Reviews on Recent Clinical Trials - Volume 11, Issue 4, 2016

Introduction: Atherothrombosis and coronary artery disease affect more than 13 million individuals only in the United States, about 8 millions in Europe and are the major causes of death worldwide. In particular chronic stable angina impairs patient quality of life, is associated with an important health spending and increased patient mortality; it is a prominent symptom of coronary artery disease (CAD), the latter being prevalent worldwide in patients. A key role in pathophysiology of cardiovascular acute events is played by activated platelets. Aspirin and adenosine diphosphate antagonist in addition to it is recommended for 1 year for reduction of cardiovascular events in patients with prior myocardial infarction with a weak recommendation to continue thereafter. P2Y12 receptor antagonists, in addition to aspirin, have been shown in the last years, to reduce ischemic events in patients with acute coronary syndrome but their role in secondary prevention is still new and unclear. The aim of our paper is to review the long-term effect of therapy with ticagrelor on the basis of recent evidence based data. Methods: We performed an online search on the major search engines. All the randomized controlled trials were summarized in the table. Results: We included in our paper six randomized controlled trials and we mentioned about ten post – hoc analysis, sub studies and registries. All studies included the type the therapy and a mid or long term clinical follow up. Conclusions: The studies reported in our paper and in particular PEGASUS – TIMI 54 study showed the merit to placing attention of prevention secondary ischemic events after acute coronary syndrome in the context of treatment with dual anti – platelet therapy; it proved a clinical benefit in patients treated with ticagrelor (60 mg x 2) for 3 years. Nevertheless, the effectiveness of these results cannot be generalized to patients with higher bleeding risk or low ischemic risk. In fact prolonged therapy with ticagrelor 60 mg in combination with aspirin could be considered valuable in patients with repeated acute ischemic events or with several coronary revascularizations over time (especially in patients with lower bleeding risk).

The casual relationship concerning Human papillomaviruses (HPV) and cervical cancer is already established. Therefore, such HPV-associated malignancies might be prevented by prophylactic HPV vaccines. From 2009, two prophylactic HPV L1 Virus-Like Particle vaccines namely, Gardasil® - quadrivalent (Merck) and Cervarix™ - bivalent (GlaxoSmithKline) are widely commercially available. By Aug 2014, 58 countries had introduced HPV vaccination in their national immunization program; this has led to numerous publications on safety and real world effectiveness. We have also seen long-term immunogenicity and efficacy data emerging. Data on cross-protection has also evolved. In clinical trials, it is observed that vaccinating adolescents results in higher immunological response than young adults hence to achieve best HPV vaccine efficacy it is advisable to immunize before the onset of sexual activity. Recently we have seen development of 2 dose vaccine schedule for adolescent, and emerging evidences even point that single dose of HPV vaccines can result in high efficacy, this observation is currently under consideration but if accepted will greatly impact vaccination coverage. In terms of safety, pregnancy registry did not find any unexpected patterns in fetal or maternal outcomes. This review only focuses on the efficacy and safety data of both Food and Drug Administration approved vaccines from clinical phase I to phase IV.

HIV/AIDS was once a highly deadly infective disease that killed the global people of a million annually two decades ago. While we are enjoying the HIV therapeutic advances (mostly important from HAART invention), one obvious drawback is still unresolved—unable to clearance all HIV from infected human bodies. As a result, a series of different therapeutic attempts have been proposed based on present knowledge of different features of HIV-induced pathogenesis and human mortalities. Facing this shortcoming, innovative designs and update of HIV vaccines and other types of HIV therapeutic inventions can be a final solution for completely HIV clearance and infection managements in human beings. Owing to these scientific and medical significances, several experimental and clinical attempts have to be made. Among these attempts, part of them (updating HIV vaccine developments and clinical routines) are quite promising and noteworthy. In this article, we offer the general information of this attempt and discuss it separately, especially on the respects of HIV vaccine strategic innovations.

