B.C.-led clinical trial points to safer care for critically ill patients

A B.C.-led clinical research team is behind a study that could help improve care for critically ill patients in intensive care units worldwide.

Researchers from Royal Columbian Hospital and Simon Fraser University have published findings in the Journal of the American Medical Association (JAMA), one of the world’s most recognized peer-reviewed medical journals.

The study, known as the CLiCK trial, examined central venous access devices, often called central lines, in adult intensive care unit (ICU) patients, and was presented by senior author Dr. Steven Reynolds at the American Thoracic Society International Conference on May 18th.

At issue are the catheters used to deliver fluids, medications, antibiotics and nutrition to the majority of critical care patients in hospital ICUs. While central-line care is essential for many of these patients, their use may lead to the risk for infection and functionality may be impeded by clotting in the catheter lumen. When one of the line channels is not being used, clinicians place a small amount of fluid (called a ‘catheter lock’) inside it to help keep the line open. A multi-centre clinical trial found that adding a 4% tetrasodium ethylenediaminetetraacetic acid (t-EDTA) locking solution was associated with a significant reduction in a composite measure of these complications.

The trial included 1,468 adult ICU patients at six Canadian hospitals: Royal Columbian Hospital, Surrey Memorial Hospital, Royal Jubilee Hospital, Nanaimo Regional General Hospital, St. Boniface Hospital and Burnaby Hospital. The trial was a triple-blind, multi-centre, cluster-randomized crossover trial designed to compare usual care with the study solution across busy ICU settings.

“This study tested a very practical question in ICU care: can we do more to keep central lines working safely for critically ill patients?” said Reynolds, associate professor in the Department of Biomedical Physiology and Kinesiology at SFU, a critical care physician at Royal Columbian Hospital, and executive lead of Royal Columbian Hospital Foundation’s Advancing Innovation in Medicine Institute (AIM).

“Central lines are essential for many ICU patients, but complications can interrupt care and result in additional treatment. Because these lines are used in ICUs around the world, evidence on how to reduce complications can matter beyond one hospital or one health system. The trial found a significantly lower rate in a clinically relevant composite outcome, driven most clearly by fewer catheter occlusions requiring alteplase. It gives clinicians and health systems around the world evidence to consider, while also pointing to questions that need further study.”

The study’s first author is Marlena Ornowska, whose work on this study was part of her PhD thesis completed at SFU’s Department of Biomedical Physiology and Kinesiology. She also holds a research associate position with AIM. Her doctoral work was central to the trial’s design, coordination and manuscript development.

"To me this has been an incredible experience, I feel so fortunate as a graduate student to have been involved in the cycle of this from the very beginning and to see it through," says Ornowska. "I’m so excited I had the immense privilege to work on something that is actually going to potentially make a difference in the lives of patients. I don’t think every grad student could say something like that." 

The primary outcome was a composite measure that included central line-associated bloodstream infection, catheter occlusion requiring alteplase and catheter removal due to occlusion. Alteplase is a medication used to help reopen blocked lines.

The composite outcome occurred at a rate of 13.1 events per 1,000 catheter-days in patients who received 4% t-EDTA, compared with 19.9 events per 1,000 catheter-days in the control group. In adjusted analysis, this represented a statistically significant 32 per cent reduction in the rate of these complications.

The difference was driven most clearly by fewer catheter occlusions requiring alteplase. No adverse events, serious adverse events or hypocalcaemia related to use of the study locking fluid were reported during the study period.

“Marlena’s work is impressive and reflects the role graduate researchers can play in working on clinical research teams to generate evidence that is directly relevant to patient care,” said Steve Robinovitch, professor and chair of the Department of Biomedical Physiology and Kinesiology. “Clinical research of this kind depends on rigorous methods, strong supervision and close collaboration with the health care teams delivering care. We’re proud of Marlena and Dr. Reynolds and everyone at his lab on this impactful study.”

Study activities were supported by a grant-in-aid and investigational product from SterileCare Inc.; funding from Royal Columbian Hospital Foundation and the BC Ministry of Health Innovation Pathway Program; Mitacs salary support for Dr. Ornowska; the CANTRAIN Doctoral Studentship Award; salary support for Dr. Reynolds through the TB Vets Charitable Foundation; support from Fraser Health’s Department of Evaluation and Research Services administrative team and clinical research units; and support for Dr. Reynolds by the Health Professional Investigator Awards from the Michael Smith Foundation for Health Research. Study funders had no role in study design, data collection, data analysis, data interpretation or writing of the report.

“Health technologies need to be tested in real clinical settings before health systems can make informed decisions about broader adoption. This study demonstrates the importance of bringing clinicians, health-care operators, funders and Canadian innovators together to address practical challenges in care delivery,” said Karen Mueller, CEO of SterileCare Inc., the manufacturer of KiteLock™ 4% Sterile Catheter Lock Solution used in the trial. “This work is also personal for me, given my family’s experience with central-line complications. The trial provides clinicians and health systems with peer-reviewed evidence to support better central-line management and improve quality of care for patients.”

“Clinical research in a hospital setting has to be rigorous, ethical and practical for the care teams delivering it,” said Kate Keetch, Fraser Health Director of Evaluation and Research Services. “This study reflects Fraser Health’s role in supporting research that begins with real questions from patient care and is tested through careful clinical methods. Research is a catalyst to continuous quality improvement and innovation in the health system, and this study is a shining example of how research is care.”

“Royal Columbian Hospital cares for some of the most critically ill and injured patients in British Columbia, and this study shows how questions that begin at the bedside can generate evidence with relevance beyond one hospital,” said Jeff Norris, President and CEO, Royal Columbian Hospital Foundation. “Through the AIM Institute, we are helping create the conditions for clinicians, researchers, and innovators to rigorously evaluate promising ideas in real-world care environments and generate the evidence needed to inform broader adoption across the health system.”