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Randomized Controlled Trial
. 2005 Oct;10(4 Suppl):59-66.
doi: 10.1111/j.1542-474X.2005.00077.x.

Safety and efficacy of flecainide in subjects with Long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial

Arthur J Moss  1 , John R Windle, W Jackson Hall, Wojciech Zareba, Jennifer L Robinson, Scott McNitt, Patricia Severski, Spencer Rosero, James P Daubert, Ming Qi, Michael Cieciorka, Allan S Manalan
Affiliations
Randomized Controlled Trial

Safety and efficacy of flecainide in subjects with Long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial

Arthur J Moss et al. Ann Noninvasive Electrocardiol. 2005 Oct.

Abstract

Background: We conducted a study of chronic therapy with flecainide versus placebo in a small group of LQT-3 patients with the DeltaKPQ deletion to evaluate the safety and efficacy of flecainide in this genetic disorder. In vitro studies have shown that flecainide provides correction of the impaired inactivation associated with the DeltaKPQ deletion.

Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted with flecainide and placebo in six male LQT-3 subjects with the DeltaKPQ deletion.

Results: The lowest possible dose of flecainide associated with at least a 40 ms reduction in the QTc interval was determined in an initial open-label, dose-ranging investigation using one-fourth or half of the recommended maximal antiarrhythmic flecainide dose. QTc reduction was achieved with a flecainide dose of 1.5 mg/kg per day in 4 subjects and with 3.0 mg/kg per day in 2 subjects. Subjects were randomized to four 6-month alternating periods of flecainide and placebo therapy based on the open-label dose findings. Average QTc values during placebo and flecainide therapies were 534 ms and 503 ms, respectively, with an adjusted reduction in QTc of -27.1 ms (95% confidence interval: -36.8 ms to -17.4 ms; P<0.001) at a mean flecainide blood level of 0.11+/-0.05 microg/ml. Minimal prolongation in QRS occurred (mean: +2.5 ms), and there were no major adverse cardiac effects.

Conclusions: Chronic low-dose flecainide significantly shortens the QTc interval in LQT-3 subjects with the DeltaKPQ mutation. No major adverse drug effects were observed with flecainide during this trial, but the sample size is not large enough to evaluate the safety of flecainide therapy in patients with this mutation.

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Figures

Figure 1
Figure 1
QTc versus flecainide blood levels during the randomized placebo or flecainide therapy. The linear regression equation relating these two parameters (126 observations) is QTc = 0.53–0.28(flecainide concentration), with R2= 0.16.
Figure 2
Figure 2
QTc in seconds at multiple times during each of four 6‐month periods of randomized therapy with placebo (striped bars; average QTc = 0.52s) or flecainide (gray bars; average QTc = 0.49s) in one LQT‐3 subject.
Figure 3
Figure 3
Electrocardiographic tracings during selected phases of placebo and flecainide therapy in the same LQT‐3 subject as presented in Figure 2.
See this image and copyright information in PMC

References

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