Redcliffe

Researchers are evaluating different treatment strategies for patients hospitalized with Gram-negative bloodstream infections (GN BSIs) through the BALANCE+ trial. This adaptive platform trial uses an open-label, pragmatic design embedded in routine care to address important questions in managing GN BSIs, including antibiotic treatment duration, antibiotic de-escalation, oral antibiotic options, central line management, specific pathogen treatment, and follow-up blood cultures. The study builds on previous research and aims to improve patient outcomes and reduce antimicrobial resistance, a growing global health concern. The trial includes multiple treatment comparisons, such as de-escalation versus no de-escalation of antibiotics, oral beta-lactams versus non-beta-lactams, central vascular catheter retention versus replacement, cephalosporin versus carbapenem for low-risk AmpC organisms, and routine follow-up blood cultures versus no routine follow-up. Treatments are tailored based on blood culture results and clinical decisions, with specific protocols for antibiotic switching and catheter management. The trial uses Bayesian methods with interim analyses after every 1000 patients initially, then every 200 patients, and stops domains based on predefined criteria or sample sizes. Participants are patients admitted to hospitals with confirmed Gram-negative bacteremia who meet eligibility criteria for each domain. Assessments include monitoring for death, reinfection, readmission, and new antimicrobial resistance over 90 days, measured by the Desirability of Outcome Ranking (DOOR) scale. The trial incorporates detailed inclusion and exclusion criteria and collects data through routine clinical care, ensuring ongoing evaluation of treatment effectiveness and safety throughout the study period.

Researchers are evaluating the use of non-vitamin K oral anticoagulants (NOACs) compared to no anticoagulation in people who have experienced transient atrial fibrillation episodes triggered by stress and have additional risk factors for stroke. This multinational, investigator-initiated Phase 4 trial aims to prevent stroke and other serious cardiovascular events in this group by assessing the effects of NOACs on two main outcomes: the occurrence of non-hemorrhagic stroke or systemic embolism, and a combination of vascular death and other major cardiovascular problems, over a follow-up period lasting until the last participant reaches 24 months of observation. Participants in the study are randomly assigned to either receive one of several NOAC medications—edoxaban, apixaban, dabigatran, or rivaroxaban—with dosing adjusted as needed and chosen by their prescribing doctor, or to receive no oral anticoagulation. The treatment continues throughout the follow-up period. The trial is open-label, meaning both researchers and participants know which treatment is given. The study specifically focuses on patients who had transient atrial fibrillation related to stress, such as after certain surgeries or acute medical illness. During the study, participants undergo regular monitoring to track the incidence of stroke, embolism, vascular death, heart attacks, blood clots, and other cardiovascular events. Researchers collect information over up to two years to evaluate these outcomes. Safety and adherence to treatment are also monitored. This thorough follow-up helps determine the impact of NOAC treatment compared to no anticoagulation in this particular patient population.

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 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.

Blood cultures are blood tests used to detect infections, but collecting these samples can be challenging due to contamination and insufficient blood volume. This research evaluates whether using the PIVO Pro, a needle-free blood collection device that draws blood through an existing peripheral intravenous catheter (PIVC), reduces contamination compared to the standard blood collection method. The study focuses on adults aged 18 and older in emergency departments who require blood cultures to check for bloodstream infections. Participants will be randomly assigned to two groups: one using the PIVO Pro device to collect blood samples through the PIVC, and the other using the usual blood draw method. The PIVO Pro device advances a flexible tube through the catheter to obtain a fresh blood sample, potentially avoiding contamination and reducing the need for additional needles. The trial includes 1,148 adult participants across three emergency departments. During the study, participants will receive standard care, and researchers will collect information about blood sample collection and culture results from medical records. The main outcome measured is the success of blood culture draws without contamination, assessed at baseline. Additional measures include blood sample fill volume and quality, antibiotic use, and catheter-related complications. There is also a sub-study at one site focusing on catheter failure and vessel changes after blood draws.

Researchers are investigating treatments for bloodstream infections caused by the bacterium Staphylococcus aureus, which can be deadly within three months of infection. This international, multi-center Phase 4 adaptive platform trial evaluates multiple treatment options simultaneously to identify those that reduce death rates within 90 days of infection. The trial adapts over time by assigning more patients to better-performing treatments, removing less effective ones, and adding new options, aiming to find the best combination of therapies for patients with this serious infection. Participants receive various antibiotic treatments such as Cefazolin, Penicillin, Clindamycin, Vancomycin or Daptomycin, as well as strategies like early switching to oral antibiotics. The trial also includes whole body FDG PET/CT imaging using standardized protocols to support diagnosis and treatment decisions. Patients are randomly assigned to different concurrent treatment options currently used in routine care, with ongoing adjustments based on accumulating results. During the study, participants undergo regular evaluations including blood culture monitoring to confirm infection clearance, clinical assessments, and imaging when applicable. Researchers track all-cause mortality up to 90 days after enrollment as the primary outcome. The trial infrastructure supports additional sub-studies, with patient safety and treatment effectiveness closely monitored throughout the trial period.