Prolonged QT Interval in EKG and Sudden DeathPhase 2NCT01929083

Influence of Progesterone Administration on Drug-Induced QT Interval Lengthening

A Phase 2 study testing Progesterone and Ibutilide in people with Prolonged QT Interval in EKG and Sudden Death, run by Indiana University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 21 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for: Prolonged QT Interval in EKG and Sudden Death
What is being tested?: Progesterone and Ibutilide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 19 participants
Where: 2 sitesUnited States
Study dates: Apr 2013to Jun 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 40 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Female
Age 21-40 years
Premenopausal

Who cannot join

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

Show all 17Show fewer

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Indiana Clinical Research Center
Indianapolis, Indiana, 46202
Purdue University
Indianapolis, Indiana, 46202

Other trials in United States

About this study

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

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.

Conditions: Prolonged QT Interval in EKG and Sudden Death
Being tested: Progesterone, Placebo, Ibutilide
Keywords: Torsades de pointes, Progesterone, Clinical trial, Risk reduction, Electrocardiography
Medical subject headings: Jervell-Lange Nielsen Syndrome, Torsades de Pointes, Risk Reduction Behavior

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01929083
Study group	Role	What they receive
Progesterone	Experimental	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Receives: Drug: Progesterone; Drug: Ibutilide
Placebo	Placebo comparator	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Receives: Drug: Placebo; Drug: Ibutilide

What is being measured

The primary outcome is the main question the study is designed to answer.

Baseline (Pre-Ibutilide) QTcI Intervals
Measured: After 7 days of progesterone or placebo, prior to receiving IV ibutilide
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 = β•RRα, where RR is the interval between adjacent QRS complexes, and α and β are subject-specific correction factors.
Measured: 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours post-ibutilide administration
Maximum % Change From Baseline in QTcI Intervals Following Ibutilide Administration
Measured: After 7 days of progesterone or placebo
Area Under the QTcI - Time Curve (AUEC)
Measured: From beginning of 10-minute ibutilide infusion to 1 hour following ibutilide infusion

Secondary outcomes (1)

Incidence of Progesterone-associated Adverse Effects Compared to Placebo
Measured: During 7 days of treatment with oral progesterone or placebo

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2013Jun 2014

First posted27 Aug 2013 (estimated)
Study startApr 2013
Primary completionJun 2014
Study completionJun 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Prolonged QT Interval in EKG and Sudden DeathStudies of the same condition, open and under way.
More trials run by Indiana UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01929083
Sponsor's protocol ID: 12GRNT12060187
Status last verified: Oct 2015
First submitted: 22 Aug 2013
Last updated: 30 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Study at a glance

From the registry record, last updated by the sponsor on 30 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Influence of Progesterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
ClinicalTrials.gov ID: NCT01929083
Acronym / sponsor ID: 12GRNT12060187
Conditions: Prolonged QT Interval in EKG and Sudden Death
Keywords: Torsades de pointes, Progesterone, Clinical trial, Risk reduction, Electrocardiography
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Indiana UniversityUniversity, hospital or other
Collaborators: American Heart Association
Study start: Apr 2013
Primary completion: Jun 2014 (actual)
Study completion: Jun 2014 (actual)
First posted: 27 Aug 2013 (estimated)
Results: Posted 28 Sep 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Progesterone	Experimental	Drug: Progesterone, Drug: IbutilideSubjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days
Placebo	Placebo comparator	Drug: Placebo, Drug: IbutilideSubjects will receive oral placebo, two capsules once daily every evening for 7 days

Who may qualify

Ages: 21 to 40 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Female
Age 21-40 years
Premenopausal

Key exclusion criteria (17 listed)

Serum potassium ,< 3.6 meq/l
Serum magnesium < 1.8 mg/dl
Serum hemoglobin < 9.0 mg/dl
Serum hematocrit < 26%
Hypertension

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ProgesteroneSubjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Drug	Progesterone
PlaceboSubjects will receive oral placebo two capsules once daily every evening for 7 days	Drug	Placebo
IbutilideIbutilide 0.003 mg/kg administered to all subjects to moderately lengthen the QT interval	Drug	Placebo, Progesterone

Primary outcome

Baseline (Pre-Ibutilide) QTcI Intervals
Time frame: After 7 days of progesterone or placebo, prior to receiving IV ibutilide
Maximum Individual-corrected QT Interval (QTcI)
Time frame: 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours post-ibutilide administration
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 = β•RRα, where RR is the interval between adjacent QRS complexes, and α and β are subject-specific correction factors.
Maximum % Change From Baseline in QTcI Intervals Following Ibutilide Administration
Time frame: After 7 days of progesterone or placebo
Area Under the QTcI - Time Curve (AUEC)
Time frame: From beginning of 10-minute ibutilide infusion to 1 hour following ibutilide infusion

1 secondary outcome

Incidence of Progesterone-associated Adverse Effects Compared to Placebo
Time frame: During 7 days of treatment with oral progesterone or placebo

Results and safety

Results posted to the registry on 28 Sep 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Progesterone First, Then Placebo	10	7
Placebo First, Then Progesterone	9	9

Primary outcome: Baseline (Pre-Ibutilide) QTcI Intervals

Time frame: After 7 days of progesterone or placebo, prior to receiving IV ibutilide. Mean (Standard Deviation). Unit: ms

Measure	Progesterone n = 15	Placebo n = 15
Value	412 (15)	419 (14)

Progesterone vs Placebo: p = 0.04, t-test, 2 sided

Primary outcome: Maximum Individual-corrected QT Interval (QTcI)

Time frame: 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours post-ibutilide administration. Mean (Standard Deviation). Unit: ms

Measure	Progesterone n = 15	Placebo n = 15
Value	443 (17)	458 (19)

Progesterone vs Placebo: p = 0.003, t-test, 2 sided

Primary outcome: Maximum % Change From Baseline in QTcI Intervals Following Ibutilide Administration

Time frame: After 7 days of progesterone or placebo. Mean (Standard Deviation). Unit: percentage change from baseline value

Measure	Progesterone n = 15	Placebo n = 15
Value	7.5 (2.4)	9.3 (3.4)

Progesterone vs Placebo: p = 0.02, t-test, 2 sided

Primary outcome: Area Under the QTcI - Time Curve (AUEC)

Time frame: From beginning of 10-minute ibutilide infusion to 1 hour following ibutilide infusion. Mean (Standard Deviation). Unit: ms*hr

Measure	Progesterone n = 15	Placebo n = 15
Value	497 (13)	510 (16)

Progesterone vs Placebo: p = 0.002, t-test, 2 sided

1 secondary outcome is reported in the full results.

Adverse events

Time frame: During 7 days of therapy with progesterone or placebo. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Progesterone	1 of 16 (6.3%)	9 of 16 (56.3%)	Not reported
Placebo	0 of 17 (0%)	2 of 17 (11.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James E Tisdale, BSc, PharmD principal investigator

Purdue University & Indiana University

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Progesterone and Ibutilide in people with Prolonged QT Interval in EKG and Sudden Death, run by Indiana University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Baseline (Pre-Ibutilide) QTcI Intervals (time frame: After 7 days of progesterone or placebo, prior to receiving IV ibutilide). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01929083.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2015; AzTrials last refreshed its copy on 7 Nov 2026.