Dubbo

Researchers are evaluating the effect of a triple therapy inhaler called BGF MDI containing budesonide, glycopyrronium, and formoterol fumarate compared with a dual therapy inhaler called GFF MDI containing glycopyrronium and formoterol fumarate in people with Chronic Obstructive Pulmonary Disease (COPD) who have a higher risk of heart and lung problems. This Phase III randomized, double-blind, parallel group study takes place at multiple centers and focuses on cardiopulmonary outcomes in these patients. Participants receive either the BGF MDI 320/14.4/9.6 micrograms twice daily or the GFF MDI 14.4/9.6 micrograms twice daily. The treatments are inhaled using metered dose inhalers. The study compares these two therapies over time to see how they affect the time until the first severe heart or lung event occurs. The study design ensures that neither participants nor researchers know which treatment is given to reduce bias. During the study, participants will have regular visits to the study site or virtual visits to complete assessments. Researchers will monitor lung function, symptoms, and blood tests, including blood eosinophil counts and COPD assessment test scores. The main outcome measured is the time to the first severe cardiac or COPD event, with follow-up lasting up to three years. Safety and adherence to treatment will also be closely observed throughout the study period.

Researchers are evaluating whether fluid therapy using Plasma-Lyte48 compared to 0.9% sodium chloride can increase the number of days alive and days out of hospital by day 28 for critically ill patients with moderate to severe diabetic ketoacidosis (DKA) admitted to emergency departments and critical care areas. This phase 3, blinded, cluster crossover randomized controlled trial addresses the rising incidence and hospital admissions for DKA, aiming to provide definitive evidence to guide optimal fluid resuscitation. The study responds to current gaps in evidence and variability in DKA management protocols across hospitals in Australia. The trial involves 20 Australian hospitals participating in two 12-month intervention periods separated by a one-month gap. Each hospital uses either Plasma-Lyte48 or 0.9% saline as the blinded fluid therapy during the first period, then switches to the alternate fluid in the second period. Both fluids are supplied and labeled to preserve blinding, and clinicians administer the fluids based on standard clinical endpoints for up to 72 hours or until discharge from critical care. Additional treatments like glucose-containing solutions, bicarbonate, and electrolyte supplements are given as needed under clinician discretion. Participants will be monitored through the critical care stay and contacted by telephone at day 28 to assess outcomes. The main measurement is hospital-free days within 28 days after enrollment. The study also involves end-user representatives in all stages, ensuring consumer perspectives in protocol design and dissemination. This comprehensive approach aims to clarify the best fluid treatment for moderate to severe DKA and improve patient care and health outcomes.

Researchers are conducting LOCATOR, a multicenter phase II randomized clinical trial, to evaluate the quality of contouring in radiation treatment for breast cancer patients. The study compares artificial intelligence (AI) assisted contouring using the locally developed LOCATOR software with fully manual contouring done by radiation oncologists. The goal is to determine if AI-assisted contouring is as good as manual contouring and if it can save time for radiation oncologists. Participants are randomly assigned in a 3:1 ratio to receive either AI-assisted contouring or fully manual contouring. The AI model is initially trained on contours from 45 previous breast cancer cases and is updated regularly with new patient data. The AI generates initial contours automatically, which are then reviewed. The study also compares geometric accuracy, dosimetric differences, and economic factors between AI-assisted and manual contouring. Participants must be 18 years or older with primary breast cancer and able to consent. Researchers assess contour quality using the MD Anderson Contouring Grade Scale over 18 months, along with geometric and dosimetric evaluations. Safety and performance data are collected throughout the study, which includes ongoing updates to the AI model based on patient results.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.

Researchers are evaluating the safety, effectiveness, and pharmacokinetics of pumitamig (BNT327) combined with chemotherapy and other investigational agents in adults with first-line non-small cell lung cancer (NSCLC). The study includes two substudies based on NSCLC histological subtypes due to differences in chemotherapy treatments. This Phase 2/3, multisite, randomized, open-label trial aims to assess treatments in participants with advanced NSCLC who have not previously received systemic treatment. Each substudy has a Phase 2 part where participants are randomly assigned to one of two doses of pumitamig combined with chemotherapy drugs such as pembrolizumab, carboplatin, pemetrexed, or paclitaxel, given intravenously. The Phase 3 part will include independent data monitoring and blinded central review of tumor scans for all treated participants. The overall planned duration per participant is up to 64 months, covering both study parts and follow-up. Participants will undergo regular tumor assessments and monitoring for safety, including recording treatment-emergent adverse events, dose changes, and serious side effects up to 90 days after the last dose. Effectiveness will be measured by tumor response rates, changes in tumor size, and progression-free survival, with tumor imaging reviewed by a blinded independent committee. This long-term study involves careful evaluation of treatment impact and participant health over approximately five years.

Researchers are investigating the effects of opevesostat compared to alternative treatments abiraterone acetate or enzalutamide in people with metastatic castration-resistant prostate cancer (mCRPC). This phase 3, randomized, open-label study focuses on participants who have already been treated with next-generation hormonal agents and taxane-based chemotherapy. The study aims to assess overall survival (OS) in participants with and without androgen receptor ligand binding domain (AR LBD) mutations, hypothesizing that opevesostat may improve survival. Participants will receive either oral opevesostat or an alternative hormonal agent such as abiraterone acetate or enzalutamide. Additional supportive medications like hydrocortisone, fludrocortisone acetate, prednisone, or dexamethasone may be given orally or as needed. The study compares these treatments directly during the trial period. Throughout the study, participants will provide tumor tissue samples and undergo regular assessments including imaging scans, laboratory tests, and performance status evaluations. Researchers will monitor overall survival for up to approximately 54 months, differentiating outcomes based on AR LBD mutation status. Safety and treatment effects will be carefully tracked during this time to evaluate the benefits and risks of the treatments.