Long QT SyndromePhase 4NCT02513940
Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
A Phase 4 study testing Testosterone, Progesterone and Ibutilide in people with Long QT Syndrome, run by Indiana University at 1 site in United States.
Trial summary
Torsades de pointes (TdP) is a potentially fatal ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. More than 50 commonly used drugs available on the US market may cause QTc interval prolongation and TdP. Read more about this study
- Who is it for?
- Ages 65 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Long QT Syndrome
- What is being tested?
- Testosterone, 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
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to 19 Oct 2017
- Phase
- Phase 4
- 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 65 years and older
- Men only
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Men ≥ 65 years of age
Who cannot join
- Prostate cancer; history of prostate cancer;
- History of breast cancer; benign prostatic hypertrophy;
- Weight < 60 kg
- Weight > 135 kg
- Serum k+ < 3.6 mEq/L;
- Serum mg2+ < 1.8 mg/dL;
Show all 13Show fewer
- Hemoglobin < 9.0 mg/dL;
- Hematocrit < 26%;
- Hepatic transaminases > 3x upper limit of normal;
- Baseline Bazett's-corrected QT interval > 450 ms
- Heart failure due to reduced ejection fraction (left ventricular ejection fraction < 40%)
- Family or personal history of long-QT syndrome, arrhythmias or sudden cardiac death;
- Concomitant use of any QT interval-prolonging drug.
Trial locations and contacts
1 site in 1 country.
About this study
Torsades de pointes (TdP) is a potentially fatal ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. More than 50 commonly used drugs available on the US market may cause QTc interval prolongation and TdP. While TdP occurs more commonly in women, 33-45% of all cases of TdP have occurred in men. Older age is a risk factor for drug-induced TdP in men, possibly due to declining serum testosterone concentrations. Available evidence shows an inverse relationship between QTc intervals and serum testosterone concentrations. In addition, experimental data, including those from the investigators' laboratory, suggest that both exogenous testosterone or progesterone administration may be protective against prolongation of ventricular repolarization and TdP. Specific Aim: Establish the influence of transdermal testosterone administration and oral progesterone administration as preventive methods by which to diminish the degree of drug-induced QT interval prolongation in men 65 years of age or older. Hypothesis: Transdermal testosterone administration and oral progesterone administration both effectively attenuate drug-induced QT interval response in older men. To test this hypothesis, transdermal testosterone, oral progesterone or placebo will be administered in a 3-way crossover study to men 65 years of age or older. QTc interval response to low-dose ibutilide will be assessed. The primary endpoints will be Fridericia-corrected QT interval (QTF) response to ibutilide, in the presence and absence of testosterone, and in the presence or absence of progesterone: 1) Effect on pre-ibutilide QTF, 2) Effect on maximum post-ibutilide QTF, 3) Effect on % change in post-ibutilide QTF, and 2) Area under the QTF interval-time curves.
- Conditions
- Long QT Syndrome
- Being tested
- Testosterone, Progesterone, Placebo, Ibutilide
- Keywords
- Torsades de pointes, Testosterone, Progesterone, Clinical trial, Risk reduction, Electrocardiography
- Medical subject headings
- Long QT 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.
TestosteroneDrug
Also called Androgel
Subjects will receive transdermal testosterone gel 1% 100 mg daily for 7 days
ProgesteroneDrug
Also called Generic
Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days
PlaceboDrug
Also called Lactose
Subjects will receive placebo transdermal gel and placebo (lactose) capsules
IbutilideDrug
Also called Corvert
Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval
| Study group | Role | What they receive |
|---|---|---|
| Testosterone - progesterone - placebo | Experimental | Subjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days Receives: Drug: Testosterone; Drug: Progesterone; Drug: Placebo; Drug: Ibutilide |
| Testosterone - placebo - progesterone | Experimental | Subjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo ( 2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. Receives: Drug: Testosterone; Drug: Progesterone; Drug: Placebo; Drug: Ibutilide |
| Progesterone - testosterone - placebo | Experimental | Subjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days Receives: Drug: Testosterone; Drug: Progesterone; Drug: Placebo; Drug: Ibutilide |
| Progesterone - placebo - testosterone | Experimental | Subjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. Receives: Drug: Testosterone; Drug: Progesterone; Drug: Placebo; Drug: Ibutilide |
| Placebo - testosterone - progesterone | Experimental | Subjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. Receives: Drug: Testosterone; Drug: Progesterone; Drug: Placebo; Drug: Ibutilide |
| Placebo - progesterone - testosterone | Experimental | Subjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. Receives: Drug: Testosterone; Drug: Progesterone; Drug: Placebo; Drug: Ibutilide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline (Pre-ibutilide) Individualized Rate-corrected QT Interval (QTF)
QT interval is an electrocardiogram (ECG) measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers (EP Calipers 1.6). QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. Only clearly discernable QT intervals were measured. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. The baseline QTF assesses the influence of testosterone and progesterone on naturally-occurring (before ibutilide administration) QTF
Measured: Following 7 days of testosterone, progesterone or placebo
Maximum QTF Following Ibutilide 0.003 mg/kg
QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. Maximum QTF is the longest QTF measured following ibutilide at any time point.
