Influence of Progesterone Administration on Drug-Induced QT Interval Lengthening
Status:
Completed
Trial end date:
2014-06-01
Target enrollment:
Participant gender:
Summary
Female sex is an independent risk factor for the potentially fatal drug-induced arrhythmia
(irregular heartbeat) known as torsades de pointes (TdP), which is associated with
prolongation of the corrected QT (QTc) interval on the electrocardiogram (ECG). Mechanisms
for this increased risk in women are not well-understood. QTc interval duration has been
shown to fluctuate throughout the phases of the menstrual cycle. Evidence indicates that the
QTc interval response to drugs that may cause TdP is greater during the menses and ovulation
phases of the menstrual cycle, during which serum progesterone concentrations are lowest, and
lesser during the luteal phase, during which serum progesterone concentrations are highest.
Additional evidence from our laboratory suggests that progesterone may be protective against
TdP. Specific Aim 1: Establish the influence of oral progesterone administration as a
preventive method by which to diminish the degree of drug-induced QT interval prolongation in
women. Working hypothesis: Oral progesterone administration effectively attenuates enhanced
drug-induced QT interval response in women. To test this hypothesis, progesterone or placebo
will be administered in a crossover fashion to women during the menses phase of the menstrual
cycle. QTc interval response to low-dose ibutilide, a drug known to lengthen the QT interval,
will be assessed. The primary endpoint will be individually-corrected QT interval (QTcI)
response to ibutilide, in the presence and absence of progesterone, which will be assessed
by: 1) Effect on maximum change in QTcI, and 2) Area under the QTcI interval-time curves
(AUEC). At the conclusion of this study, we will have established that oral progesterone
administration is a safe and effective method of attenuating drug-induced QT interval
prolongation.