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Safety and Efficacy of the Therapy With BRAINMAX® for the Treatment of Patients With Asthenia After COVID-19

Primary Purpose

Asthenia, COVID-19

Status
Completed
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
Ethyl methyl hydroxypyridine succinate + Meldonium
Placebo
Sponsored by
Promomed, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients able to sign the patient informed consent form for the participation in the clinical study Patients of both sexes of 18-65 years of age Patient's negative test result for severe acute respiratory syndrome (SARS) -CoV-2 RNA obtained by polymerase chain reaction (PCR) method within 72 hours COVID-19 diagnosis documented in the history more than 12 weeks ago* Minimum two symptoms of asthenic state: fatigue, atony, dizziness, sleeping disorder, feeling of energy loss and decreased functioning, intellectual function disorder, attention and memory disorder, which appeared during or after COVID-19, retain for more than 12 weeks and cannot be explained by an alternative diagnosis Patients capable of following the requirements of the Clinical Study Protocol Negative pregnancy test result (for women with the active childbearing potential) MFI-20 scale score is more than 30 at the moment of screening. Exclusion Criteria: Allergic reactions to the components of the study product Oxygen saturation by pulse oximetry (SpO2) oxygen saturation ≤ 95% Depression level score by Hamilton Depression Rating Scale (HDRS) at the screening ≥ 8 Intracranial pressure rise (for the reason of venous outflow disorder and intracranial tumours) Severe hepatic failure Severe renal failure Chronic liver and hepatic diseases Thyroid diseases Anaemia Malignant tumour of any localization currently or during 5 years before the inclusion into the study except for completely treated carcinoma in situ Autoimmune diseases Other chronical diseases which, according to the investigator, can cause asthenia G lomerular filtration rate (GFR) parameter at screening < 30 mL/min Pregnancy or lactation period Participation in any other clinical study during the last 3 months Tuberculosis, cancers or positive reaction to the HIV infection, hepatitis B & C, syphilis according to the history data Severe eyesight and/or hearing disorders, serious articulation disorders and/or other deviations able to prevent the patient from adequate cooperation during the study) Mental disorders in the history Alcohol, drug abuse or drug dependence in the history Patients which, according to the investigator, are obviously or probably incapable of understanding and evaluating this study information within the process of the informed consent form signing, including but not limited to with regard to expected risks and possible discomfort Other diseases, symptoms or conditions not listed above, which, according to the investigator, are predicaments for the participation in the clinical study Exclusion of patients from the study Erroneous inclusion (inclusion and exclusion criteria violation). Investigator or Sponsor's decision to exclude the patient from the study because of clinically significant deviation from protocol/protocol violation. Serious adverse events or adverse events which do not meet the seriousness criteria and which if developed, according to the investigator, can make the patient's further participation in the study harmful for the patient's health or wellbeing. Any adverse event (there might be no connection with the study drug intake) requiring the observation, procedures and/or drug treatment not allowed by this study protocol. Patient's refusal to continue the participation in the study or his/her lack of discipline. Allergic reaction to the study drug intake, which require its discontinuation. Patient's wish to prematurely terminate the study for any reason. Loss of contact with the patient and his/her absence for the visit. Necessity to use a therapy prohibited by this protocol. Occurrence of pregnancy.

Sites / Locations

  • Federal State Budgetary Research Institution "Research Centre of Neurology"
  • OsteoVita LLC
  • Saint Petersburg State Budgetary Healthcare Institution "Municipal Hospital No. 40 of Kurortny District"
  • Centre For Evidence-Based Medicine Llc
  • Medical Centre of Diagnostics and Prevention Plus LLC
  • State Budgetary Healthcare Institution of Yaroslavl Region "Yaroslavl Region Clinical Hospital for War Veterans - International Elderly People Centre 'Zdorovoe Dolgoletie'

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ethyl methyl hydroxypyridine succinate + Meldonium

Placebo

Arm Description

Arm 1 (n=80) received intramuscularly with the dosage regimen of 5 mL of solution (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) once per day for 10 days; total number of injections for the treatment course is 10 and then orally with the dosage regimen of 2 capsules (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) twice per day for 30 days; total number of capsules for the treatment course is 120. Second group received Placebo in the same way.

Arm 2 (n=80) received Placebo in the same way.

Outcomes

Primary Outcome Measures

Asthenia on a scale Multidimensional Fatigue Inventory (MFI-20) after the completion of the sequential therapy
Mean decrease of MFI-20 asthenia scale score after the completion of the sequential therapy

Secondary Outcome Measures

Asthenia on a scale MFI-20 after the completion of the parenteral therapy
Mean decrease of MFI-20 asthenia scale score after the completion of the parenteral therapy
Asthenia on a scale MFI-20 after the completion of the oral therapy
Mean decrease of MFI-20 asthenia scale score after the completion of the oral therapy
Headache on a visual analogue scale (VAS) after the completion of the sequential therapy
Score dynamics by VAS for the headache evaluation after the completion of the sequential therapy
Headache on a VAS after the completion of the parenteral therapy
Score dynamics by VAS for the headache evaluation after the completion of the parenteral therapy
Headache on a VAS after the completion of the oral therapy
Score dynamics by VAS for the headache evaluation after the completion of the oral therapy
Sleep Quality on a Pittsburgh sleep quality index (PSQI) after the completion of the sequential therapy
Score dynamics by PSQI questionnaire after the completion of the sequential therapy
Fatigue on a Fatigue Assessment Scale (FAS-10) scale after the completion of the sequential therapy
Score dynamics by FAS-10 scale after the completion of the sequential therapy
Fatigue on a FAS-10 scale after the completion of the parenteral therapy
Score dynamics by FAS-10 scale after the completion of the parenteral therapy
Fatigue on a FAS-10 scale after the completion of the oral therapy
Score dynamics by FAS-10 scale after the completion of the oral therapy
Dizziness on a Dizziness Handicap Inventory (DHI) questionnaire after the completion of the sequential therapy
Score dynamics by DHI questionnaire after the completion of the sequential therapy
Dizziness on a DHI questionnaire after the completion of the parenteral therapy
Score dynamics by DHI questionnaire after the completion of the parenteral therapy
Dizziness on a DHI questionnaire after the completion of the oral therapy
Score dynamics by DHI questionnaire after the completion of the oral therapy
Cognitive function on a Monreal Gognitive Assessment (MoCA) scale after the completion of the sequential therapy
Score dynamics by MoCA scale after the completion of the sequential therapy
Anxiety on a Beck scale after the completion of the sequential therapy
Score dynamics by Beck scale after the completion of the sequential therapy
Anxiety on a Beck scale after the completion of the parenteral therapy
Score dynamics by Beck scale after the completion of the parenteral therapy
Anxiety on a Beck scale after the completion of the oral therapy
Score dynamics by Beck scale after the completion of the oral therapy
Regulatory function on a Kerdo vegetation index after the completion of the sequential therapy
Changes in values of Kerdo vegetation index after the completion of the sequential therapy
Regulatory function on a Kerdo vegetation index after the completion of the parenteral therapy
Changes in values of Kerdo vegetation index after the completion of the parenteral therapy

Full Information

First Posted
January 18, 2023
Last Updated
July 11, 2023
Sponsor
Promomed, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05689827
Brief Title
Safety and Efficacy of the Therapy With BRAINMAX® for the Treatment of Patients With Asthenia After COVID-19
Official Title
Prospective Multicentre Comparative Randomized Double Blind Placebo Controlled Study of Safety and Efficacy of the Therapy With BRAINMAX® for the Treatment of Patients With Asthenia After Having the Novel Coronavirus Infection (COVID-19)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 5, 2022 (Actual)
Primary Completion Date
November 10, 2022 (Actual)
Study Completion Date
November 10, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Promomed, LLC

