Results of clinical studies of the efficacy and safety of the use of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia
Author:
M.V. ZHURAVLEVA1,2, P.R. KAMCHATNOV3, N.S. VASYUKOVA4, V.V. ARKHIPOV1, E.V. KUZNETSOVA5, T.R. KAMENEVA6, S.YU. SEREBROVA1,2
1Research Center for Examination of Medical Devices, Moscow, Russia;
2Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
3Pirogov Russian National Research Medical University, Moscow, Russia;
4Skriabin and Kovalenko Institute of Experimental Veterinary Medicine, Moscow, Russia;
5Research Institute for Healthcare and Medical Management, Moscow, Russia;
6Konchalovsky City Clinical Hospital, Moscow, Russia
Summary:
Chronic cerebral ischemia (CCI) is a common syndrome that, in the absence of adequate therapy, is characterized by a progressive course, an increase in cognitive, emotional, motor and other disorders, eventually leading to persistent disability of the patient. In the treatment of patients with CCI, the use of drugs with a multimodal neuroprotective effect is indicated. The results of the analysis of a series of clinical trials of the drugs Mexidol and Mexidol FORTE in patients with CCI are presented. The effects in relation to cognitive, emotional, asthenic, vegetative and other manifestations of CCI are considered. It is concluded that it is advisable to consistently use the drugs Mexidol and Mexidol FORTE in such patients. Keywords: chronic cerebral ischemia, cognitive impairment, Mexidol, emotional disorders, treatment.
Efficacy of Mexidol in patients with chronic brain ischemia and cognitive impairment of different age groups (results of sub-analysis of the international multicenter, randomized, double-blind, placebo-controlled study of sequential therapy in patients with chronic brain ischemia MEMO)
Author:
V.V. ZAKHAROV1, O.N. TKACHEVA2,3, E.A. MKHITARYAN2,3, A.I. FEDIN2
1Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2Pirogov Russian National Research Medical University , Moscow, Russia;
3Russian Clinical and Research Center of Gerontology, Pirogov Russian National Research Medical University , Moscow, Russia
Summary:
Objective. To assess the efficacy of sequential therapy with Mexidol and Mexidol FORTE 250 in comparison with placebo in patients of different age groups with chronic brain ischemia. Material and methods. The study is sub-analysis of data of the international multicenter, randomized, double-blind, placebo-controlled study of sequential therapy in patients with chronic brain ischemia (MEMO), which included 318 patients (25% men) in the age of 40—90 (median 60) years. All subjects were subdivided into 3 age subgroups: 40—60 years (n=163), 61—75 years (n=141) and 76—90 years (n=13). The primary efficacy endpoint was the dynamic of increase of total score by MoCA scale, i.e. the absolute value of difference by MoCA scale at the point of day 75 comparing to values before treatment. As secondary efficacy endpoints results of dynamic by following questionnaires and scales were used: digit symbol substitution test, the Health Survey SF-36, asthenia subjective assessment scale (MFI-20), Vane questionnaire, Beck anxiety scale, Tinetti scale. Results. After 75 days of treatment positive dynamic was revealed in cognitive, emotional and motor impairment in patients of 40—60 and 61—75 age subgroups both in groups of Mexidol and placebo, but in group of Mexidol the changes were more prominent which is proved by significantly higher values of median of absolute difference of total score of studied parameters. Conclusion. The results of trial showed that in patients of different age-subgroups with chronic brain ischemia the improvement in cognitive, motor impairment and quality of life, as well as decrease in vegetative impairment, asthenia and anxiety are observed after 75 days of treatment both in Mexidol and placebo group, but in Mexidol group these changes are more prominent. The data obtained confirm the expediency of the use of sequential therapy with Mexidol and Mexidol FORTE 250 in patients of different age subgroups with chronic brain ischemia. Keywords: cognitive impairment, chronic brain ischemia, Mexidol , Mexidol FORTE 250, ethylmethylhydroxypyridine succinate, MEMO trial.
