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

NCT07374263 | Recruiting

• 1 other identifier: CIHR grant # PJT-197768
• Study Type: observational
• Target: 990,000
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Acquired Long QT; Syncope; Ventricular Arrhythmias; Torsades de Pointes; Medication Safety; MACE

Keywords

Medication safety; QT interval prolongation; Long QT syndrome; Ventricular arrhythmia; Torsades de pointes; Major adverse cardiac events

Outcome Measures

Primary Outcomes (1)

• Composite of major adverse cardiac events (MACE)

  Time to first MACE during hospitalization, defined as incidence of any of the following: Mortality, non-fatal cardiac arrest, ventricular arrythmia including torsades de pointes, and syncope

  From first exposure to the end of hospitalization, which would typically be up to 4 weeks follow-up.

Secondary Outcomes (4)

• Overall Mortality

  From first exposure to the end of hospitalization, which would typically be up to 4 weeks follow-up.

• Non-fatal cardiac arrest

  From first exposure to the end of hospitalization, which would typically be up to 4 weeks follow-up.

• Ventricular arrhythmias

  From first exposure to the end of hospitalization, which would typically be up to 4 weeks follow-up.

• Syncope

  From first exposure to the end of hospitalization, which would typically be up to 4 weeks follow-up.

Study Arms (2)

Exposed (Known QTPmeds)

Exposed to a known QTP medication

Unexposed (no known QTP meds)

No exposure to a known QTP medication

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This is a retrospective observational study using de-identified electronic-medical-record data from St. Joseph's Healthcare Hamilton and GEMINI hospitals; no direct participant enrollment or consent is required.

You may qualify if:

• Adult patients 18 years of age or older
• Admitted to St. Joseph's Healthcare Hamilton or GEMINI hospitals between December 2017 and March 2025

You may not qualify if:

• Patients \<18 years old
• Outpatient encounters

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead
• McMaster University: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (2)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 1Y3, Canada

RECRUITING

GEMINI

Toronto, Ontario, M5B 1T8, Canada

RECRUITING

MeSH Terms

Conditions

Torsades de Pointes; Syncope; Long QT Syndrome; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Tachycardia, Ventricular; Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Anne M Holbrook

  St. Joseph's Healthcare Hamilton

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne M Holbrook, MD,PharmD,MSc,FRCPC

CONTACT

905-522-1155; cptres@mcmaster.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Director, Division of Clinical Pharmacology and Toxicology, McMaster University

Study Record Dates

• First Submitted: December 6, 2025
• First Posted: January 28, 2026
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 28, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)