In this study we will study the incidence of QTc-interval prolongation when combinations of 2 or more QTc-prolonging drugs are prescribed. Also we will investigate if QTc-prolongation is more frequent in patients with higher drug plasma…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the incidence of prolonged QTc-interval during use of
all combinations of QTc-interval prolonging drugs
Secondary outcome
1. Are drug concentrations in patients with clinically significant prolongation
of the QTc-interval higher compared to patients without prolongation of the
QTc-interval?
2. For the pharmacogenetic analysis we will compare the presence of variant
alleles, as dichotomic variabele, in both groups with the *2-test.
Background summary
The QTc-interval on the ECG represents the duration of the action potential in
the ventricle plus the repolarisation-time. Subjects with a prolonged
QTc-interval have an increased risk for heart rhythm disturbances and acute
cardiac death. There are more than 50 drugs that prolong the QTc-interval,
some of which have been withdrawn from the market.
The exact risk of QTc-prolongation with simultaneous use of 2 or more
QTc-prolonging drugs is unknown. Possibly there are synergistic effects,
resulting in an increased risk with drug combinations. Genetic risk factors may
further contribute to the risk of QTc-prolongation.
With the introduction of an electronic prescription system in the ErasmusMC we
can now easily identify all patients using combinations of 2 or more
QTc-prolonging drugs. The physician receives an automatic alert when
prescribing such combinations, that are mostly ignored, as scientific evidence
for handling these alerts is not available.
Study objective
In this study we will study the incidence of QTc-interval prolongation when
combinations of 2 or more QTc-prolonging drugs are prescribed. Also we will
investigate if QTc-prolongation is more frequent in patients with higher drug
plasma concentraties, or in patients that are identified as *poor
metabolisers*.
The goal is to develop guidelines to handle interaction-alerts, by quantifying
the risk of presecribing combinations of QTc-prolonging drugs. This may lead
to improved drug safety for patients in the Erasmus MC.
Study design
Prospectieve cohort study, including all patients in whom a combination of 2 or
more QTc-interval prolonging drugs is prescribed.
In the hospital pharmacy all drug interactions that could lead to QTc-interval
prolongation are screened. The responsible pharmacist or clinical
pharmacologist farmacoloog, after consultation of the treating physician, will
approach the patient for participation in this study.
After obtaining informed consent an ECG will be made and blood will be sampled
for pharmacokinetic and for pharmacogenetic analyses.
Study burden and risks
ECG monitoring and a single vena puncture form a minimal risk for the patient
Postbus 2040
3000 CA Rotterdam
NL
Postbus 2040
3000 CA Rotterdam
NL
Listed location countries
Age
Inclusion criteria
All patients for whom a combination of 2 or more QTc-interval prolonging drugs have been prescribed.
Exclusion criteria
No written informed consent obtained.
Patients in whom life expectancy or clinical situation is such that a risk of heart rhythm disturbances is irrelevant to clinical care.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL14327.078.06 |