Measured: Within 8 hours following ibutilide administration
Maximum Percent Change From Pretreatment Value in QTF Following Ibutilide 0.003 mg/kg
QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals were corrected using the Fridericia (QTF) method.
Measured: Within 8 hours of ibutilide administration
Secondary outcomes (2)
Area Under the QTF Versus Time Curve for 0-1 Hour Following Ibutilide 0.003 mg/kg
Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. Area under the QTF curve was calculated using the trapezoidal rule and reflects overall QTF interval "exposure" over time.
Measured: 1 hour following ibutilide administration
Number of Participants With Adverse Effects Associated With Testosterone, Progesterone and Placebo
Adverse effects were assessed by study investigators using telephone calls during the 7-day treatment period in each phase, as well as by asking participants about adverse effects on ibutilide administration days
Measured: During 7 day administration periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2015 (estimated)
- Study startMay 2016
- Primary completion19 Oct 2017
- Study completion19 Oct 2017
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Long QT SyndromeStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association, Purdue University
- Responsible party
- Principal investigator, James E. Tisdale, Indiana University
- Investigators
- James E Tisdale, PharmD, Principal investigator, Purdue University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02513940
- Sponsor's protocol ID
- 1507526854
- Status last verified
- Aug 2019
- First submitted
- 29 Jul 2015
- Last updated
- 28 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Muensterman ET, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, Tisdale JE. Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men: A Randomized, Double-Blind, Placebo-Controlled Crossover-Design Study. Circulation. 2019 Sep 24;140(13):1127-1129. doi: 10.1161/CIRCULATIONAHA.119.041395. Epub 2019 Sep 23. No abstract available.
PubMed 31545681Tomaselli Muensterman E, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, Tisdale JE. Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both Early and Late Ventricular Repolarization in Older Men. Clin Pharmacol Ther. 2021 Jun;109(6):1499-1504. doi: 10.1002/cpt.2072. Epub 2020 Nov 15.
PubMed 33020898
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
- ClinicalTrials.gov ID
- NCT02513940
- Acronym / sponsor ID
- 1507526854
- Conditions
- Long QT Syndrome
- Keywords
- Torsades de pointes, Testosterone, Progesterone, Clinical trial, Risk reduction, Electrocardiography
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- American Heart Association, Purdue University
- Study start
- May 2016 (actual)
- Primary completion
- 19 Oct 2017 (actual)
- Study completion
- 19 Oct 2017 (actual)
- First posted
- 3 Aug 2015 (estimated)
- Results
- Posted 6 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Torsades de pointes (TdP) is a potentially fatal ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. More than 50 commonly used drugs available on the US market may cause QTc interval prolongation and TdP. While TdP occurs more commonly in women, 33-45% of all cases of TdP have occurred in men. Older age is a risk factor for drug-induced TdP in men, possibly due to declining serum testosterone concentrations. Available evidence shows an inverse relationship between QTc intervals and serum testosterone concentrations. In addition, experimental data, including those from the investigators' laboratory, suggest that both exogenous testosterone or progesterone administration may be protective against prolongation of ventricular repolarization and TdP. Specific Aim: Establish the influence of transdermal testosterone administration and oral progesterone administration as preventive methods by which to diminish the degree of drug-induced QT interval prolongation in men 65 years of age or older. Hypothesis: Transdermal testosterone administration and oral progesterone administration both effectively attenuate drug-induced QT interval response in older men. To test this hypothesis, transdermal testosterone, oral progesterone or placebo will be administered in a 3-way crossover study to men 65 years of age or older. QTc interval response to low-dose ibutilide will be assessed. The primary endpoints will be Fridericia-corrected QT interval (QTF) response to ibutilide, in the presence and absence of testosterone, and in the presence or absence of progesterone: 1) Effect on pre-ibutilide QTF, 2) Effect on maximum post-ibutilide QTF, 3) Effect on % change in post-ibutilide QTF, and 2) Area under the QTF interval-time curves.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Testosterone - progesterone - placebo | Experimental | Drug: Testosterone, Drug: Progesterone, Drug: Placebo, Drug: IbutilideSubjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days |
| Testosterone - placebo - progesterone | Experimental | Drug: Testosterone, Drug: Progesterone, Drug: Placebo, Drug: IbutilideSubjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo ( 2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. |
| Progesterone - testosterone - placebo | Experimental | Drug: Testosterone, Drug: Progesterone, Drug: Placebo, Drug: IbutilideSubjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days |