4. Oversight

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

5. Study Description

Brief Summary
This is prospective multicentre comparative randomized double blind placebo controlled study conducted in 6 medical facilities.The objective of the study is to assess the safety and efficacy of the sequential therapy with BRAINMAX®, solution for intravenous infusion and intramuscular injection, and BRAINMAX®, capsules for the treatment of patients with asthenia after having the novel coronavirus infection (COVID-19)
Detailed Description
Upon signing the informed consent form and screening, 160 eligible patients from 18 to 65 years of age with asthenia after having the novel coronavirus infection (COVID-19) were randomized at a 1:1 ratio. First group received intramuscularly with the dosage regimen of 5 mL of solution (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) once per day for 10 days; total number of injections for the treatment course is 10 and then orally with the dosage regimen of 2 capsules (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) twice per day for 30 days; total number of capsules for the treatment course is 120. Second group received Placebo in the same way.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthenia, COVID-19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ethyl methyl hydroxypyridine succinate + Meldonium
Arm Type
Experimental
Arm Description
Arm 1 (n=80) received intramuscularly with the dosage regimen of 5 mL of solution (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) once per day for 10 days; total number of injections for the treatment course is 10 and then orally with the dosage regimen of 2 capsules (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) twice per day for 30 days; total number of capsules for the treatment course is 120. Second group received Placebo in the same way.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Arm 2 (n=80) received Placebo in the same way.
Intervention Type
Drug
Intervention Name(s)
Ethyl methyl hydroxypyridine succinate + Meldonium
Other Intervention Name(s)
BRAINMAX®
Intervention Description
Ethyl methyl hydroxypyridine succinate 100.0 mg/mL, meldonium dihydrate - 100.0 mg/mL (Solution for intravenous and intramuscular administration), then Ethyl methyl hydroxypyridine succinate - 250.0 mg, meldonium dihydrate based on dihydrate without adsorption moisture - 250.0 mg (oral capsules)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo was used in the same way
Primary Outcome Measure Information:
Title
Asthenia on a scale Multidimensional Fatigue Inventory (MFI-20) after the completion of the sequential therapy
Description
Mean decrease of MFI-20 asthenia scale score after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Secondary Outcome Measure Information:
Title
Asthenia on a scale MFI-20 after the completion of the parenteral therapy
Description
Mean decrease of MFI-20 asthenia scale score after the completion of the parenteral therapy
Time Frame
From baseline to Visit 3 (day 11)
Title
Asthenia on a scale MFI-20 after the completion of the oral therapy
Description
Mean decrease of MFI-20 asthenia scale score after the completion of the oral therapy
Time Frame
From Visit 3 (day 11) to Visit 5 (day 41)
Title
Headache on a visual analogue scale (VAS) after the completion of the sequential therapy
Description
Score dynamics by VAS for the headache evaluation after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Title
Headache on a VAS after the completion of the parenteral therapy
Description
Score dynamics by VAS for the headache evaluation after the completion of the parenteral therapy
Time Frame
From baseline to Visit 3 (day 11)
Title
Headache on a VAS after the completion of the oral therapy
Description
Score dynamics by VAS for the headache evaluation after the completion of the oral therapy
Time Frame
From Visit 3 (day 11) to Visit 5 (day 41)
Title
Sleep Quality on a Pittsburgh sleep quality index (PSQI) after the completion of the sequential therapy
Description
Score dynamics by PSQI questionnaire after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Title
Fatigue on a Fatigue Assessment Scale (FAS-10) scale after the completion of the sequential therapy
Description
Score dynamics by FAS-10 scale after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Title
Fatigue on a FAS-10 scale after the completion of the parenteral therapy
Description
Score dynamics by FAS-10 scale after the completion of the parenteral therapy
Time Frame
From baseline to Visit 3 (day 11)
Title
Fatigue on a FAS-10 scale after the completion of the oral therapy
Description
Score dynamics by FAS-10 scale after the completion of the oral therapy
Time Frame
From Visit 3 (day 11) to Visit 5 (day 41)
Title
Dizziness on a Dizziness Handicap Inventory (DHI) questionnaire after the completion of the sequential therapy
Description
Score dynamics by DHI questionnaire after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Title
Dizziness on a DHI questionnaire after the completion of the parenteral therapy
Description
Score dynamics by DHI questionnaire after the completion of the parenteral therapy
Time Frame
From baseline to Visit 3 (day 11)
Title
Dizziness on a DHI questionnaire after the completion of the oral therapy
Description
Score dynamics by DHI questionnaire after the completion of the oral therapy
Time Frame
From Visit 3 (day 11) to Visit 5 (day 41)
Title
Cognitive function on a Monreal Gognitive Assessment (MoCA) scale after the completion of the sequential therapy
Description
Score dynamics by MoCA scale after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Title
Anxiety on a Beck scale after the completion of the sequential therapy
Description
Score dynamics by Beck scale after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Title
Anxiety on a Beck scale after the completion of the parenteral therapy
Description
Score dynamics by Beck scale after the completion of the parenteral therapy
