Clinical Research Directory

Do QT-Prolonging Drugs Cause Major Adverse Cardiac Events in Hospitalized Adults?

There are 28 non-cardiology medications from multiple families costing more than $13 billion annually in Canada, categorized as 'Known' QT-prolonging medications (QTPmeds) based on very low levels of evidence. The association between many commonly used medications listed as known QTPmeds and actual major adverse cardiac events (MACE) is weak. Meanwhile, QTPmeds-related warnings are ubiquitous in every healthcare setting, triggering 'hard stop' disruption millions of times per day to front line clinicians. Poor quality medication safety alerts are increasingly recognized as a source of inferior patient care and provider burnout which detracts from healthcare sustainability. In this study, anonymized hospital electronic medical record data from more than 990,000 adult patients across Ontario will be used to compare patients who experience MACE with those who do not, measuring their real-time exposure to QT-prolonging drugs. Additionally, machine-learning techniques will also be used to find which patient or treatment factors best predict risk. The objectives of this study are to 1) Investigate whether exposure to one or more 'Known' QTPmed is associated with an increased risk of MACE after adjusting for confounders; and 2) Identify predictors and their relative importance for QTPmeds-associated MACE. In summary, QT-prolonging medications have the potential to cause very serious adverse events, including death. However, it is not sufficiently clear which patients under which circumstances suffer events, or when is QT prolongation a useful surrogate marker for harm. Meanwhile, ubiquitous medication alerts related to QT-prolonging medications are at best imprecise and at worst, misleading, costly and potentially dangerous. Now that data resources are available with the data elements, structure and sample size required to rigorously assess this association, this study will address this question to improve patient safety, provider satisfaction and the cost-effectiveness of care.

Effect of Hyperglycaemia and Moxifloxacin on QTc Interval in T2DM

Diabetes is a significant risk factor for sudden cardiac death, with the QTc interval on electrocardiograms (ECGs) often prolonged in diabetic patients due to factors such as hyperglycaemia and insulin resistance. Drugs like moxifloxacin can further exacerbate this effect, especially in those with diabetes. A previous trial on Type 1 diabetes suggested that hyperglycaemia and moxifloxacin have additive effects, prompting an investigation into whether similar effects occur in Type 2 diabetes (T2DM), particularly in individuals with high insulin resistance. This study aims to evaluate whether moxifloxacin-induced QT-prolongation is amplified by elevated blood glucose levels or insulin deficiency in T2DM patients, considering potential differences between sexes. Blood biomarkers will be analysed to understand the underlying molecular mechanisms. The trial will involve at least 24 male and female participants with insulin-resistant T2DM, aged 18 to 64 years, conducted at Richmond Pharmacology Ltd. Participants will receive treatments with glucose, moxifloxacin, and placebos while closely monitored for side effects during an inpatient stay, followed by outpatient appointments.