Mclennan, Canada

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 TAK-279 in Participants With Moderate-to-Severe Plaque Psoriasis

This study consists of 2 parts: Part A and Part B. Part A: Participants who did not participate in either parent study (TAK-279-3001 [NCT06088043] or TAK-279-3002 [NCT06108544]) may be enrolled and will be treated for up to 52 weeks. Participants who successfully complete Part A of the study are eligible to continue in Part B, but investigators must confirm their eligibility to continue in Part B. Part B: Participants who complete the treatment period of TAK-279-3001 (NCT06088043) or TAK-279-3002 (NCT06108544) parent studies or who complete Part A are eligible to enroll directly into open label extension treatment in Part B and will be treated for up to 156 weeks.

A Phase 3, Placebo-controlled, Double-blind Study Assessing Rocatinlimab in Prurigo Nodularis

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

NeuroCatch Reference Interval Database

Study specific Procedures: Includes a screen for eligibility and a scan visit. The total time 30 minutes to 1 hour for the whole study. The procedures can be completed on the same day or split between two days. Screening visit (15- 30min, virtual visit): Prior to any procedures being conducted, Informed Consent Form will be reviewed in detail, an opportunity will be given to decide to participate in the study or not and if all the study requirements are met as well as all the questions have been answered, consent form is signed. Participant study eligibility is reviewed including medical history, and brain scan requirements. If participant is eligible, scan visit will be completed. If participant is not eligible no further study procedures will be completed. Scan visit (15-30 min at the clinic): During the scan visit demographic information ( date of birth, sex, level of education, recent sleep, self-described mood, caffeine intake, alcohol consumption, nicotine usage, psychoactive usage, handedness, first language, profession and current medications) is collected, brain scan safety questionnaire is completed and a brain scan with NeuroCatch® Platform 2 will be completed. NeuroCatch scan procedure: A cap with the EEG sensors is placed on your scalp and will be adjusted to get good recordings of brain activity. An alcohol pad is used to clean the skin of your forehead, and a plastic syringe tip or wooden dowel to move your hair out of the way to place the EEG sensors/electrodes. A small amount of a conductive gel is applied under each electrode. This takes between 5-20 minutes. Once its all set up, you will be asked to listen to an auditory sequence that is 6 minutes long. During this period, you are asked to sit still and listen to the sounds and the words. Any information about you obtained from or for this research study will be kept as confidential as possible, All participants will be assigned a participant ID and data will identified using the ID.

Daptomycin Vs. Vancomycin for the Treatment of Methicillin Resistant S. Aureus Bacteremia

A Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Moderate to Severe Plaque Psoriasis

Pain Clinic Provides Public Health Safety

Chronic pain is associated with many behavioral or psychological disorders. The psychological disorders may have negative impact on the patient's social, economic, health, legal, domestic, relationship and employment situations. This prospective observational study evaluates the impact of pain management services on the patients' health, social, economic, and employment status. The clinical study explores the impact of pain clinic services on patients' mental health, childcare, family health, public health, road safety, addiction situation, public safety, injury rehabilitation, employment status and housing situation.

Small Steps for Big Changes - Healthy Cities Implementation Science

In partnership with YMCAs in Canada spanning 8 provinces (overseeing 44 distinct community facilities/sites), the investigators will adapt and deliver our evidence-based diabetes prevention program, Small Steps for Big Changes. The purpose of this project is to evaluate the implementation and effectiveness of SSBC across diverse urban communities. Specifically, the investigators aim to: 1. Evaluate the implementation and sustainability of the program by examining the number of staff trained/patients enrolled, attendance, sessions delivered as planned, delivery costs, and number of sites continuing to deliver the program. 2. Examine clinical-effectiveness of the program on: T2D status (self-report and HbA1c; primary outcomes), cardiorespiratory fitness, anthropometric (weight, waist circumference, resting heart rate), health behaviours (exercise, diet). 3. Examine cost-effectiveness of the program on: healthcare resource utilization, and health-related quality of life (secondary outcomes). Research Design: A hybrid type 2 implementation-effectiveness study design (Curran et al., 2012) with multi/mixed methods will be used to evaluate the implementation and effectiveness of SSBC. SSBC program: SSBC will be administered and facilitated by the community facility trainers at YMCA locations. SSBC consists of 6 sessions delivered over 4 consecutive weeks, with each session comprising brief (20-30 mins) counselling that support participants self-regulatory skills to promote independence and long-term adherence to healthy dietary behaviours and regular exercise, followed by 20-30 mins of supervised aerobic exercise.

Psychedelic-assisted Group Program for First Responders

All participants will undergo a 12-week, group-based program (one session per week, for 12 weeks). The first group session, as well as the Week 10 session will occur in-person. The remainder of the sessions will occur remotely. Each week, trained facilitators will help create a trauma-informed safe space for the group to thrive and promote cognitive resilience. The topics covered throughout the 12-week program include breath-work, mindfulness, self-compassion, embodiment, and Internal Family Systems work. During Week 10, participants will be provided with either psilocybin (active group) or complete a breathwork day (control group). For participants randomized to the active group, they will receive 10mg of psilocybin on Week 10. A clinician certified and trained in the therapeutic use of psilocybin will be on site for participants in the psilocybin group. During the dosing session, the clinicians will respond to whatever needs arise. This may include escorting them to the bathroom, giving them a drink of water. At least two staff (one facilitator and one clinician) will be on site during dosing days. The dose will be administered in clear capsules with approximately 500ml of water. Aside from the dose provided, the weekly session will continue as usual, with a focus on breath-work, embodiment, and gentle movement on dosing days. Psilocybin in the study comes in the form of the study drug, PYEX. PYEX is a drug substance which is a partially purified fraction of the extract of Psilocybe cubensis mushroom fruiting bodies. It is a mixture of indole alkaloids, other mushroom fruiting body components and stabilization excipients. The major indole alkaloids present include psilocybin and psilocin (dephosphorylated psilocybin). PEX010 is a capsule for oral administration and is manufactured with PYEX (12.5-14.0% psilocybin), excipients, and HPMC (hydroxypropyl methyl cellulose) capsules.