St.-petersburg,, Russian Federation

A Safety and Efficacy Study of Bevacizumab, Paclitaxel, Carboplatin Compared to Avastin® in Non-Small Cell Lung Cancer

Bevacizumab is a monoclonal antibody currently being developed by Mabscale LLC, as a proposed biosimilar to Avastin®, which is approved as first line treatment in combination with carboplatin and paclitaxel for patients with unresectable, locally advanced, recurrent or metastatic non-squamous Non-Small Cell Lung Cancer. This randomized equivalence study is designed to meet the regulatory requirement for approval of a biosimilar product.

CLL Therapy Approaches in Russia

Study of Alofanib in Patients With Metastatic Gastric Cancer

European CML Blast Crisis Register

Since the advent of treatment with tyrosine kinase inhibitors (TKI), the incidence of blast crises has significantly decreased. Nevertheless, about 5% of patients diagnosed with chronic myeloid leukemia (CML) will evolve into a blast phase at some point during the course of their disease. Furthermore, despite the advances made in CML treatment, outcome of patients with blast crises are still dismal. Due to the rarity of this condition clinical trials are challenging, and collaboration between researchers both at national and international level is needed to collect a meaningful number of data.

Efficacy and Safety of Cariprazine in the Treatment of Adolescent Participants (13 to 17 Years of Age) With Schizophrenia

Efficacy and Safety of Erenumab in Pediatric Participants With Episodic Migraine

This study is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of erenumab in migraine prevention in children (6 to <12 years) and adolescents (12 to <18 years) with episodic migraine. The trial consists of four phases: screening (up to 3 weeks of initial screening and a 4-week prospective baseline phase); the DBTP (24 weeks for Group 1 participants; 12-weeks for Group 2 participants) in which participants receive placebo or Erenumab dose 1, dose 2 or dose 3 (based on participant's body weight) via subcutaneous injection once a month; the optional dose level blinded extension phase (40 weeks), in which all participants are assigned to receive dose 1, dose 2 or dose 3 of Erenumab; and a 12 weeks safety follow-up phase (16 weeks after the last dose of investigational drug). The study intends to enroll 456 participants (376 adolescents and up to 80 children).

Chicago Classification Normative Metrics in a Healthy Russian Cohort According to High-resolution Esophageal Manometry

High-resolution esophageal manometry (HREM) is the current modality used to evaluate esophageal motility. There are 2 types of system: water-perfused system that is cheaper to maintain and a solid-state system that is considered to be more sensitive. According to the data obtained in the study of 400 patients and 75 controls by J Pandolfino et al it was proposed to use a common algorithm of HREM data interpretation and the normative values of the parameters used to interpret the color plots of HREM. This formed the basis for the first version of the currently used HREM reporting algorithm and classification of esophageal motility disorders called Chicago Classification (CC). To date, this classification has been updated several times by the International Working Group based on the recently published data. The Working group stated that the proposed normative values still need to be widely studied for each HREM system and in different populations. Some studies has been published recently on the normative values of HREM in different countries (predominantly in the US, in some European countries, Korea, India and China. But there has been no study on the subject in Russia still.

A Study of Etelcalcetide in Pediatric Subjects With Secondary Hyperparathyroidism and Chronic Kidney Disease on Hemodialysis

SHPT is a common and serious co-morbidity that develops relatively early in the course of CKD, worsens with declining kidney function, and is associated with serious complications in children on dialysis. Children on dialysis experience a wide spectrum of bone abnormalities and growth retardation, in addition to increased risk for cardiovascular morbidity and mortality that manifests early in their adulthood. Traditional therapies for SHPT (eg, vitamin D sterols) are widely used in the pediatric dialysis population, and have the potential to aggravate complications of the disease by increasing serum calcium (Ca), serum phosphorus, and serum Ca times serum phosphorus product. Etelcalcetide has been shown to be safe and efficacious in treating adult CKD patients with SHPT by simultaneously controlling intact parathyroid hormone (iPTH), Ca, and phosphorus and has recently been approved for use in adult patients with SHPT treated with hemodialysis in both the United States and Europe. Although no previous studies have been conducted in pediatric patients with etelcalcetide (one single dose pharmacokinetic [PK] study is currently ongoing),Amgen anticipates minimal to moderate risk with a possibility of direct benefit to the pediatric subjects (age 28 days to 18 years) in this study. The burden of complications of SHPT in the pediatric dialysis population and the limitations of current standard therapy, underscore the need for studies of etelcalcetide in these patients to address this unmet medical need and inform the pediatric nephrology community of the potential use of etelcalcetide in children on hemodialysis with critical safety and efficacy data.

