The study, published in The New England Journal of Medicine, highlights the power of a new clinical trial framework implemented at Sinai Health, which allows for large-scale randomized clinical trials (RCTs) in general hospital wards.
The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial revealed that seven days of antibiotic treatment is sufficient for the treatment of bloodstream infections, caused by bacteria growing in the blood. These findings have the potential to reduce length of stay in hospital, reduce the spread of antibiotic resistance, and enhance healthcare efficiency globally.
The trial was led by Sunnybrook Health Sciences Centre with Mount Sinai Hospital as a key site. Drs. Michaal Fralick, a general internist, and Michael Detsky, an intensive care unit physician, served as site leads for Sinai Health,
Advancing clinical trial methodology
Historically, patients on general medicine in-patient units were not the focus of randomized clinical trials, and often, trials funded by pharmaceutical companies, rarely extended to general ward patients. This changed during the COVID-19 pandemic, when physicians at Sinai Health, led by Dr. Fralick, championed a novel approach to trials by recruiting participants from the general inpatient population.
“We had to come up with a solution so that when the next patient with COVID-19 comes into our hospital, there will be clinical trials available to them and access to potential medications to treat their COVID-19,” said Dr. Fralick, who is also a Clinician Scientist at Sinai Health and an Associate Professor at the University of Toronto’s Institute of Health Policy, Management and Evaluation.
This innovative model enabled Sinai Health to join global efforts to test COVID-19 treatments, which led to the discovery of life-saving treatments and informed patient care globally. Ultimately, its success paved the way for participation in non-COVID-19 trials like BALANCE.
"The ability to run these trials is a testament to the dedication of physicians, nurses, and staff who embraced additional responsibilities and secured funding through competitive grants," Dr. Fralick explained. His leadership in reshaping clinical trial practices helped to earn him the Gairdner New Investigator Award for 2024.
Results that save lives and resources
The BALANCE trial, involving 3,608 patients, showed that a seven-day antibiotic course is as effective as a 14-day regimen in preventing deaths and infection relapses, while also reducing unnecessary antibiotic use and associated risks like gut infections and antibiotic resistance.
“This is truly a landmark trial that will change practice in all areas of inpatient care—surgery, obstetrics, ICU and others,” said Dr. Jennie Johnstone, an infections diseases physician, Medical Director, Infection Prevention and Control (IPAC) at Sinai Health and Division Director for Infectious Diseases in the Department of Medicine at the University of Toronto. While Dr. Johnstone was not involved in the BALANCE trial, she played a key role in establishing the new clinical trials framework at Sinai Health.
Dr. Johnstone continued, “It highlights the critical need to conduct these trials to challenge current practices and explore whether there are better alternatives. This trial also demonstrates the importance of conducting trials in the general medicine ward population, which is an area often overlooked, and it wouldn’t have been possible without the foundational work we did during COVID-19."
Shorter antibiotic use also reduced hospital stays, offering profound benefits for both patients and healthcare systems worldwide.
Empowering the next generation of researchers
Sinai Health’s role in advancing clinical trial methodologies extends beyond research. Recognizing the importance of fostering future clinical leaders, Dr. Fralick established a course to train medical and nursing students in the complexities of running clinical trials and has been joined by Dr. Johnstone and Dr. Vanessa Allen, and infectious diseases physician and medical microbiologist. These trainees played a vital role in patient recruitment for BALANCE, gaining hands-on experience that prepares them to lead future innovations.
"Education is a cornerstone of our research mission," Dr. Johnstone noted. "By equipping the next generation of researchers with practical skills, we ensure the sustainability of these advancements."
A vision for the future
The success of the COVID-19 and BALANCE trials demonstrates the feasibility of conducting large, international clinical studies that incudes patients recruited from the general ward at Sinai Health, a model made possible by the dedication of Sinai Health clinicians and staff. By addressing logistical challenges and expanding trial scope, they have laid the groundwork for more inclusive and impactful research.
Several large international trials are already underway at Sinai Health that include the general inpatient population. BALANCE +, a continuation of BALANCE asking additional questions to optimize treatment of patients with bloodstream infections caused by gram-negative bacteria, A-DONUT is investigating the use of antibiotics in order adults with delirium, while SNAP is evaluating treatments for Staphylococcus aureus, a bacterium that causes bloodstream infections that was excluded from BALANCE because it requires distinct clinical management.
"Our new framework allows us to answer important clinical questions that improve outcomes not just for our patients, but for patients worldwide," said Dr. Fralick.
