Clinical trial NCT05689827: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthenia
COVID-19
Lead sponsor: Promomed, LLC
Sponsor class: OTHER
First posted: 2023-01-19
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Patients able to sign the patient informed consent form for the participation in the clinical study
2. Patients of both sexes of 18-65 years of age
3. Patient's negative test result for severe acute respiratory syndrome (SARS) -CoV-2 RNA obtained by polymerase chain reaction (PCR) method within 72 hours
4. COVID-19 diagnosis documented in the history more than 12 weeks ago\*
5. 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
6. Patients capable of following the requirements of the Clinical Study Protocol
7. Negative pregnancy test result (for women with the active childbearing potential)
8. MFI-20 scale score is more than 30 at the moment of screening.

Exclusion Criteria:

1. Allergic reactions to the components of the study product
2. Oxygen saturation by pulse oximetry (SpO2) oxygen saturation ≤ 95%
3. Depression level score by Hamilton Depression Rating Scale (HDRS) at the screening ≥ 8
4. Intracranial pressure rise (for the reason of venous outflow disorder and intracranial tumours)
5. Severe hepatic failure
6. Severe renal failure
7. Chronic liver and hepatic diseases
8. Thyroid diseases
9. Anaemia
10. Malignant tumour of any localization currently or during 5 years before the inclusion into the study except for completely treated carcinoma in situ
11. Autoimmune diseases
12. Other chronical diseases which, according to the investigator, can cause asthenia
13. G lomerular filtration rate (GFR) parameter at screening \< 30 mL/min
14. Pregnancy or lactation period
15. Participation in any other clinical study during the last 3 months
16. Tuberculosis, cancers or positive reaction to the HIV infection, hepatitis B \& C, syphilis according to the history data
17. Severe eyesight and/or hearing disorders, serious articulation disorders and/or other deviations able to prevent the patient from adequate cooperation during the study)
18. Mental disorders in the history
19. Alcohol, drug abuse or drug dependence in the history
20. 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
21. 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

1. Erroneous inclusion (inclusion and exclusion criteria violation).
2. Investigator or Sponsor's decision to exclude the patient from the study because of clinically significant deviation from protocol/protocol violation.
3. 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.
4. 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.
5. Patient's refusal to continue the participation in the study or his/her lack of discipline.
6. Allergic reaction to the study drug intake, which require its discontinuation.
7. Patient's wish to prematurely terminate the study for any reason.
8. Loss of contact with the patient and his/her absence for the visit.
9. Necessity to use a therapy prohibited by this protocol.
10. Occurrence of pregnancy.

Primary outcomes:
measure: Asthenia on a scale Multidimensional Fatigue Inventory (MFI-20) after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
Secondary outcomes:
measure: Asthenia on a scale MFI-20 after the completion of the parenteral therapy
timeFrame: From baseline to Visit 3 (day 11)
measure: Asthenia on a scale MFI-20 after the completion of the oral therapy
timeFrame: From Visit 3 (day 11) to Visit 5 (day 41)
measure: Headache on a visual analogue scale (VAS) after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
measure: Headache on a VAS after the completion of the parenteral therapy
timeFrame: From baseline to Visit 3 (day 11)
measure: Headache on a VAS after the completion of the oral therapy
timeFrame: From Visit 3 (day 11) to Visit 5 (day 41)
measure: Sleep Quality on a Pittsburgh sleep quality index (PSQI) after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
measure: Fatigue on a Fatigue Assessment Scale (FAS-10) scale after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
measure: Fatigue on a FAS-10 scale after the completion of the parenteral therapy
timeFrame: From baseline to Visit 3 (day 11)
measure: Fatigue on a FAS-10 scale after the completion of the oral therapy
timeFrame: From Visit 3 (day 11) to Visit 5 (day 41)
measure: Dizziness on a Dizziness Handicap Inventory (DHI) questionnaire after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
measure: Dizziness on a DHI questionnaire after the completion of the parenteral therapy
timeFrame: From baseline to Visit 3 (day 11)
measure: Dizziness on a DHI questionnaire after the completion of the oral therapy
timeFrame: From Visit 3 (day 11) to Visit 5 (day 41)
measure: Cognitive function on a Monreal Gognitive Assessment (MoCA) scale after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
measure: Anxiety on a Beck scale after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
measure: Anxiety on a Beck scale after the completion of the parenteral therapy
timeFrame: From baseline to Visit 3 (day 11)
measure: Anxiety on a Beck scale after the completion of the oral therapy
timeFrame: From Visit 3 (day 11) to Visit 5 (day 41)
measure: Regulatory function on a Kerdo vegetation index after the completion of the sequential therapy
timeFrame: From baseline to Visit 5 (day 41)
measure: Regulatory function on a Kerdo vegetation index after the completion of the parenteral therapy
timeFrame: From baseline to Visit 3 (day 11)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Research Institution "Research Centre of Neurology"
city: Saint Petersburg
country: Russian Federation
facility: OsteoVita LLC
city: Sestroretsk
country: Russian Federation
facility: Saint Petersburg State Budgetary Healthcare Institution "Municipal Hospital No. 40 of Kurortny District"
city: Yaroslavl
country: Russian Federation
facility: Centre For Evidence-Based Medicine Llc
city: Yaroslavl
country: Russian Federation
facility: Medical Centre of Diagnostics and Prevention Plus LLC
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Healthcare Institution of Yaroslavl Region "Yaroslavl Region Clinical Hospital for War Veterans - International Elderly People Centre 'Zdorovoe Dolgoletie'
Study officials:
References:
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.