| Progesterone - placebo - testosterone | Experimental | Drug: Testosterone, Drug: Progesterone, Drug: Placebo, Drug: IbutilideSubjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. |
| Placebo - testosterone - progesterone | Experimental | Drug: Testosterone, Drug: Progesterone, Drug: Placebo, Drug: IbutilideSubjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. |
| Placebo - progesterone - testosterone | Experimental | Drug: Testosterone, Drug: Progesterone, Drug: Placebo, Drug: IbutilideSubjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. |
Who may qualify
- Ages
- 65 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- Men ≥ 65 years of age
Key exclusion criteria (13 listed)
- Prostate cancer; history of prostate cancer;
- History of breast cancer; benign prostatic hypertrophy;
- Weight < 60 kg
- Weight > 135 kg
- Serum k+ < 3.6 mEq/L;
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 |
|---|---|---|
| TestosteroneAlso: AndrogelSubjects will receive transdermal testosterone gel 1% 100 mg daily for 7 days | Drug | Placebo - progesterone - testosterone, Placebo - testosterone - progesterone, Progesterone - placebo - testosterone, Progesterone - testosterone - placebo, Testosterone - placebo - progesterone, Testosterone - progesterone - placebo |
| ProgesteroneAlso: GenericSubjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days | Drug | Placebo - progesterone - testosterone, Placebo - testosterone - progesterone, Progesterone - placebo - testosterone, Progesterone - testosterone - placebo, Testosterone - placebo - progesterone, Testosterone - progesterone - placebo |
| PlaceboAlso: LactoseSubjects will receive placebo transdermal gel and placebo (lactose) capsules | Drug | Placebo - progesterone - testosterone, Placebo - testosterone - progesterone, Progesterone - placebo - testosterone, Progesterone - testosterone - placebo, Testosterone - placebo - progesterone, Testosterone - progesterone - placebo |
| IbutilideAlso: CorvertIbutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval | Drug | Placebo - progesterone - testosterone, Placebo - testosterone - progesterone, Progesterone - placebo - testosterone, Progesterone - testosterone - placebo, Testosterone - placebo - progesterone, Testosterone - progesterone - placebo |
Primary outcome
Baseline (Pre-ibutilide) Individualized Rate-corrected QT Interval (QTF)
Time frame: Following 7 days of testosterone, progesterone or placebo
QT interval is an electrocardiogram (ECG) measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers (EP Calipers 1.6). QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. Only clearly discernable QT intervals were measured. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. The baseline QTF assesses the influence of testosterone and progesterone on naturally-occurring (before ibutilide administration) QTF
Maximum QTF Following Ibutilide 0.003 mg/kg
Time frame: Within 8 hours following ibutilide administration
QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. Maximum QTF is the longest QTF measured following ibutilide at any time point.
Maximum Percent Change From Pretreatment Value in QTF Following Ibutilide 0.003 mg/kg
Time frame: Within 8 hours of ibutilide administration
QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals were corrected using the Fridericia (QTF) method.
2 secondary outcomes
Area Under the QTF Versus Time Curve for 0-1 Hour Following Ibutilide 0.003 mg/kg
Time frame: 1 hour following ibutilide administration
Number of Participants With Adverse Effects Associated With Testosterone, Progesterone and Placebo
Time frame: During 7 day administration periods
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31545681Muensterman ET, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, Tisdale JE. Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men: A Randomized, Double-Blind, Placebo-Controlled Crossover-Design Study. Circulation. 2019 Sep 24;140(13):1127-1129. doi: 10.1161/CIRCULATIONAHA.119.041395. Epub 2019 Sep 23. No abstract available.
- Derived from this study: PubMed 33020898Tomaselli Muensterman E, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, Tisdale JE. Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both Early and Late Ventricular Repolarization in Older Men. Clin Pharmacol Ther. 2021 Jun;109(6):1499-1504. doi: 10.1002/cpt.2072. Epub 2020 Nov 15.
- Individual participant dataSharing planned: Undecided
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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, PharmD principal investigator
Purdue University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Testosterone, Progesterone and Ibutilide in people with Long QT Syndrome, run by Indiana University at 1 site 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 1 inclusion and 13 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 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 6 Mar 2019). 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) Individualized Rate-corrected QT Interval (QTF) (time frame: Following 7 days of testosterone, progesterone or placebo). The study lists 3 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 NCT02513940, which also lists 2 linked publications.
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 28 Aug 2019.