Safety and efficacy of flecainide in subjects with long QT-3 syndrome (ΔKPQ mutation)

A randomized, double-blind, placebo-controlled clinical trial

Arthur J. Moss, John Robert 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

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Background: We conducted a study of chronic therapy with flecainide versus placebo in a small group of LQT-3 patients with the ΔKPQ 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 ΔKPQ deletion. Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted with flecainide and placebo in six male LQT-3 subjects with the ΔKPQ 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 μg/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 ΔKPQ 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.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalAnnals of Noninvasive Electrocardiology
Volume10
Issue numberSUPPL. 4
DOIs
StatePublished - Oct 1 2005

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Flecainide
Controlled Clinical Trials
Placebos
Safety
Mutation
Long QT syndrome type 3
Inborn Genetic Diseases
Therapeutics
Sample Size

Keywords

  • Antiarrhythmic agents
  • Ion channels
  • Long-QT syndrome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Safety and efficacy of flecainide in subjects with long QT-3 syndrome (ΔKPQ mutation) : A randomized, double-blind, placebo-controlled clinical trial. / Moss, Arthur J.; Windle, John Robert; Hall, W. Jackson; Zareba, Wojciech; Robinson, Jennifer L.; McNitt, Scott; Severski, Patricia; Rosero, Spencer; Daubert, James P.; Qi, Ming; Cieciorka, Michael; Manalan, Allan S.

In: Annals of Noninvasive Electrocardiology, Vol. 10, No. SUPPL. 4, 01.10.2005, p. 59-66.

Research output: Contribution to journalArticle

Moss, AJ, Windle, JR, Hall, WJ, Zareba, W, Robinson, JL, McNitt, S, Severski, P, Rosero, S, Daubert, JP, Qi, M, Cieciorka, M & Manalan, AS 2005, 'Safety and efficacy of flecainide in subjects with long QT-3 syndrome (ΔKPQ mutation): A randomized, double-blind, placebo-controlled clinical trial', Annals of Noninvasive Electrocardiology, vol. 10, no. SUPPL. 4, pp. 59-66. https://doi.org/10.1111/j.1542-474X.2005.00077.x
Moss, Arthur J. ; Windle, John Robert ; Hall, W. Jackson ; Zareba, Wojciech ; Robinson, Jennifer L. ; McNitt, Scott ; Severski, Patricia ; Rosero, Spencer ; Daubert, James P. ; Qi, Ming ; Cieciorka, Michael ; Manalan, Allan S. / Safety and efficacy of flecainide in subjects with long QT-3 syndrome (ΔKPQ mutation) : A randomized, double-blind, placebo-controlled clinical trial. In: Annals of Noninvasive Electrocardiology. 2005 ; Vol. 10, No. SUPPL. 4. pp. 59-66.
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abstract = "Background: We conducted a study of chronic therapy with flecainide versus placebo in a small group of LQT-3 patients with the ΔKPQ 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 ΔKPQ deletion. Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted with flecainide and placebo in six male LQT-3 subjects with the ΔKPQ 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 μg/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 ΔKPQ 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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T2 - A randomized, double-blind, placebo-controlled clinical trial

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AU - Windle, John Robert

AU - Hall, W. Jackson

AU - Zareba, Wojciech

AU - Robinson, Jennifer L.

AU - McNitt, Scott

AU - Severski, Patricia

AU - Rosero, Spencer

AU - Daubert, James P.

AU - Qi, Ming

AU - Cieciorka, Michael

AU - Manalan, Allan S.

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