Phase 4 N=27 Randomized Quadruple-blind Prevention

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

Long QT Syndrome · Abnormalities, Drug-Induced

Bottom Line

View on ClinicalTrials.gov: NCT03834883 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jul 2025

Primary outcome: Primary: Baseline (Pre-ibutilide) QT-F Intervals — 417; 421; 413; 414 ms — p=0.07

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Progesterone (Drug); Ibutilide (Drug)
Age: Adult, Older Adult · 21+ yrs
Sex: Female
Sponsor: Indiana University
Primary completion: May 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Baseline (Pre-ibutilide) QT-F Intervals	417; 421; 413; 414	0.07
PRIMARY Maximum Post-ibutilide QT-F Intervals	465; 475; 450; 460	0.006 sig
PRIMARY % Change From Baseline (Pre-ibutilide) in Maximum QT-F Intervals	11.3; 12.4; 9.2; 11.0	0.16
PRIMARY Area Under the QT-F Versus Time Curves During and for 1 Hour Following Ibutilide Infusion	500; 510; 480; 510	0.002 sig
SECONDARY Baseline (Pre-ibutilide) Heart Rate-corrected J-Tpeak (J-Tpeakc) Intervals	218; 221; 219; 219	0.20
SECONDARY Maximum Post-ibutilide J-Tpeakc Intervals	230; 272; 234; 243	0.01 sig
SECONDARY % Change From Baseline (Pre-ibutilide) in Maximum J-Tpeakc Intervals	11.7; 14.1; 6.1; 7.9	—
SECONDARY Area Under the J-Tpeakc Versus Time Curve During and for 1 Hour Following Ibutilide Infusion	248; 276; 258; 261	0.015 sig
SECONDARY Baseline (Pre-ibutilide) Tpeak-Tend Intervals	85; 88; 79; 80	0.0005 sig
SECONDARY Maximum Post-ibutilide Tpeak-Tend Intervals	99; 102; 81; 87	0.017 sig
SECONDARY % Change From Baseline (Pre-ibutilide) Maximum Tpeak-Tend Intervals	16.1; 16.0; 8.8; 10.5	0.83
SECONDARY Area Under the Tpeak-Tend Versus Time Curves During and for 1 Hour Following Ibutilide Infusion	98; 104; 90; 97	<0.0001 sig

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

Eligibility 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+ 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]

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Data sourced from ClinicalTrials.gov (NCT03834883). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.