Introduction: Non-Small Cell Lung Cancer (NSCLC) is an aggressive malignancy with poor overall survival that accounts for up to 85% of lung cancer diagnoses. The use of immunotherapy in the form of checkpoint inhibition, to enhance the immune system’s ability to attack malignant cells, has been a promising addition to treatment options in advanced NSCLC. Results: Such therapeutic agents aimed at the Programmed Death 1 (PD-1) receptor or Programmed Death Ligand 1 (PD-L1) have revealed promising results against many types of cancer including NSCLC. Examples of these agents include nivolumab, pembrolizumab, BMS-936559, atezolizumab, and MEDI4736, of which the first two are approved by US FDA in the second line treatment of advanced NSCLC. Discussion: Impressive improvements in objective responses from PD-1 blockade were found in both first line therapy as well as treatment after progression on platinum based therapy. In addition, the safety profile is favorable with significantly lower grade 3-4 adverse events compared to standard of care. The optimal selection criteria and factors that show an increased response to therapy are still being determined.

Background and Rationale of Study: The real-life data of triple therapy-based treatment in patients with chronic hepatitis C were investigated in this survey of 12 clinical centers of southern Italy. This retrospective study analyzed data from 176 consecutive patients. Methods: 125 (70%) patients were treated with telaprevir, and 51(30%) with boceprevir. There were no differences in demographic characteristics between the groups. The degree of Liver Fibrosis (LF) was evaluated according to Liver Biopsy (LB) and/or Transient Elastography (TE). 53/176 patients (30%) had liver cirrhosis. Sixteen patients (9%) were treatment naïve, and the remaining were not: 92 were non-responders (52, 84%), 63 relapsed (35,79%), and 5 discontinued treatment (2, 8%). Results: Overall, the rapid Virological Response (RVR) rate was 67.6%. Of the 103 patients who had follow-up for at least 12 weeks after the end of treatment, 61 (59, 2%) achieved a Sustained Virological Response (SVR). According to multivariate analysis for SVR, RVR was the only independent predictive factor of SVR, irrespective of the degree of LF and the type of response to previous treatments. In telaprevir-treated patients, the rate of RVR was similar in patients with F0-F2, F3 and F4 fibrosis (85%, 84%, 78%, respectively), and the SVR rates among RVR patients was similar irrespective of LF. Conclusions: Data from this real-life study confirm the efficacy reported in clinical trials, although cirrhosis appears to play a smaller role in influencing treatment efficacy. Moreover, RVR is the only independent predictive factor of response regardless of cirrhosis. Based on RVR and for patients with cirrhosis, a shorter therapy might be considered, at least with telaprevir-based therapy.

Background: To assess the role of docetaxel plus androgen deprivation in metastatic, hormone-sensitive prostate cancer. Methods: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing docetaxel plus androgen deprivation with androgen deprivation alone in patients with metastatic, hormone-sensitive prostate cancer were considered eligible and included into the analysis. Results: Six papers (3 randomized clinical trials, and 3 systematic reviews with meta-analysis) were considered eligible and included into the analysis. A significant improvement in time to progression and OS in the entire population treated with docetaxel plus androgen deprivation was reported in all the trials and meta-analyses, and in two trials and all meta-analyses, respectively. One trial reported improvement of OS only in patients with high volume disease, and the meta-analysis that also analyzed the subgroups of patients with high or low volume disease reported a benefit of docetaxel plus androgen deprivation for either the entire population or the two subgroups of patients. Conclusion: The early use of docetaxel combined with androgen deprivation improves the main outcomes in the treatment of metastatic, hormone-sensitive prostate cancer. The available data suggest that docetaxel plus androgen deprivation could be considered the novel standard for fit patients with metastatic, hormone-sensitive prostate cancer.

Background: Many people seek alternative treatments to reduce stress and to manage anxiety. To counsel people appropriately, physicians need to understand current evidence and recognize both the value and defects in the facts. Objective: To review the effect of Tai Chi interventions on improvement of mental health and to learn lessons from current evidence through various clinical studies. Methods: A literature search was performed to identify research studies that assessed Tai Chi’s mental health benefits. Selected studies were classified according to research design, outcome measures, and results. They were qualitatively assessed based on Tai Chi’s significant influence on mental health in the areas of mood, stress, and anxiety level. Results: After screening in citations that mentioned Tai Chi as an intervention, we found 21 clinical studies, all of which included at least one outcome measure of mental health or a testing system that included a mental health component. Our results show low evidence of recommending Tai Chi intervention to all patients who seek improvement in mental health despite that many positive effects of Tai Chi practice on mood and anxiety were found in different clinical trials. Conclusion: Considering the fact that Tai Chi is a gentle exercise, well suited for people with various physical capabilities, especially the elderly, health care providers may consider recommending it to people with mental health issues and seek alternative treatment besides routine medical care. Nonetheless, clinicians should be aware of the limitations due to incomplete understanding of Tai Chi as an intervention. Better evidence and stronger clinical trial designs are needed to further investigate Tai Chi’s role in improving mental health.