Safety of Mexidol® (ethylmethylhydroxypyridine succinate) in adult patients of different age groups
Author:
E.A. USHKALOVA1, S.K. ZYRYANOV1,2, O.I. BUTRANOVA1
1RUDN University, Moscow; 2City Clinical Hospital No. 24, Department of Healthcare of Moscow, Moscow
Summary:
To reduce the risk of developing adverse events (AEs) and increase the adherence of elderly patients to treatment, it is recommended to limit maximally the total number of prescribed drugs (DR), using one drug for the treatment of two or more pathologies if possible. The drugs that meet the criteria for use in elderly patients and / or patients with comorbidity include the original Russian drug Mexidol® (ethylmethylhydroxypyridine succinate), which has a multimodal mechanism of action and has multiple pharmacological effects. In order to study the safety of Mexidol in comparison with placebo in different age groups of patients with chronic cerebral ischemia, a post hoc analysis of the international multicenter, randomized, double-blind, placebo-controlled MEMO study with an adaptive design was carried out, which assessed the efficacy and safety of sequential therapy with Mexidol®, a solution for intravenous and intramuscular injection, 50 mg/ml (NPK PHARMASOFT, Russia) and Mexidol® FORTE 250 film-coated tablets, 250 mg (NPK PHARMASOFT, Russia) in patients with chronic cerebral ischemia. The study involved 318 patients aged from 40 to 90 years. Comparable safety and tolerability of Mexidol was demonstrated in middle-aged and elderly people with chronic cerebral ischemia, including patients over 75 years of age. Keywords: adult patients of different age groups; elderly; MEMO research; Mexidol®; Mexidol® FORTE 250; ethylmethylhydroxypyridine succinate; safety.
Hypoxia and oxidative stress in cerebral circulation insufficiency — effective ways of correction
Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, D.M. RODIONOVA
Pirogov Russian National Research Medical University, Moscow, Russia
Summary:
Cerebrovascular diseases (CVDs) are one of the urgent problems of clinical neurology and the second most common cause of dementia. Vascular factors leading to the development of hypoxia, oxidative stress, mitochondrial, endothelial dysfunction and, ultimately, to the development of apoptosis with the formation of degenerative brain changes are considered among the main risk factors for the development of CVD. The most important mechanisms of the development of TFR are hypoxia and oxidative stress, which indicate the need for the use of drugs with antihypoxant and antioxidant activity. Such drugs include Mexidol (ethylmethylhydroxypyridine succinate). Mexidol directly affects the pathogenetic factors of the formation of ischemic-hypoxic brain damage, has a high clinical efficacy in the treatment of various forms of cerebral circulatory insufficiency. Keywords: chronic cerebrovascular insufficiency, hypoxia, oxidative stress, vascular cognitive impairment, endothelial dysfunction, Mexidol.
Efficacy of Mexidol in patients with type 2 diabetes mellitus with neurological complications
Author:
E.L. PUGACHEVA
Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
Summary:
Objective. Complications of Diabetes mellitus (DM), depends on the severity of hypoxic tissue damage. Amelioration of hypoxic injury may improve current therapy approaches and enhance the quality of life in patient’s cohort suffered from DM. Material and methods. 30 pts which DM were enrolled into the study. Mexidol forte, was given IV 500 mg/day for 14 days, follow up with oral administration 250 TID. Clinical impression, neuropsychological scales and biochemical blood tests were recorded. Results. Mexidol administration improved cognitive functions, decreased the level of asthenia, depressia, improved sleep disturbances, and normalized biochemical landscape. Conclusions. Mexidol administration for the period 75 days may serve as important therapeutic supplementation and considered as adjunctive therapy in the treatment of patients with DM. Keywords: Diabetes mellitus, hypoxia, oxidative stress, antioxidants, neurotransmitters, antihypoxive medications, Mexidol.
The efficacy and safety study of Mexidol and Mexidol FORTE 250 in patients with chronic cerebral ischemia
Author:
L.A. SHCHEPANKEVICH1,2, YU.A. NIKOLAEV1, E.V. TANEEVA3, M.A. PERVUNINSKAYA1, M.S. SHCHEPANKEVICH1,2
1Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia;
3State Novosibirsk Regional Clinical Hospital, Novosibirsk, Russia
Summary:
Objective. To study the efficacy and safety of sequential MexidoL therapy, administered intravenously (500 mg once a day) for 14 days, followed by taking the oral form Mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days in elderly patients with chronic cerebral ischemia (CCI) on the background of arterial hypertension and atherosclerosis. Material and methods. An open prospective observational study included 60 patients with an established diagnosis (CCI), confirmed by the results of neuroimaging. All patients were examined with an assessment of neuropsychological status (MoCA test), severity of asthenia (scale MFI-20), emotional state (Hamilton anxiety and depression scale), motor functions (formalized clinical scale for assessing motor activity of elderly Tinetti). The effectiveness of the therapy was evaluated according to the quality of life questionnaire (SF-36). Results. The results of the study showed the high efficiency and safety of sequential therapy with Mexidol in relation to the relief of asthenic and emotional disorders, improving the state of cognitive functions, improving the quality of life of patients. The maximum effect occurred after the end of the full course of therapy. High adherence of patients to the therapy, low frequency of adverse events are shown. Conclusion. Sequential use of intravenous administration of Mexidol followed by oral administration of Mexidol FORTE 250 is an effective and safe way to treat patients with CCI. Keywords: chronic cerebrovascular disease, arterial hypertension, atherosclerosis, ethylmethylhydroxypyridine succinate, mexidol, mexidol forte 250, cognitive impairment.
Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO)
Author:
A.I. FEDIN1, V.V. ZAKHAROV2, M.M. TANASHYAN3, E.I. CHUKANOVA1, E.N. MADZHIDOVA4, L.A. SHCHEPANKEVICH5,6, O.D. OSTROUMOVA7
1Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia;
2Sechenov First Moscow Medical University (Sechenov University), Moscow, Russia;
3Scientific Center of Neurology, Moscow, Russia;
4Tashkent Pediatric Medical Institute, Tashkent, Republic of Uzbekistan;
5Novosibirsk State Medical University, Novosibirsk, Russia;
6Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Russia;
7Russian Medical Academy of Continuous Professional Education, Moscow, Russia
Summary:
Objective. To assess the efficacy and safety of sequential therapy with Mexidol solution for intravenous and intramuscular administration, 50 mg/ml and Mexidol FORTE 250 film-coated tablets, 250 mg in patients with chronic brain ischemia (CBI). Material and methods. An international multicenter, randomized, double-blind, placebo-controlled trial, conducted in 15 clinical centers located in Russian Federation and Republic of Uzbekistan, included 318 patients with CBI aged 40 to 90 years. The patients were randomized into 2 groups, the patients of the 1-st group received Mexidol intravenously 500 mg once daily for 14 days, followed by Mexidol FORTE 250 — 250 mg 3 times a day orally for 60 days; patients of the 2-nd group received a placebo in a similar mode. The primary endpoint was the mean value of difference by MoCA scale at the point of completing the therapy comparing to initial value. Results. According to the results of the assessment of the primary endpoint, statistically significant changes in the MoCA scores at the stage of completion of study were revealed when comparing the dynamics between the 1-st and 2-nd groups (p<0.000001). The lower limit of the 95% confidence interval for the difference in the average of the main efficacy endpoint between the 1-st and 2-nd groups was 1.51, which allows to state a higher efficacy of the use of Mexidol. According to the estimates of secondary endpoints, a statistically significant advantage over placebo at the last visit achieved while evaluation by the following scales and tests: digit symbol substitution test, MFI-20 asthenia assessment scale, Beck anxiety scale, Vane questionnaire, Tinetti scale, SF-36 questionnaire (mental component of health), CGI scale. The comparable nature of the safety profile of Mexidol and Placebo was established. Conclusion. The validity and expediency of the use of Mexidol and Mexidol FORTE 250 in the treatment of patients with CBI has been demonstrated. Keywords: chronic brain ischemia, cognitive impairment, neuropsychological testing, ethylmethylhydroxypyridine succinate, Mexidol, Mexidol FORTE 250, treatment of CBI, MEMO trial.