Safety and Efficacy Study of Ftortiazinon in the Treatment of Patients With Complicated Urinary Tract Infections Caused by P. Aeruginosa

The study is divided into 2 phases. The course of treatment will be single (course of therapy with the drug/placebo under study) for a group consisting of three cohorts, and also single for a group of phase 2 participants (770 patients in total) consisting of two cohorts groups. The recruitment of patients to the second phase will commence after the evaluation of the data on safety and efficiency by the expert commission within the framework of reviewing the amendment to the current Study Protocol. At the second phase, it is proposed to study the optimal dosage chosen based on the results of the first (search phase) study. This study is aimed at evaluating the efficacy, safety and tolerability of the drug Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA), in comparison with placebo in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA), in the treatment of patients with complicated urinary tract infections (complicated UTIs) caused by P. aeruginosa. FIRST PHASE (search phase) At this phase, the patients will take the drug Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). According to the results of the screening of patients who have signed the Informed Consent Form, the patients are recruited in three groups with different doses of the drug. The total number of patients who received the drug or placebo will be at least 240 people according to the following scheme: Group 1 (80 patients) - Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) plus placebo. The drug is administered according to the following scheme on the first day: the first administration of Ftortiazinon 300 mg (1 tablet) plus placebo (1 tablet) 30 minutes after eating with lukewarm water, the second administration - 1 tablet (300 mg) after 12 hours, then within 6 days the drug is prescribed 1 tablet once a day plus 1 tablet of placebo (interval: 12 hours) 30 minutes after eating. Group 2 (80 patients) - Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation). The drug is administered according to the following scheme on the first day: the first administration of 600 mg (2 tablets) 30 minutes after eating with lukewarm water, the second administration - 1 tablet (300 mg) after 12 hours, then within 6 days the drug is prescribed 1 tablet twice a day at intervals of 12 hours. Group 3 (80 patients) - placebo in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). The drug is administered according to the following scheme on the first day: the first administration of 2 tablets 30 minutes after eating with lukewarm water, the second administration - 1 tablet after 12 hours, then within 6 days the drug is prescribed 1 tablet twice a day at intervals of 12 hours 30 minutes after eating. For all groups: Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). The drug is administered according to the following scheme: the drug with a dosage of 1.0 g is dissolved in 2.4 ml of sterile water for injection or 0.9% sodium chloride solution, or 0.5-1% lidocaine hydrochloride solution; then injected deep into the muscle, into the upper outer quadrant of the buttocks after pre-aspiration every 12 hours for 7 days*. SECOND PHASE (confirmation phase) The transition to this phase of the study to assess efficacy and safety of the drug Ftortiazinon will be carried out after selecting the optimal dosage according to the results of the first (confirmation phase) study. This transition will be carried out by making a corresponding amendment to the Study Protocol with the provision of data confirming the efficacy and safety of the selected therapeutic scheme. The assessment will be conducted according to the results of the 21-day surveillance for patients after completion of therapy with a drug/placebo. Group 1 patients will take the drug Ftortiazinon tablets 300 mg (FSBI "N.F. Gamaleya NRCEM" of the Ministry of Health of the Russian Federation) in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA) in accordance with the dosage regimen selected at the first phase. Maxipime® is a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). It is administered according to the following scheme: the drug with a dosage of 1.0 g is dissolved in 2.4 ml of sterile water for injection or 0.9% sodium chloride solution, or 0.5-1% lidocaine hydrochloride solution; then injected deep into the muscle, into the upper outer quadrant of the buttocks after pre-aspiration every 12 hours for 7 days. Group 2 patients will take placebo in combination with the drug Maxipime®, a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). Placebo is taken according to the scheme corresponding to those chosen at the first phase. Maxipime® is a powder for the preparation of a solution for intravenous and intramuscular administration of 1.0 g (Bristol-Myers Squibb, USA). It is administered according to the following scheme: the drug with a dosage of 1.0 g is dissolved in 2.4 ml of sterile water for injection or 0.9% sodium chloride solution, or 0.5-1% lidocaine hydrochloride solution; then injected deep into the muscle, into the upper outer quadrant of the buttocks after pre-aspiration every 12 hours for 7 days. Administration/injection of drugs Ftortiazinon/placebo and Maxipime® should be carried out simultaneously, preferably in one and the same time every day. Let the administration of Ftortiazinon/placebo will be for 30 min after administration of the drug Maxipime®. The duration of therapy with Maxipime® will be 7 calendar days; however, if the patient has no positive dynamics in the evaluation of clinical symptoms of complicated UTIs, there is an increase in uropathogen in the urine culture obtained on Visit 2, and the duration of therapy can be increased to a total of 14 calendar days.