Time Frame
From baseline to Visit 3 (day 11)
Title
Anxiety on a Beck scale after the completion of the oral therapy
Description
Score dynamics by Beck scale after the completion of the oral therapy
Time Frame
From Visit 3 (day 11) to Visit 5 (day 41)
Title
Regulatory function on a Kerdo vegetation index after the completion of the sequential therapy
Description
Changes in values of Kerdo vegetation index after the completion of the sequential therapy
Time Frame
From baseline to Visit 5 (day 41)
Title
Regulatory function on a Kerdo vegetation index after the completion of the parenteral therapy
Description
Changes in values of Kerdo vegetation index after the completion of the parenteral therapy
Time Frame
From baseline to Visit 3 (day 11)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients able to sign the patient informed consent form for the participation in the clinical study Patients of both sexes of 18-65 years of age Patient's negative test result for severe acute respiratory syndrome (SARS) -CoV-2 RNA obtained by polymerase chain reaction (PCR) method within 72 hours COVID-19 diagnosis documented in the history more than 12 weeks ago* Minimum two symptoms of asthenic state: fatigue, atony, dizziness, sleeping disorder, feeling of energy loss and decreased functioning, intellectual function disorder, attention and memory disorder, which appeared during or after COVID-19, retain for more than 12 weeks and cannot be explained by an alternative diagnosis Patients capable of following the requirements of the Clinical Study Protocol Negative pregnancy test result (for women with the active childbearing potential) MFI-20 scale score is more than 30 at the moment of screening. Exclusion Criteria: Allergic reactions to the components of the study product Oxygen saturation by pulse oximetry (SpO2) oxygen saturation ≤ 95% Depression level score by Hamilton Depression Rating Scale (HDRS) at the screening ≥ 8 Intracranial pressure rise (for the reason of venous outflow disorder and intracranial tumours) Severe hepatic failure Severe renal failure Chronic liver and hepatic diseases Thyroid diseases Anaemia Malignant tumour of any localization currently or during 5 years before the inclusion into the study except for completely treated carcinoma in situ Autoimmune diseases Other chronical diseases which, according to the investigator, can cause asthenia G lomerular filtration rate (GFR) parameter at screening < 30 mL/min Pregnancy or lactation period Participation in any other clinical study during the last 3 months Tuberculosis, cancers or positive reaction to the HIV infection, hepatitis B & C, syphilis according to the history data Severe eyesight and/or hearing disorders, serious articulation disorders and/or other deviations able to prevent the patient from adequate cooperation during the study) Mental disorders in the history Alcohol, drug abuse or drug dependence in the history Patients which, according to the investigator, are obviously or probably incapable of understanding and evaluating this study information within the process of the informed consent form signing, including but not limited to with regard to expected risks and possible discomfort Other diseases, symptoms or conditions not listed above, which, according to the investigator, are predicaments for the participation in the clinical study Exclusion of patients from the study Erroneous inclusion (inclusion and exclusion criteria violation). Investigator or Sponsor's decision to exclude the patient from the study because of clinically significant deviation from protocol/protocol violation. Serious adverse events or adverse events which do not meet the seriousness criteria and which if developed, according to the investigator, can make the patient's further participation in the study harmful for the patient's health or wellbeing. Any adverse event (there might be no connection with the study drug intake) requiring the observation, procedures and/or drug treatment not allowed by this study protocol. Patient's refusal to continue the participation in the study or his/her lack of discipline. Allergic reaction to the study drug intake, which require its discontinuation. Patient's wish to prematurely terminate the study for any reason. Loss of contact with the patient and his/her absence for the visit. Necessity to use a therapy prohibited by this protocol. Occurrence of pregnancy.
Facility Information:
Facility Name
Federal State Budgetary Research Institution "Research Centre of Neurology"
City
Moscow
Country
Russian Federation
Facility Name
OsteoVita LLC
City
Saint Petersburg
Country
Russian Federation
Facility Name
Saint Petersburg State Budgetary Healthcare Institution "Municipal Hospital No. 40 of Kurortny District"
City
Sestroretsk
Country
Russian Federation
Facility Name
Centre For Evidence-Based Medicine Llc
City
Yaroslavl
Country
Russian Federation
Facility Name
Medical Centre of Diagnostics and Prevention Plus LLC
City
Yaroslavl
Country
Russian Federation
Facility Name
State Budgetary Healthcare Institution of Yaroslavl Region "Yaroslavl Region Clinical Hospital for War Veterans - International Elderly People Centre 'Zdorovoe Dolgoletie'
City
Yaroslavl
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
37167167
Citation
Tanashyan MM, Raskurazhev AA, Kuznetsova PI, Bely PA, Zaslavskaya KI. [Prospects and possibilities for the treatment of patients with long COVID-19 syndrome]. Ter Arkh. 2022 Dec 26;94(11):1285-1293. doi: 10.26442/00403660.2022.11.201981. Russian.
Results Reference
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Links:
URL
https://cyberleninka.ru/article/n/perspektivy-i-vozmozhnosti-terapii-patsientov-s-astenicheskim-sindromom-posle-perenesennoy-novoy-koronavirusnoy-infektsii-covid-19
Description
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Safety and Efficacy of the Therapy With BRAINMAX® for the Treatment of Patients With Asthenia After COVID-19

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