov Identifier: NCT04347031
• Other Study ID Numbers: FL-01/20
• First Posted: April 15, 2020
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pneumonia, Viral; Pneumonia; Respiratory Insufficiency; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Respiration Disorders; Virus Diseases; Azithromycin; Hydroxychloroquine; Mefloquine; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents