Tacna, Peru

Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML

This is a clinical trial to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 36 cycles) on the primary endpoint of overall survival (OS) in adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML). Participants will be tested for FLT3-ITD mutation status in a central laboratory using a validated assay.

AZD0486 as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL

This is a modular, Phase II, multicenter, single-arm, open-label study to evaluate the efficacy and safety of AZD0486 monotherapy administered as an intravenous (IV) infusion in participants with relapsed or refractory B-NHL. The purpose of this study is to determine the efficacy and safety of AZD0486 administered at the RP2D in adults 18 to 80 years of age with relapsed or refractory B-NHL.

Study of GS-2121 Given Alone or in Combination in Adults With Advanced Solid Tumors

A Platform Trial for Gram Negative Bloodstream Infections

BALANCE+ is an adaptive platform trial evaluating multiple treatment options in patients admitted to the hospital due to Gram negative bloodstream infections (BSIs). It focuses on both cross-cutting and subgroup-specific questions, using an open-label, pragmatic design embedded in routine care. BALANCE+ addresses the significant health concern of BSIs, which have high morbidity and mortality rates, exacerbated by the global public health threat of antimicrobial resistance (AMR). With rising resistance rates and limited new drug development, effective treatment strategies for BSIs remain under-researched. BALANCE+ follows the BALANCE trial, which evaluated duration of antibiotic treatment, and aims to further investigate critical questions in managing Gram-negative BSIs. This platform trial will explore various aspects of BSI treatment, including antibiotic de-escalation, oral antibiotic choices, central line management, treatment of specific pathogens, and the necessity of follow-up blood cultures. BALANCE+ is using Bayesian methods without a fixed sample size. Interim analyses will occur after every 1000th patient in each domain, and then for every 200th patient thereafter. The trial will stop if futility or superiority thresholds are met, or if a domain reaches its ceiling sample size (2500 patients for most domains and 4000 for the beta-lactam versus non-beta-lactam domain) without meeting a stopping threshold. A vanguard pilot trial involving over 150 patients at 9 hospitals across Canada confirmed the feasibility of the BALANCE+ trial. The main trial will include patients from the vanguard pilot phase since there has been no major change in the overall study design and domains. The adaptive design allows for interim analyses and adjustments by adding or removing domains as per the statistical analysis plan, enhancing the trial's efficiency and relevance.

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

Low-value Care, and Variation in Practice for Children Hospitalized With Bronchiolitis

Background: Low-value care is defined as the use of a health service, such as diagnostics and treatments, for which the harms or costs outweigh the benefits. Reducing low-value care is important in improving the health of Canadians and achieving a sustainable, high-quality healthcare system. Bronchiolitis is among the most common and most costly causes of hospitalizations in children. Most healthcare costs associated with bronchiolitis are related to hospitalization, and these costs have been increasing. Supportive care is recommended by national guidelines for the treatment of bronchiolitis, and many commonly used diagnostics and treatments in bronchiolitis are considered low-value, making it a great model to study low-value care in pediatrics. To develop effective interventions to reduce low-value care, and ensure the right resources go to the right patient at the right time, it is crucial to develop a better understanding of inpatient management of bronchiolitis in Canada. The goal of this prospective multi-site observational study is to analyze the use of 6 low-value healthcare services in children diagnosed with bronchiolitis, their costs, and measure the variability in practice of these services. Specific objectives: Among infants admitted with bronchiolitis at 15 Canadian hospitals with pediatric admissions, to: 1. Measure the incidence, patterns, and predictors of use of 6 low-value care health services and their costs in children hospitalized for bronchiolitis, namely 1) respiratory virus testing; 2) chest x-rays; 3) continuous pulse oximetry; 4) short-acting beta-agonists; 5) systemic corticosteroids; and 6) antibiotics; 2. Estimate the extent of practice variation in the use of 6 low-value health services between hospitals; 3. Determine whether differences in use of low-value health services are associated with patient and family characteristics (e.g., race and ethnicity, socioeconomic status, language), and whether these contribute to disparities in care. Design: A multi-centre (n=15), prospective observational cohort study of children hospitalized with bronchiolitis. Data will be obtained from medical charts and entered into a central, web-based REDCap database. A health equity questionnaire will be completed by participants once during their child's admission and then again 30 days later to inquire on additional medical care required post-admission. Secondary outcomes and covariates will also be collected which include but are not limited to duration of ICU stay, use of mechanical ventilation, cardiac arrest, length of hospital stay, disease severity, clinician years of experience, and death. Analysis of the primary outcome will be descriptive for each low-value health service, overall and stratified by sex. Costs of hospitalization will be assessed from a healthcare institution perspective. Cost of each of low-value health service will be described and compared between one another and across sites to identify key differences which may be targets for process change. This study will provide important data to understand the use of low-value care in bronchiolitis treatment in Canada, and will inform our approach to addressing low-value care in bronchiolitis and in other common conditions.

The STRIVE Before Surgery Trial

Background: The number of people presenting for surgery, and their risk profile, are increasing. People presenting for surgery face substantial risk of postoperative adverse events. Fifteen to 30% of patients suffer a serious medical or surgical complication after surgery, and 1 in 5 develop a new patient-reported disability that reflects a loss of independence in day-to-day life. More than 1.4 million inpatient surgical procedures are performed in Canada each year. Globally, >300 million surgical procedures occur annually. As an increasing number of people present for surgery, the average risk profile of this population is rising. Surgical patients are typically older and live with comorbidity. This means that strategies to improve patient outcomes and reduce resource utilization are urgently needed. Patients, the public, clinicians, and policy makers participating in 2 separate James Lind Alliance Priority Setting Partnerships (Canada & UK) identified prehabilitation as a Top 10 priority for perioperative research. Furthermore, prehabilitation is currently discussed in the popular media as a strategy to improve outcomes for the growing number of high-risk patients presenting for surgery. Overarching Aim: The pilot phase evaluated three pragmatic elements (recruitment, adherence, and follow-up) that our experience in prehabilitation research demonstrate are necessary to support successful, large-scale evaluation. Data from the pilot phase will be combined with this full-scale trial. The full-scale trial will evaluate patient reported disability at 30 days after surgery. Methods: Design, setting and participants: The STRIVE Before Surgery Trial is an assessor blinded multicenter individual patient parallel-arm vanguard pragmatic randomized controlled trial. People => 18 years old having inpatient abdominal, thoracic, pelvic, head-and-neck or vascular surgery with expected length of stay of => 2 days will be included. Intervention: The intervention includes 3 aspects (exercise, nutrition and breathing). Our intervention is a home-based multimodal prehabilitation program supported through an online platform. Outcomes and sample size: Primary outcome is patient-reported disability 30 days after surgery. Secondary outcomes are days at home in the 30 days after surgery, survival, health-related quality of life, length of stay, patient safety indicators, intensive care unit admission, non-home discharge, readmission, emergency department visits, health system costs, and elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial using the Theoretical Domains Framework. Our trial sample size calculation is informed by parameter estimates from the pilot phase. A sample of 902 patients (451 per arm) will provide 90% power to detect a 5% minimally important difference between the mean WHODAS scores using an F-test from an Analysis of Covariance (ANCOVA) at the two-sided 5% significance level. We conservatively assumed a common standard deviation of 23 (equal to the upper limit of the 95% CI observed in our vanguard trial) and a correlation with baseline of 0.3. We also allowed for up to 10% attrition. Expertise: The team features multidisciplinary clinical and methodological experts, nationally representative knowledge users and patient representatives. Expected outcomes: Despite systematic review findings that exercise prehabilitation may improve physical performance and function, limitations exist that preclude generalizability, including many identified studies being high or unclear risk of bias and single center studies with <100 participants. The investigators aim to conduct this low risk of bias, mutli-center study of adult surgical patients >18 years to address this gap.