Drug-Induced Sudden Death & Ventricular Arrhythmia

To investigate the relationship between the use of prescription drugs and the occurrence of ventricular arrhythmia and sudden death.

Study Overview

• Status: Completed
• Conditions: Heart Diseases; Cardiovascular Diseases; Death, Sudden, Cardiac; Ventricular Arrhythmia

Detailed Description

BACKGROUND:

Drug-induced sudden cardiac death (also called sudden death, SD) and ventricular arrhythmia (VA) have arisen as major public health concerns in the last decade. Sudden death/ventricular arrhythmia have resulted in the withdrawal of more drugs in recent years than any other adverse drug reaction, and the identification of over 100 non-cardiac drugs as suspected of being high-risk. Unfortunately, controlled studies measuring the risks associated with specific drugs are very few in number, presumably because of the complexity of such studies and the massive sample sizes needed to study this outcome. Even studies in "large" databases have lacked adequate statistical power for crucial subgroup analyses. This lack of controlled data on clinical sudden death/ventricular arrhythmia has necessitated reliance on uncontrolled observations and on studies of putative markers of risk such as QTc prolongation in the electrocardiogram. However, the utility of uncontrolled observations is always subject to question, and the validity of these putative markers remains unknown. As a result, clinicians, patients, regulators, and drug manufacturers are ill-equipped to address the critical clinical and public health decisions concerning drug-induced sudden death/ventricular arrhythmia.

DESIGN NARRATIVE:

This study will compile a massive new pharmacoepidemiologic database of Medicaid data (linked with Medicare data for those enrolled in both programs, and with the Social Security Administration Death Masterfile) from five large Medicaid programs. This will be combined with the UK General Practice Research Database. This combined database will be used to conduct a series of nested case-control and case-crossover studies to measure the absolute and relative rate of all-cause death and sudden death/ventricular arrhythmia (SD/VA) associated with five of the most commonly used drug classes of greatest concern: antipsychotics, antidepressants, opioid analgesics, quinolone antibiotics, and macrolide antibiotics. A multi-stage investigative strategy will be used: Stage 1 will compile the database, assure its quality, and reproduce known associations. Stage 2a will compare drugs among the classes of interest. Stage 2b will use the case-crossover design to look for associations controlling for stable patient factors. Stage 2c will examine the effect of dose and inhibitors of pharmacokinetic clearance, the functional equivalent of high-dose use. Stage 3 will develop predictive indices to stratify patient subgroups receiving high-risk drugs.

• Study Type: Observational
• Enrollment (Actual): 31000000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Medicaid enrollees from CA, FL, NY, OH and PA combined with the UK General Practice Research Database.

Description

This combined database will be used to conduct a series of nested case-control and case-crossover studies to measure the absolute and relative rate of all-cause death and sudden death/ventricular arrhythmia (SD/VA) associated with five of the most commonly used drug classes of greatest concern: antipsychotics, antidepressants, opioid analgesics, quinolone antibiotics, and macrolide antibiotics.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All cause death	All data years

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite outcome of sudden death and ventricular arrhythmia	All data years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Sean Hennessy, PharmD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: January 21, 2005
• First Submitted That Met QC Criteria: January 21, 2005
• First Posted (Estimate): January 24, 2005

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Arrest; Heart Diseases; Cardiovascular Diseases; Death; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Death, Sudden
• Other Study ID Numbers: 1287; 5R01HL076697 (U.S. NIH Grant/Contract)