The Role of Concomitant Diseases in Postoperative Complications Risk Stratification.

Advances in modern anesthesiology have significantly reduced the risk of anesthesia compared to the last century, however, the level of perioperative hospital mortality of planned operations at the moment is on average about 0.5% (ISOS group, 2016). Weiser et al. (2016) estimated that more than 313 million adults worldwide are subject to surgery each year. Thus, the number of deaths may result in several million each year worldwide. However, the study of the mortality risk is associated with certain difficulties, because over the past half century, this figure has decreased a hundred times and the study requires studies that include a large number of participants. Current research focuses on other outcome criteria - postoperative complications. Thus, anesthetic risk often refers to the risk of postoperative complications. The frequency of these complications varies in a wide range, ranging from 3 to 18 % (Gawande AA, 1999, Kable AK, 2002, Malik OS, 2018). The differences in the data are explained by the lack of clear definitions and differences in the design of studies, but the fact that the development of postoperative complications increases the risk of death several times (ISOS group, 2016) can be considered undoubted. However, despite the importance of this issue, in modern literature there is no clear idea of what is considered a high risk and which of the patients corresponds to this category. Understanding whether a patient is at high risk is an essential task - it allows you to obtain meaningful informed consent of the patient, as well as to understand whether to apply strategies for the prevention of complications (targeted infusion therapy, protective respiratory support, especially monitoring in the postoperative period, etc.). Attempts at preoperative risk stratification have been made for many decades, some scales estimate the initial physical status (ASA scale) (Young J, 2015) and predict mortality, others estimate the risk of specific complications (Lee index, respiratory risk scale, etc.) . Scales including intraoperative and postoperative parameters such as the POSSUM series of scales (Whiteley MS, 1996) are also being developed. The analysis shows that in routine clinical practice, these scales are not used very often, due to their limitations: subjectivity, technical complexity and often - low specificity and sensitivity. Concomitant diseases are the strongest predictors of postoperative adverse events and annual mortality. Monk et al. (2005) demonstrated that Charlson's comorbidity score of 3 or more significantly increased the risk of death. In addition, in most clinical studies, the ASAclassification of physical status as a kind of comprehensive assessment of patient comorbidity has repeatedly proved to be one of the strongest independent predictors of postoperative morbidity and mortality, despite the fact that this assessment is based on subjective perception (Watt J., 2018). The main concomitant diseases that are independent predictors of perioperative complications are diseases of the cardiovascular and respiratory systems (Van Diepen S, 2011). Increasing age, anemia, obesity, diabetes - these conditions also increase the risk of an adverse outcome. Diseases of the Central nervous system and neuromuscular diseases significantly disrupt the function of respiration, can change the level of the Autonomous regulation of the cardiovascular system, lead to significant cognitive disorders and nutritional deficiency, which also increases the risk of perioperative complications (Hachenberg T, 2014). On the other hand, large-scale observational studies conducted in recent years in a number of countries have not identified comorbidities as independent predictors of postoperative complications (Malik, 2018). Thus, data on the risk effects of comorbidities are contradictory and may be influenced by differences in the frequency and structure of these diseases in heterogeneous populations, as well as in different treatment strategies for cardiovascular, respiratory and other diseases. The identification of these risk factors is necessary to understand the pathophysiology of complications and identify potential ways to reduce anesthetic risk, such as the correction of concomitant disease. The degree of risk of surgery, of course, depends not only on the presence of comorbidities and their combinations, but also on the severity of surgical injury (Pearse RM, 2012, ISOS group, 2017), as well as the level of exposure to drugs for anesthesia and anesthetic techniques (Malik OS, 2018), therefore, the allocation of risk groups without these factors is also not appropriate. Objective: to assess the frequency and structure of comorbidities in patients undergoing surgery on the abdominal organs and to stratify the risk of postoperative complications by determining independent Evaluated parameters in