Clinical trial NCT00102180: Drug-Induced Sudden Death & Ventricular Arrhythmia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiovascular Diseases
Death, Sudden, Cardiac
Heart Diseases
Ventricular Arrhythmia
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2005-01-24
Enrollment: 31000000
Sex: ALL
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Medicaid enrollees from CA, FL, NY, OH and PA combined with the UK General Practice Research Database.

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: All cause death
timeFrame: All data years
Secondary outcomes:
measure: Composite outcome of sudden death and ventricular arrhythmia
timeFrame: All data years
Other outcomes:
Locations:
Study officials:
affiliation: University of Pennsylvania
name: Sean Hennessy, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: