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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01929083
Other study ID # 12GRNT12060187
Secondary ID
Status Completed
Phase Phase 2
First received August 22, 2013
Last updated October 29, 2015
Start date April 2013
Est. completion date June 2014

Study information

Verified date October 2015
Source Indiana University
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

Female sex is an independent risk factor for the potentially fatal drug-induced arrhythmia (irregular heartbeat) known as torsades de pointes (TdP), which is associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram (ECG). Mechanisms for this increased risk in women are not well-understood. QTc interval duration has been shown to fluctuate throughout the phases of the menstrual cycle. Evidence indicates that the QTc interval response to drugs that may cause TdP is greater during the menses and ovulation phases of the menstrual cycle, during which serum progesterone concentrations are lowest, and lesser during the luteal phase, during which serum progesterone concentrations are highest. Additional evidence from our laboratory suggests that progesterone may be protective against TdP. Specific Aim 1: Establish the influence of oral progesterone administration as a preventive method by which to diminish the degree of drug-induced QT interval prolongation in women. Working hypothesis: Oral progesterone administration effectively attenuates enhanced drug-induced QT interval response in women. To test this hypothesis, progesterone or placebo will be administered in a crossover fashion to women during the menses phase of the menstrual cycle. QTc interval response to low-dose ibutilide, a drug known to lengthen the QT interval, will be assessed. The primary endpoint will be individually-corrected QT interval (QTcI) response to ibutilide, in the presence and absence of progesterone, which will be assessed by: 1) Effect on maximum change in QTcI, and 2) Area under the QTcI interval-time curves (AUEC). At the conclusion of this study, we will have established that oral progesterone administration is a safe and effective method of attenuating drug-induced QT interval prolongation.


Recruitment information / eligibility

Status Completed
Enrollment 19
Est. completion date June 2014
Est. primary completion date June 2014
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 21 Years to 40 Years
Eligibility Inclusion Criteria:

- Female

- Age 21-40 years

- Premenopausal

Exclusion Criteria:

Serum potassium ,< 3.6 meq/l

- Serum magnesium < 1.8 mg/dl

- Serum hemoglobin < 9.0 mg/dl

- Serum hematocrit < 26%

- Hypertension

- Coronary artery disease

- Heart failure

- Liver disease

- Kidney disease

- Serum creatinine > 1.5 mg/dl

- Taking hormone contraceptives

- Baseline Bazett's correct QTc interval > 450 ms

- Family history of long-QT syndrome, arrhythmias, sudden cardiac death

- Concomitant use of any QT prolonging drug

- Pregnancy

- weight < 45 kg

- Unwillingness to use non-hormonal forms of birth control during the study period

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention


Related Conditions & MeSH terms


Intervention

Drug:
Progesterone
Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days
Placebo
Subjects will receive oral placebo two capsules once daily every evening for 7 days
Ibutilide
Ibutilide 0.003 mg/kg administered to all subjects to moderately lengthen the QT interval

Locations

Country Name City State
United States Indiana Clinical Research Center Indianapolis Indiana
United States Purdue University Indianapolis Indiana

Sponsors (2)

Lead Sponsor Collaborator
Indiana University American Heart Association

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Adverse Effects Associated With Ibutilide in the Progesterone and Placebo Phases Within 8 hours following ibutilide administration Yes
Other Maximum (Peak) Serum Ibutilide Concentrations During Progesterone and Placebo Phases Within 1 hour following ibutilide administration (0, 15 & 30 minutes and 1 hours.) No
Other Serum Estradiol Concentrations During the Progesterone and Placebo Phases Following 7 days of progesterone or placebo No
Other Serum Progesterone Concentrations During Progesterone and Placebo Phases After 7 days of progesterone or placebo No
Other Ratio of Serum Progesterone:Estradiol Concentrations During the Progesterone and Placebo Phases After 7 days of progesterone or placebo No
Primary Baseline (Pre-Ibutilide) QTcI Intervals After 7 days of progesterone or placebo, prior to receiving IV ibutilide No
Primary Maximum Individual-corrected QT Interval (QTcI) QT intervals will be corrected as follows: Prior to randomization, subjects will come to the Indiana Clinical Research Center for a 12-hour stay, during which three ECGs, one minute apart, will be obtained at the following times: 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours. Subjects will be discharged, and then return then next morning for the 24 hour ECG. QT and RR intervals will be used to determine each subject's individual rate-corrected QT interval (QTcI) using the parabolic model QT = ß•RRa, where RR is the interval between adjacent QRS complexes, and a and ß are subject-specific correction factors. 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours post-ibutilide administration No
Primary Maximum % Change From Baseline in QTcI Intervals Following Ibutilide Administration After 7 days of progesterone or placebo No
Primary Area Under the QTcI - Time Curve (AUEC) From beginning of 10-minute ibutilide infusion to 1 hour following ibutilide infusion No
Secondary Incidence of Progesterone-associated Adverse Effects Compared to Placebo During 7 days of treatment with oral progesterone or placebo Yes