study: 1. Age, gender; 2. Class of physical status by ASA; 3. The presence and type of concomitant disease; 3.1 CHD; 3.2 CHF; 3.3 Heart rhythm disorders; 3.4 COPD; 3.5 Bronchial Asthma; 3.6 CKD; 3.7 CNS diseases; 3.7.1 Stroke; 3.7.2 Epilepsy; 3.7.3 Parkinson's Disease; 3.7.4 Alzheimer's Disease; 3.8 Neuromuscular diseases; 3.9 Diabetes; 3.10 Anemia; 4 Treatment received by the patient; 4.1 β-blockers; 4.2 ACE Inhibitors; 4.3 Aldosterone antagonists; 4.4 Statins; 4.5 Anticoagulants; 4.6 Diuretics; 4.7 Bronchodilators; 4.8 Corticosteriods; 4.9 Insulin; 4.10 Anticonvulsants; 5. The type and severity of surgery ; 5.1 Open surgery on the organs of the upper abdomen; 5.2 Coloproctological operations; 5.3 Gynecological surgery; 5.4 Urological surgery; 5.5 Operations on vessels of the abdominal cavity; 5.6 Abdominal wall surgery; 5.7 Laparoscopic surgery; 6 Type of anesthesia; 6.1 Spinal; 6.2 Epidural; 6.3 Combined spinal-epidural; 6.4 Intravenous; 6.5 Combined; 6.6 General+epidural; 7. Integral scales; 7.1 The cognitive function of the Montreal scale ; 7.2 Respiratory risk ; 7.3 Lee's Cardiovascular Risk Scale ; 7.4 NSQIP Cardiac risk scale ; 7.5 Hepatic insufficiency according to MELD; 7.6 CKD Stage by Level of GFR and Albuminuria; 7.7 COPD degree by GOLD. Order of conduct 1. The data is registered in the Excel electronic database in a uniform format for all centers (the form will be sent by the coordinator to all centers participating in the study prior to the inclusion of patients). 2. All centers need to get approval by the local ethics committee before the start of the study. The study protocol will be registered in Clinicaltrial.gov. 3. The study includes all patients operated on within one operational day at the discretion of the center and meeting the inclusion criteria with registration in the questionnaire of the day of the week. 4. All patients could sign informed consent to participate in the study prior to inclusion in the study. 5. Before surgery, data on the patient and all studied factors specified in the study protocol are entered into the database. 6. All patients included in the study are monitored before discharge from the hospital with registration of the data specified in the protocol. 6. Every last day of the working week, all completed cases are sent as a separate Excel file to the study coordinator by email to trembachnv@mail.ru 7. The originals of the questionnaires are stored in the centers for the entire study time and for 3 years after its completion. 8. The summary database is formed by the study coordinator and provided to the centers after the end of the study. Statistical analysis The sample size was calculated taking into account the fact that at least 10 cases of postoperative complications per one factor included in the final regression model are required. Given the wide range of complication rates in previous studies (from 3% to 20%), we have chosen a lower bound for a more accurate assessment. To include 20 potential risk factors in the regression model, 200 cases of postoperative complications are required, which at a frequency of 3% is not less than 7000 people. Taking into account the risk of data loss, and taking into account as many potential risk factors as possible, the size of the required sample was increased to 12,000 people, which will also assess the contribution of comorbidities to certain groups of complications. For validation of predictive models will be recruited 4,000 additional. The inclusion of the patient in the main and validation group will be carried out randomly. The character of distribution of studied parameters will be evaluated using the criterion Kolmogorov-Smirnov. The continuous data will be presented as the median and interquartile range for the nonparametric distribution and as the mean and standard deviation for the parametric distribution. Categorical variables will be presented as the number of patients and a percentage of the total number of patients. For the initial assessment of the Association of the factor with postoperative complications, a single-factor analysis using the χ2 criterion and the Mann-Whitney test will be carried out. All variables with a reliable relationship identified in the univariate analysis (p less than 0.05) will be included in logistic regression if there is no collinearity between them (correlation coefficient less than 0.25). The logistic regression model will be constructed using a step-by-step reverse inclusion procedure in which the presence of a complication will be a dependent variable. Potential predictors will be removed if this exception does not cause a significant change in the log likelihood ratio. The criterion for excluding the factor will be set at the significance level of 0.05. Adjusted odds ratios and 95% confidence intervals will also be calculated. The resulting predictive model will be evaluated in the validation group using ROC analysis and the Hosmer-Lemeshov test.