Reviews on Recent Clinical Trials - Volume 14, Issue 3, 2019

Background: Data management is an important, complex and multidimensional process in clinical trials. The execution of this process is very difficult and expensive without the use of information technology. A clinical data management system is software that is vastly used for managing the data generated in clinical trials. The objective of this study was to review the technical features of clinical trial data management systems. Methods: Related articles were identified by searching databases, such as Web of Science, Scopus, Science Direct, ProQuest, Ovid and PubMed. All of the research papers related to clinical data management systems which were published between 2007 and 2017 (n=19) were included in the study. Results: Most of the clinical data management systems were web-based systems developed based on the needs of a specific clinical trial in the shortest possible time. The SQL Server and MySQL databases were used in the development of the systems. These systems did not fully support the process of clinical data management. In addition, most of the systems lacked flexibility and extensibility for system development. Conclusion: It seems that most of the systems used in the research centers were weak in terms of supporting the process of data management and managing clinical trial's workflow. Therefore, more attention should be paid to design a more complete, usable, and high quality data management system for clinical trials. More studies are suggested to identify the features of the successful systems used in clinical trials.

Background: Advances in the development of Direct-Acting Antivirals (DAAs), particularly pangenotypic drugs, have led to a high rate of hepatitis C virus (HCV) eradication. Notably, real- world studies have confirmed the efficacy and safety of pangenotypic DAA combinations reported in registration trials. The aim of this study was to review the treatment recommendations, and the efficacy and safety data of anti-HCV pangenotypic drugs reported in registration clinical trials and in recent real-life cohort studies. Methods: We reviewed the efficacy and safety data of pangenotypic anti-HCV drug combinations reported in original articles and in online conference abstracts. Results: Current pangenotypic drug combinations resulted in very high rates of sustained virologic response and few adverse reactions in real-life settings. SVR12 rates in real-life studies ranged from 90-100% depending on the pangenotypic combination, the HCV genotype and the stage of liver disease. Most adverse reactions reported in real-life settings were mild in intensity and rarely led to treatment discontinuation. These results are in accordance with those of clinical trials. Conclusion: Pangenotypic DAAs result in very high rates of sustained virologic responses and are well tolerated. However, they are contraindicated in patients with decompensated cirrhosis or advanced chronic kidney disease who failed previous DDA-based treatment. Further research is required to customize treatment to “unpackage” current DAA combinations and to develop generic drugs against HCV.

Background: Domino transplant occurs when a recipient explanted graft is used for a second recipient. Introduction: The first experience came from thoracic surgery by the observation that many patients during heart-lung transplantation actually showed a functional heart that could be employed in other subjects with a good result. Results: This concept was then extended to the field of liver transplantation. At present, some patients transplanted for an inborn metabolic disease may be considered as excellent domino liver donors. Conclusion: The results, limitations, clinical challenges and the donor and recipient features of domino liver transplantation are discussed in this manuscript.

Background: The 20th century represents a breakthrough in the transplantation era, since the first kidney transplantation between identical twins was performed. This was the first case of tolerance, since the recipient did not need immunosuppression. However, as transplantation became possible, an immunosuppression-free status became the ultimate goal, since the first tolerance case was a clear exception from the hard reality nowadays represented by rejection. Methods: A plethora of studies was described over the past decades to understand the molecular mechanisms responsible for rejection. This review focuses on the most relevant studies found in the literature where renal tolerance cases are claimed. Contrasting, and at the same time, encouraging outcomes are herein discussed and a glimpse on the main renal biomarkers analyzed in this field is provided. Results: The activation of the immune system has been shown to play a central role in organ failure, but also it seems to induce a tolerance status when an allograft is performed, despite tolerance is still rare to register. Although there are still overwhelming challenges to overcome and various immune pathways remain arcane; the immunosuppression minimization might be more attainable than previously believed. Conclusion:. Multiple biomarkers and tolerance mechanisms suspected to be involved in renal transplantation have been investigated to understand their real role, with still no clear answers on the topic. Thus, the actual knowledge provided necessarily leads to more in-depth investigations, although many questions in the past have been answered, there are still many issues on renal tolerance that need to be addressed.