Chronic Kidney Disease (CKD) is an important public health problem throughout the world. The effects of exercise training are unclear in patients with CKD. This review aimed to evaluate the effects of exercise training to delay the progression of CKD and which training style is most effective. We developed individualized search strategies for the National Library of Medicine including the PubMed MeSH database to June 2015. We searched articles related to exercise training and kidney disease using the terms “CKD”, “renal disease”, “renal insufficiency”, “renal failure”, “end-stage renal disease (ESRD)” and “physical therapy”. We searched only for reports in English and for full free papers. We also chose papers based on the references in the papers obtained by the search. Our search identified 6 different trials including 131 participants. Our review of these 6 studies suggests that aerobic exercise training may improve exercise capacity, and resistance training may also improve muscle function in patients with CKD. No cardiac events were reported in any of the published exercise training studies reviewed, suggesting the safety of exercise in patients with CKD.

Objectives: To identify the knowledge and attitudes of community pharmacists towards upper respiratory infections. Setting: The pharmacists, who participated in an annual clinical pharmacy congress in Tehran, were enrolled in this study. Intervention: We conducted a cross-sectional descriptive study to assess the knowledge and attitudes of 72 community pharmacists towards upper respiratory infections (URI) using a questionnaire. Main Outcome Measures: We investigated the knowledge and attitudes of pharmacists towards rational antibiotics use in URI in Iran. Also we tried to detect causes of irrational antibiotic use. Results: The response rate of our study was 72%. Of all respondents, 98.61% answered the knowledge question” inappropriate use of antibiotics could lead to drug resistance and would increase drug allergy” correctly. More than half (55.56%) of the community pharmacists believed that pharmacists can be affected by patients’ expectations for antibiotics prescription. A majority of pharmacists gave a correct response to questions about beneficial use of corticosteroid in URI (90.28%) and symptoms persistent after 10-14 days even with antibiotic therapy (86.11%). More than half of all pharmacists had misconceptions on antibiotic use for URI in children under 2 years old. More than half of all pharmacists believed that most cases of URI are viral infections. Also, 90.28% of all pharmacists believed that guidelines for antibiotics prescribing may be beneficial in appropriate antibiotic use. Conclusion: According to a high response rate for the question about efficiency of antibiotics prescription guidelines, reliable information on the appropriate use of antibiotics should be more widely available for pharmacists.

Background & Objective: We aimed to identify the signals that indicate the possible benefits of administering Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) at the initiation of meal, compared to immediately after food. Methods: This was a randomized, controlled, pilot study in 160 patients who received only NSAIDs for various pain conditions. Patients were randomized to Group I (control group) –NSAID After Food (AF), Group II–NSAID Before Food (BF), Group III–NSAID BF for 2 days and then crossed over to AF for next two days (CO-1) and Group IV–NSAID AF for 2 days and then crossed over to BF for next two days (C0-2 group). Group III & Group IV were given a washout period of 48 hours after the initial two days of treatment. All were followed up for the next 2 drug free days. Patients were observed for the development of gastritis (epigastric distress, epigastric pain, nausea, fullness of stomach, repeated reflux) throughout the study. Results: Symptoms of gastritis were seen in 6.45% (2/31) and 36.11% (13/36) patients in group I and II, respectively. There was no statistically significant difference in the development of gastritis in AF group. However, statistically significant difference (P<0.05) was found between BF group and AF intake of NSAIDs [CO-1 (AF), CO-2 (A.F), AF (control group)] in terms of development of gastritis. Interpretation & Conclusion: Administering NSAIDs at the initiation of meal is better tolerated as indicated by the lower incidence of gastritis. If proved in larger population, routine concurrent administration of medication for prevention of gastritis can be avoided.