Reducing the Risk of Drug-Induced QT Interval Lengthening in Women

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: Female

Summary

This research will determine if oral progesterone attenuates drug-induced QT interval lengthening in a) Postmenopausal women 50 years of age or older, and b) Premenopausal women studied during the ovulation phase of the menstrual cycle. This investigation will consist of two concurrent prospective, randomized, double-blind, placebo-controlled crossover-design studies in a) Postmenopausal women, and b) Premenopausal women. Each subject will take progesterone or placebo capsules for 1 week. After a two-week "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

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Indiana University
• Collaborators: American Heart Association; Purdue University
• Treatments: Ibutilide; Progesterone

Criteria

Inclusion Criteria:

Postmenopausal women:

• 50 years of age or older

• No menstrual periods for 365 days or longer

Premenopausal women:

• 21-40 years of age

Exclusion Criteria:

• History of breast, uterine or ovarian cancer

• History of hysterectomy and/or ovariectomy

• Weight > 135 kg

• Serum K+ < 3.6 mEq/L;

• Serum Mg2+ < 1.8 mg/dL;

• Hematocrit < 26%;

• Hepatic transaminases > 3x upper limit of normal;

• Baseline Bazett's-corrected QT interval > 450 ms

• Taking hormone replacement therapy

• Diagnosis of heart failure

• Symptoms associated with heart failure:

• Pitting edema > 2+

• Crackles or rales on lung auscultation

• S3 or S4 heart sounds

• Unable to climb at least 2 flights of stairs without becoming short of breath

• Current ECG rhythm of atrial fibrillation or other tachyarrhythmia

• Family or personal history of long-QT syndrome or sudden cardiac death not associated with acute myocardial infarction

• Concomitant use of any QTc interval-prolonging drug.

• Permanently paced ventricular rhythm

• Pregnancy

• Using any hormonal contraceptives [oral contraceptives, hormone-secreting intrauterine devices (IUDs), hormonal implants]