Features of responding to stress of elderly patients with chronic brain ischemia
Author:
T.A. SLYUSAR, YU.V. ABRAMENKO, S.S. RUBINA, R.V. MAYOROV, I.N. SLYUSAR
Tver State Medical University, Tver, Russia
Summary:
The aim of the study. To study the peculiarities of responding to stress, the stress resistance and adaptation of older men and women with chronic brain ischemia, as well as the stressboard effect of Mexidol. Material and methods. 124 patients aged 60–74 years old are surveyed: 72 men and 52 women (average age, respectively, 65.3 ± 0.4 and 64.7 ± 0.7 years) with Chronic Brain Ischemia I–II stage against the background of arterial hypertension and its combinations with atherosclerosis of cerebral vessels. The level of psychosocial stress was determined on the Holmes-Ray scale. Features of the response of patients to stress was studied using the methodology Scale of Psychological Stress PSM‑25 and S. Rogenzweig. Stress resistance was investigated using S. Kuhlen's stress resistance self-resistant test and Villianson. The level of anxiety was determined using a scale of Ch. D. Spilberger and Yu. L. Khanin, depressed – backup questionnaire. The type of adaptation reactions was studied in the leukocyte blood formula on the percentage ratio of lymphocytes and segmented neutrophils, taking into account the representation of other formed elements. Results. The level of stress in older women with Chronic Brain Ischemia was higher than in men. The predominance of the intrinsic orientation of the reaction to stress and resolving the type of response to men, and the extrapunitive or self-defense type among women, which may indicate the largerness of the latter. The level of stress resistance was lower in women than in men, which correlated with higher indicators of situational anxiety. Adverse adaptation reactions were more often registered in women than in men. The course of treatment with Mexidol of elderly patients with chemical leads to a decrease in the severity of subjective and objective symptoms, alarming disorders, increases the stress resistance and adaptive capabilities of the body, which is confirmed by an increase in the number of persons with favorable adaptation reactions. The high efficiency and safety of sequential therapy with Mexidol (injections, then the tableted form of Mexidol Forte 250) is shown. Keywords: chronic brain ischemia, sex, stress, stress resistance, emotional disorders, anxiety, depression, Mexidol, adaptation reactions.
The efficacy of antioxidant treatment with mexidol forte in 250 patients with chronic cerebral venous insufficiency
Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, KH.I. MAMAEVA
Pirogov Russian National Research Medical University, Moscow, Russia
Summary:
Objective. To study the efficacy and safety of complex treatment with 2-ethyl-3-hydroxy-6-methylpyridine (mexidol forte 250) and venotonic drugs L-lysine aescinat and diosmin/hesperidin in patients with chronic cerebral venous insufficiency (CCVI). Material and methods. One hundred and twenty CCVI patients with clinical and ultrasonic signs of cerebral venous discirculation were studied. Patients were stratified into group 1 (n=40) treated perorally with mexidol forte 250 and diosmin/hesperidin during 74 days in combination with two courses of L-lysine aescinat intravenously on the 1st and 30th days from baseline, group 2 (n=40) treated with mexidol forte 250 and diosmin/hesperidin during 74 days, group 3 (n=40) treated perorally with diosmin/hesperidin during 74 days. Results and conclusion. The efficacy and safety of the complex treatment of CCVI patients with venotonic drugs with the inclusion of mexidol forte 250 at a dose of 750 mg/day for 74 days is shown. The study demonstrates a significant positive effect of mexidol forte 250 on the dynamics of complaints and indicators of the neurological and psychoemotional status of patients. Monotherapy with the venotonic drug diosmin/hesperidin shows its insufficient efficacy. Keywords: chronic cerebral venous insufficiency, antioxidants, mexidol forte 250, venotonic drugs, L-lysine aescinat, diosmin/hesperidin.
Possibilities of improving the effectiveness of therapy in patients with chronic cerebral ischemia against the background of COVID-19
Author:
V.V. KOVALCHUK, I.I. ERSHOVA, N.V. MOLODOVSKAYA
Semashko City Hospital No. 38, St. Petersburg, Russia
Summary:
Objective. To study the possibility of improving the efficacy of treatment with mexidol in COVID‑19 patients with chronic cerebral ischemia (CCI). Material and methods. Three hundred and four patients with CCI and COVID‑19 were observed, group 1 (n=152) consisted of patients receiving basic therapy and mexidol, group 2 (n=152) received only basic therapy. Mexidol was administered intravenously for 14 days, 500 mg (10 ml) per 400 ml of saline solution, then Mexidol FORTE 250 was administered in a dose of 250 mg 3 times a day for 2 months. The state of cognitive functions (MoCA scale), sleep (Spiegel questionnaire), asthenia (MFI-20 scale), and quality of life (SIP questionnaire) were evaluated. Examinations were performed before treatment, 30 and 75 days after start of treatment. Results. In group 1, there was a more complete and earlier recovery of the state of cognitive functions (an increase in indicators on the MoCA scale, p<0.01), a regression of asthenia (p<0.05), and normalization of sleep (p<0.01). By the end of the study, there were significantly more patients in group 1 with complete or significant recovery of all quality of life indicators. Conclusion. Long-term sequential therapy with mexidol provides a more complete recovery of impaired functions in patients with CCI and COVID-19. Keywords: COVID-19, SARS-CoV-2, chronic cerebral ischemia, asthenia, cognitive disorders, dementia, quality of life, mexidol.