529. Systematic Review and Meta-Analysis of Ivermectin Safety Profile in COVID-19 Trials

Background There is a continued and pressing need for safe and effective treatment of COVID-19. Significant survival benefits have been shown by dexamethasone, tocilizumab and sarilumab, however they are only recommended in hospitalised COVID-19 patients. Ivermectin is a well-established and readily available antiparasitic drug which may be suitable for treatment in mild and moderate disease stages. It recently demonstrated anti-viral properties in vitro and now over 80 clinical trials have been registered worldwide to test its effectiveness in COVID-19 patients. This meta-analysis aims to collect data on adverse events reported in new COVID-19 treatment trials for the use of ivermectin as a repurposed medication. Methods Data was extracted from randomised trials of COVID-19 treatment trials identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. The primary outcome of this meta-analysis is the frequency of adverse events. Key safety events included serious, gastrointestinal, neurological, cardiovascular and dermatological adverse events. Results Overall, 18 trials investigating ivermectin for COVID-19 in a total of 2496 participants reported safety data and were included. There was no significant difference in the proportion of all adverse events between ivermectin and the comparator. There were 371/1261 (29%) adverse events recorded in the ivermectin containing arms and 376/1284 (29%) in the control arms (RR 1.02 [95% CI 0.77 - 1.34]; p = 0.91). There was no significant difference in the rate of serious adverse events across treatment arms (RR 1.95 [95% CI 0.75 - 5.11]; p = 0.18). No significant differences between ivermectin and the control were seen across different subcategories of adverse events. Figure 1 shows a summary of the results for all adverse events. Forest plot comparing ivermectin and the control for all adverse events in COVID-19 trials, subdivided into single-day dosing trials and multi-day dosing trials. Conclusion The results of recent COVID-19 trials show that overall, ivermectin is safe and well-tolerated. No significant difference in adverse event reporting was found across all subgroups in single and multi-day treatment regimens for the studies analysed. Safety reporting methodologies often varied across trials. Future and ongoing trials should be encouraged to collect and monitor safety data systematically. Disclosures All Authors: No reported disclosures

Nationally representative estimates of the participation of cancer patients in clinical research studies according to the commission on cancer.

74 Background: The successful conduct of cancer clinical trials hinges on the willingness of patients to participate. The rate of adult clinical trial participation has been regarded as being < 5%. However, national estimates of trial participation are nearly two decades old, and no evidence based on original data sources has been examined for many years. Moreover, studies about trial participation have focused solely on enrollment to treatment trials, which does not reflect the willingness of patients to contribute to other key elements of clinical research, such as quality of life or biorepository studies. We determined inclusive, contemporary estimates of clinical trial participation for adults with cancer using a national sample of data from 1,200 institutions. Methods: The data were from the Commission on Cancer (CoC), a consortium of cancer-related organizations providing accreditation for both academic and community cancer care facilities across the U.S. CoC enrollment data represent 70% of all cases of cancer diagnosed each year. Deidentified, institution-level aggregate counts of annual enrollment to treatment, biorepository, diagnostic, economic, genetic, prevention, quality of life, registry, and screening studies were examined. Overall, study-type estimates for the period 2013-2017 were estimated. Multiple imputation by chained equations was used to account for missing data, with summary estimates calculated separately by type of program (e.g., NCI-designated cancer programs) and pooled. Results: Across the entire U.S. system, the estimated participation rate to cancer treatment trials was 6.3%. Enrollment to treatment trials was highest at NCI-designated comprehensive cancer centers (18.9%), while for community cancer programs (CCPs) and comprehensive CCPs, treatment trial rates were 4.4% and 3.6%, respectively. Nearly 1 in 7 patients participated in biorepository studies (13.4%), including 39.4% at NCI cancer centers. Patients participated in a wide variety of other study types, including registry (8.1%), prevention (6.4%), genetic (3.6%), quality of life (2.9%), economic (2.7%), diagnostic (2.7%), and screening studies (1.8%). At least 25.4% of adult cancer patients were estimated to participate in one or more cancer clinical research studies. Conclusions: In a first-time use of nationally representative enrollment data from the CoC, enrollment to cancer treatment trials was 6.3%, higher than historical estimates of < 5%. Patients participated in a diverse set of other study types, and taken together, at least one quarter of patients participated in a study. Contributions of adult patients with cancer to clinical research is much more comprehensive than previously understood.

Recent SIV-Macaque Trials: A Reassessment of Immune Priming and Varying Infectability in Repeated Low-dose Challenge Studies

Nowadays, most preclinical HIV treatment trials use a protocol of administering repeated low-dose challenges (RLCs) of simian immunodeficiency virus (SIV) to macaques. Statistical analyses of treatment efficacy under the RLC protocol need to consider two confounding hypotheses, both pertinent biologically to HIV: (1) the non-infecting challenges may immunize animals against SIV; and (2) the animals may vary in intrinsic infectability (“frailty”). To explore the two hypotheses, a previous study (Regoes 2012) assembled a database from 7 articles with SIV-macaque treatment trials. With two explicable exceptions, Regoes concluded that the control data did not support either confounding hypothesis. Recent SIV-macaque trials present opportunities to evaluate the conclusions’ robustness. Accordingly, the present article assembles from 24 articles an updated database containing net survival curves from both control and treatment arms in SIV-macaque treatment trials. Broad patterns of statistical significance (at p <0.05, uncorrected for multiple testing) made it difficult to dismiss the confounding hypotheses completely in the controls. Although statistical analysis has focused on defense against variable frailty, only one set of controls showed significant variable frailty, whereas many sets showed significant immunization. As trials progressed, changes in the probability of infection per challenge were significant in 8/28 trials (1/3 trials using oral challenges; 2/4 trials using vaginal challenges; and 5/21 trials using rectal challenges). The results suggest the possibility that vaginal challenges may immunize animals faster than rectal challenges, and they also bear on previous conclusions that repeated exposure to HIV without treatment may have no effect on infectability or may even reduce it.

Bulletin of Clinical Studies in Q1 2021

Purpose. To evaluate clinical trials data since January 2021 till March 2021. Materials and methods. The information about clinical trial’s approvals from the state register of medicines of Russian Federation ministry of health website was used as the main source of the original data concerning clinical trials. The register contains all the information relating to clinical trials in Russian Federation. Results. Clinical trials data was analyzed by its type (international, local, bioequivalence), sponsorship (foreign, local), phases and disease areas. Separately COVID-19 clinical trials were considered. Conclusion. During the 2021 Q1 we can mark a clinical trail’s quantity growth (started ones) both in Russia and in Moscow in comparison with 2018-2020 similar periods, that is definitely a positive trend especially in COVID-19 pandemic circumstances. There is a significant growth of bioequivalence share in 2021 versus 2019-2020 in Moscow. Due to SARS-CoV-2 ongoing pandemic lots of related to SARS-СоV-2 treatment clinical trials started, which considerably increased the contagious diseases pool in clinical trials market structure. Totally 14 related to SARS-СоV-2 treatment trials started in Russia, including 5 ones held in Moscow Healthcare Department medical organizations.