CompletedPhase 4

Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening

United States73 participantsStarted 2021-09-02

Plain-language summary

This research will determine if: 1) Oral progesterone attenuates drug-induced QT interval, J-Tpeak and Tpeak-Tend lengthening in postmenopausal women 50 years of age or older, and 2) Transdermal testosterone attenuates drug-induced QT interval, J-Tpeak and Tpeak-Tend lengthening in men 65 years of age or older. This investigation will consist of two concurrent prospective, randomized, double-blind, placebo-controlled crossover-design studies in a) Postmenopausal women, and b) Men 65 years of age or older. Study 1: Each postmenopausal woman will take progesterone or placebo capsules for 1 week. After a 14-day "washout" (no progesterone or placebo) each subject will then take the alternative therapy (progesterone or placebo) for 1 week. After 7 days of each treatment, subjects will present to the clinical research center to receive a small dose of the QT interval-lengthening drug ibutilide, and the effect on the QT, J-Tpeak and Tpeak-Tend intervals during the progesterone and placebo phases will be compared. Study 2: Each man 65 years of age or older will apply transdermal testosterone or transdermal placebo gel for 3 days. After a 7-day "washout" (no testosterone or placebo) each subject will then apply the alternative therapy (testosterone or placebo gel) for 1 week. After 3 days of each treatment, subjects will present to the clinical research center to receive a small dose of the QT interval-lengthening drug ibutilide, and the effect on the QT, J-Tpeak and Tpeak-Tend intervals during the testosterone and placebo phases will be compared.

Who can participate

Age range50 Years – 99 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: Postmenopausal Women: * Age 50-99 years old * Postmenopausal (have not has a menstrual period for 12 months or longer) Exclusion Criteria: Postmenopausal women: * Subject reported history of breast, uterine and ovarian cervical cancer * Subject reported history of hysterectomy and/or ovariectomy * Subject reported taking any hormone replacement therapy (prescription, nonprescription or herbal supplement) * Weight \< 60 kg at time of screening visit * Weight \>135 kg at time of screening visit * Serum K+ \<3.6 mEq/L at time of any ibutilide dosing visit * Serum Mg2+ \<1.8 mg/dL at time of screening visit * Hematocrit \<26% * AST or ALT \> 3x the upper limit of normal (determined by testing lab ranges) at the time of screening visit * Baseline Bazett's-corrected QTc \>450 ms (during any visit prior to ibutilide dosing) * Baseline QRS \> 120 ms (at time of baseline visit) * Diagnosis of heart failure due to reduced or preserved ejection fraction * Subject reported family history of long QT syndrome, TdP, or sudden cardiac death not associated with acute myocardial infarction * Self-reported personal history of long QT syndrome, sudden cardiac death not associated with acute myocardial infarction * Subject reported history any prolonged arrhythmia for which treatment was required * Subject reported history of a myocardial infarction * Subject reported history of coronary artery disease * Sustained arrythmia found at baseline screening prior to any study v…

What they're measuring

Pre-ibutilide QT-F and QT-Fram intervals

Timeframe: Morning of day 8 (after 7 days of progesterone/placebo)

Pre-ibutilide QT-F and QT-Fram intervals

Timeframe: Morning of day 4 (after 3 days of testosterone/placebo)

Maximum post-ibutilide QT-F and QT-Fram intervals

Timeframe: From initiation of ibutilide infusion and for 8 hours after the end of ibutilide infusion

Percent change from baseline (pre-ibutilide) in maximum QT-F and QT-Fram intervals

Timeframe: From initiation of ibutilide infusion and for 8 hours after the end of ibutilide infusion

Area under the QT-F and QT-Fram versus time curves during and for 1 hour following ibutilide infusion

Timeframe: From initiation of ibutilide infusion and for 1 hour after the end of ibutilide infusion

Area under the QT-F and QT-Fram versus time curves during and for 8 hours following ibutilide infusion

Timeframe: From initiation of ibutilide infusion and for 8 hours after the end of ibutilide infusion

Pre-ibutilide heart rate-corrected J-Tpeak (J-Tpeakc) intervals

Timeframe: Morning of day 8 (after 7 days of progesterone/placebo)

Trial details

NCT IDNCT04675788

SponsorIndiana University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-04-16

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