Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00102180 |
| Other study ID # |
1287 |
| Secondary ID |
5R01HL076697 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2005 |
| Est. completion date |
November 2008 |
Study information
| Verified date |
December 2020 |
| Source |
University of Pennsylvania |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
To investigate the relationship between the use of prescription drugs and the occurrence of
ventricular arrhythmia and sudden death.
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.
