DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Influence of Progesterone Administration on Drug-Induced QT Interval Lengthening

Information source: Indiana University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Prolonged QT Interval in EKG and Sudden Death

Intervention: Progesterone (Drug); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Indiana University

Official(s) and/or principal investigator(s):
James E Tisdale, BSc, PharmD, Principal Investigator, Affiliation: Purdue University & Indiana University

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.

Clinical Details

Official title: Influence of Progesterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes

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

Primary outcome:

Maximum individual-corrected QT interval (QTcI)

Area under the QTcI - time curve (AUEC)

QTcI EC50

Secondary outcome: Incidence of progesterone-associated adverse effects

Eligibility

Minimum age: 21 Years. Maximum age: 40 Years. Gender(s): Female.

Criteria:

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

Locations and Contacts

Indiana Clinical Research Center, Indianapolis, Indiana 46202, United States

Purdue University, Indianapolis, Indiana 46202, United States

Additional Information

Starting date: April 2013
Last updated: March 12, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017