Background: Inadequate response to Erythropoietin Stimulating Agents (ESA) despite using relatively larger doses regimen represents a potential risk factor of Cardiovascular (CV) related mortality in addition to health-care economic problems in anemic patients with Chronic Kidney Disease (CKD). Erythropoietin (EPO) hyporesponsiveness related to inflammation has been increased progressively. Melatonin is well known as a potent anti-inflammatory agent. Therefore, the current study was designed to evaluate whether melatonin could improve anemic patients response to EPO. Methods: This single controlled clinical study was carried out in 41 CKD patients with hemoglobin (Hb) levels less than 11g/dl divided randomly in a 1:1 ratio into 2 groups; treatment group who received 5mg melatonin plus their regular treatments and control group who received their regular treatments only. Hematological and iron status parameters include Hb level, serum iron (S. iron), Transferrin Saturation Ratio (TSAT) and serum ferritin (S. ferritin) in addition to inflammatory parameters that include tissue necrotic factor alfa (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) determined before and after 12 weeks of treatment. Results: Melatonin remarkably increases the Hb level with a significant increase in S. iron and TSAT compared to baseline. The elevation of S. iron and TSAT was significantly higher in the melatonin group. Additionally, all inflammatory markers estimated were reduced significantly by melatonin compared to base line and control group. Conclusion: The results of the current study showed that melatonin has an advantageous effect on improving EPO response in anemic patients with CKD.

Background: The present study examined the efficacy of the walking program on biochemical parameters among the elderly women. Methods: A total of one hundred elderly women participated in this randomized clinical trial study. The intervention group attended a 24-week walking exercise meeting five times per week. The control group continued with their routine activities. The subjects were assessed in Fasting blood glucose (FBS) and lipid profile before and after 12 and 24 weeks of the program. Results: The mean age of the elderly participants in the study was 68.33 ± 4.55 years. The results of repeated measures ANOVA showed a significant difference between the intervention and the control group in FBS, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol after completing the program (for all p < 0.001). Conclusion: The low-cost physical activity intervention could be effective for reducing chronic vascular disease risk factors among community-dwelling elderly women.

Background: Pruritus is one of the most common and disabling symptoms of liver disease such as Primary Sclerosing Cholangitis and Primary Biliary Cholangitis. Cholestyramine, rifampin, opioid antagonists, antihistaminic agents and SSRIs are used for the management of pruritus. Due to rifampin drug interactions as well as its serious side effects such as hepatotoxicity, clinicians are endeavoruing to find a safer and a more effective substitution. Objective: The purpose of this study was to compare the efficacy and safety of sertraline with rifampin in the management of cholestatic pruritus. Methods: In a single-blinded randomized clinical trial a total of 36 patients of PSC and PBC were divided into two equal groups, one group received 100 mg/day sertraline and the other group received rifampin 300 mg/day for 4 weeks. Visual analog scale was used to record pruritus severity at baseline and 4 weeks after drug intervention, also, ALT, AST, ALP and total bilirubin of all patients were measured at three different time points. Results: Over the follow-up period, pruritus had relieved in both groups, but there was no significant differences between sertraline and rifampin in pruritus management (pvalue=0.740), also there was no significant difference between the two intervention strategies (A versus B) in total bilirubin level (pvalue=0.106). Moreover, the ALT, AST and ALP levels were found to be significantly different between the two groups (Pvalue#130;0.01). Conclusion: There is no difference between sertraline and rifampin in pruritus improvement, but sertraline has less adverse effects on hepatobiliary enzyme levels, so it seems to be safer than rifampin.

Background: Inductive reasoning relies on an infinite regress without sufficient factual basis and verification is at any time vulnerable to single contrary observation. Thus, appraisal based on inductive verification, as applied in current clinical trial appraisal scales, checklists or grading systems, cannot prove or justify trial validity. Discussion: Trial appraisal based on deductive falsification can identify invalid trials and give evidence for the recommendation to exclude these from clinical decision-making. Such appraisal remains agnostic towards corroborated trials that pass all appraisal criteria. The results of corroborated trials cannot be considered more robust than falsified trials since nothing within a particular set of complied trial criteria can give certainty for trial compliance with any other appraisal criterion in future. A corroborated trial may or may not reflect therapeutic truth and may thus be the basis for clinical guidance, pending results of any future trial re-appraisal. Conclusion: Trial grading following appraisal based on deductive falsification should be binary (0 = Invalid or 1 = Unclear) and single component scores should be multiplied. Appraisal criteria for the judgment of trial characteristics require a clear rationale, quantification of such rationale and empirical evidence concerning the effect of trial characteristics on trial results.