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Trial record 51 of 74 for:    "Andersen-Tawil syndrome" OR "Long QT Syndrome"

Influence of Progesterone Administration on Drug-Induced QT Interval Lengthening

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ClinicalTrials.gov Identifier: NCT01929083
Recruitment Status : Completed
First Posted : August 27, 2013
Results First Posted : September 28, 2015
Last Update Posted : October 30, 2015
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
James E. Tisdale, Purdue University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Prolonged QT Interval in EKG and Sudden Death
Interventions Drug: Progesterone
Drug: Placebo
Drug: Ibutilide
Enrollment 19
Recruitment Details Subjects recruited from a) INResearch database, maintained by Indiana Clinical Translational Research Institute (CTSI), and b) Hard copy and electronic advertisements on the IUPUI and Purdue University campuses Participants were recruited between October 2012 and February 2014
Pre-assignment Details n=333 subjects assessed for eligibility; n=27 consented, n=306 excluded (n=108 did not meet inclusion criteria, n=198 declined to participate); of n=27 consented, n=19 enrolled, n=8 excluded because they met one or more exclusion criteria
Arm/Group Title Progesterone First, Then Placebo Placebo First, Then Progesterone
Hide Arm/Group Description

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Period Title: Intervention 1
Started 10 [1] 9
Returned for 1st Ibutilide Administratio 7 9
Completed 7 9
Not Completed 3 0
Reason Not Completed
Lost to Follow-up             2             0
Nonadherent to study medications             1             0
[1]
Number of patients randomized to receive progesterone first
Period Title: Intervention 2
Started 7 9
Returned for 2nd Ibutilide Administratio 7 8
Completed 7 8
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
Arm/Group Title Entire Study Population
Hide Arm/Group Description n=15 subjects who completed the study
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
Includes n=15 subjects included in the final analysis. Includes subjects randomized to receive progesterone first and patients randomized to receive placebo first
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
29  (5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
15
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
1.Primary Outcome
Title Baseline (Pre-Ibutilide) QTcI Intervals
Hide Description [Not Specified]
Time Frame After 7 days of progesterone or placebo, prior to receiving IV ibutilide
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: ms
412  (15) 419  (14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
2.Primary Outcome
Title Maximum Individual-corrected QT Interval (QTcI)
Hide Description 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.
Time Frame 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours post-ibutilide administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: ms
443  (17) 458  (19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
3.Primary Outcome
Title Maximum % Change From Baseline in QTcI Intervals Following Ibutilide Administration
Hide Description [Not Specified]
Time Frame After 7 days of progesterone or placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline value
7.5  (2.4) 9.3  (3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
4.Primary Outcome
Title Area Under the QTcI - Time Curve (AUEC)
Hide Description [Not Specified]
Time Frame From beginning of 10-minute ibutilide infusion to 1 hour following ibutilide infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: ms*hr
497  (13) 510  (16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
5.Secondary Outcome
Title Incidence of Progesterone-associated Adverse Effects Compared to Placebo
Hide Description [Not Specified]
Time Frame During 7 days of treatment with oral progesterone or placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 16 17
Measure Type: Number
Unit of Measure: percentage of participants
Fatigue/general malaise 38 6
Headache 13 6
Mood changes 13 0
Breast tenderness 13 0
Hypotension 6 0
Vertigo requiring discontinuation 6 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments P value for incidence of fatigue/malaise
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments p values for incidence of headache
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments p value for incidence of mood changes
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments p value for incidence of breast tenderness
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments p value for incidence of hypotension
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments p value for incidence of vertigo requiring discontinuation of therapy
Method Fisher Exact
Comments [Not Specified]
6.Other Pre-specified Outcome
Title Adverse Effects Associated With Ibutilide in the Progesterone and Placebo Phases
Hide Description [Not Specified]
Time Frame Within 8 hours following ibutilide administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 17
Measure Type: Number
Unit of Measure: percentage of participants
Bradycardia (HR < 60 bpm) 20 12
Burning at infusion site 7 6
Transient QTc interval > 500 ms 0 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments p value for bradycardia
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.99
Comments p value for burning at infusion site
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > 0.99
Comments p value for transient QTc interval > 500 ms
Method Fisher Exact
Comments [Not Specified]
7.Other Pre-specified Outcome
Title Maximum (Peak) Serum Ibutilide Concentrations During Progesterone and Placebo Phases
Hide Description [Not Specified]
Time Frame Within 1 hour following ibutilide administration (0, 15 & 30 minutes and 1 hours.)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: pg/mL
1247  (770) 1172  (709)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
8.Other Pre-specified Outcome
Title Serum Estradiol Concentrations During the Progesterone and Placebo Phases
Hide Description [Not Specified]
Time Frame Following 7 days of progesterone or placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: pg/mL
89.3  (62.8) 71.8  (31.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
9.Other Pre-specified Outcome
Title Serum Progesterone Concentrations During Progesterone and Placebo Phases
Hide Description [Not Specified]
Time Frame After 7 days of progesterone or placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: ng/mL
16.2  (11.0) 1.2  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
10.Other Pre-specified Outcome
Title Ratio of Serum Progesterone:Estradiol Concentrations During the Progesterone and Placebo Phases
Hide Description [Not Specified]
Time Frame After 7 days of progesterone or placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: Ratio
205  (40) 18  (16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test
Time Frame During 7 days of therapy with progesterone or placebo
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description

Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days

Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days

All-Cause Mortality
Progesterone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Progesterone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/16 (6.25%)      0/17 (0.00%)    
Ear and labyrinth disorders     
Vertigo requiring discontinuation of therapy   1/16 (6.25%)  1 0/17 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Progesterone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/16 (56.25%)      2/17 (11.76%)    
Endocrine disorders     
Breast tenderness   2/16 (12.50%)  2 0/17 (0.00%)  0
General disorders     
Fatigue/general malaise   6/16 (37.50%)  6 1/17 (5.88%)  1
Headache   2/16 (12.50%)  2 1/17 (5.88%)  1
Mood changes   2/16 (12.50%)  2 0/17 (0.00%)  0
Hypotension   1/16 (6.25%)  1 0/17 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. James E Tisdale
Organization: Indiana University
Phone: 317-880-5418
Responsible Party: James E. Tisdale, Purdue University
ClinicalTrials.gov Identifier: NCT01929083     History of Changes
Other Study ID Numbers: 12GRNT12060187
First Submitted: August 22, 2013
First Posted: August 27, 2013
Results First Submitted: August 27, 2015
Results First Posted: September 28, 2015
Last Update Posted: October 30, 2015