Trial Outcomes & Findings for Responses of Myocardial Ischemia to Escitalopram Treatment (NCT NCT00574847)

NCT ID: NCT00574847

Last Updated: 2015-08-05

Results Overview

MSIMI is defined by the following: compared to rest, 1) any development of new abnormal wall motion; 2) reduction of LVEF 8% and/or; 3) deviation (depression or elevation) of ST-segment of ECG in 2 or more leads lasting for 3 consecutive beats, occurring during at least one of the 3 mental stress tasks.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 127 participants
• Primary outcome timeframe: Week 6
• Results posted on: 2015-08-05

Participant Flow

We screened all patients with Coronary Heart Disease (CHD) who visited Duke cardiology clinics. Patients 21 years or older were eligible to participate if they had CHD, as documented by angiographic findings of coronary artery stenosis of 70% or greater, history of MI, or history of cardiac revascularization.

25527 underwent initial screening. 22833 excluded due to reasons including no CHD, atrial fibrillation/arrhythmia, psychiatric disorder, and LVEF less than 30%. 2294 did not provide consent. 65 excluded due to medical conditions. 203 excluded due to no MSIMI or inability to undergo mental stress testing. 5 more declined to undergo randomization.

Participant milestones

Measure	Escitalopram Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Overall Study STARTED	64	63
Overall Study COMPLETED	56	56
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Measure	Escitalopram Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Overall Study Adverse Event	2	0
Overall Study Death	1	0
Overall Study Withdrawal by Subject	2	2
Overall Study Physician Decision	1	0
Overall Study Did not receive medication (declined)	2	5

Baseline Characteristics

Responses of Myocardial Ischemia to Escitalopram Treatment

Baseline characteristics by cohort

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Total n=127 Participants Total of all reporting groups
Age, Continuous	66.5 years STANDARD_DEVIATION 9.3 • n=5 Participants	61.4 years STANDARD_DEVIATION 11.5 • n=7 Participants	64.0 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	48 Participants n=7 Participants	101 Participants n=5 Participants
History of Depression	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 6

Population: Intent-to-treat (ITT)

MSIMI is defined by the following: compared to rest, 1) any development of new abnormal wall motion; 2) reduction of LVEF 8% and/or; 3) deviation (depression or elevation) of ST-segment of ECG in 2 or more leads lasting for 3 consecutive beats, occurring during at least one of the 3 mental stress tasks.

Outcome measures

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Percentage of Participants With an Absence of Mental Stress-induced Myocardial Ischemia (MSIMI) During the 3 Mental Stressors	34.2 percentage of participants Interval 31.6 to 36.8	17.5 percentage of participants Interval 15.4 to 19.6

PRIMARY outcome

Timeframe: week 6

Population: Subjects who completed.

MSIMI is defined by the following: compared to rest, 1) any development of new abnormal wall motion; 2) reduction of LVEF 8% and/or; 3) deviation (depression or elevation) of ST-segment of ECG in 2 or more leads lasting for 3 consecutive beats, occurring during at least one of the 3 mental stress tasks.

Outcome measures

Measure	Escitalopram n=56 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=56 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Percentage of Participants With Overall Mental Stress-induced Myocardial Ischemia (MSIMI)	66.1 percentage of participants	83.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, week 6

Population: ITT, 9 subjects excluded from analysis due to missing data.

Blood pressure will be measured the last 3 minutes of the 20 minute calibration period (resting), every minute during the 3 minutes mental stress testing, the last 3 minutes of the 6 minute rest periods between mental stress testing, and every minute during and after the physical stress testing with an automatic oscillometric blood pressure monitor (Quinton Electronics). Mental Stress Induced Change of Systolic Blood Pressure will be calculated by taking the mean of the mental stress systolic blood pressure measurements minus the resting Systolic blood pressure. End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=62 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=56 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Mental Stress Induced Change of Systolic Blood Pressure	19.3 mm Hg Interval 16.7 to 22.0	23.6 mm Hg Interval 20.8 to 26.4

SECONDARY outcome

Timeframe: Baseline, week 6

Population: ITT, 9 subjects excluded from the analysis due to missing data.

Blood pressure will be measured the last 3 minutes of the 20 minute calibration period (resting), every minute during the 3 minutes mental stress testing, the last 3 minutes of the 6 minute rest periods between mental stress testing, and every minute during and after the physical stress testing with an automatic oscillometric blood pressure monitor (Quinton Electronics). Mental Stress Induced Change of Diastolic Blood Pressure will be calculated by taking the mean of the mental stress Diastolic blood pressure measurements minus the resting Diastolic blood pressure. End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=62 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=56 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Mental Stress Induced Change of Diastolic Blood Pressure	11.4 mm Hg Interval 9.5 to 13.4	12.2 mm Hg Interval 10.1 to 14.2

SECONDARY outcome

Timeframe: Baseline to week 6

Outcome measures

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Percentage of Participants With Adverse Events	71.9 percentage of participants	44.4 percentage of participants

SECONDARY outcome

Timeframe: 6 week

Population: ITT

The Beck Depression Inventory II (BDI-II) is a 21 question, self-administered measure of depressive symptoms. Score range, 0 to 63 (higher score=greater severity of depressive symptoms). End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Beck Depression Inventory	7.4 units on a scale Interval 6.3 to 8.6	7.0 units on a scale Interval 5.8 to 8.2

SECONDARY outcome

Timeframe: baseline, 6 weeks

Population: ITT, 10 subjects excluded from analysis due to missing data.

A standard 12-lead Electrocardiograph (ECG) will be recorded at 1-minute intervals during the last 3 minutes of each rest period, the 3 minutes of the mental stress testing, and during exercise testing. Heart rate will be determined from the ECGs.

Mental Stress Induced Change in heart rate will be calculated by taking the mean of the mental stress heart rate measurements minus the resting heart rate measurements. End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=61 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=56 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Mental Stress Induced Change in Heart Rate	6.34 beats/minute Interval 5.0 to 7.7	9.1 beats/minute Interval 7.8 to 10.5

SECONDARY outcome

Timeframe: week 6

Population: ITT, 29 subjects excluded from analysis due to missing data.

End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=48 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=50 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
5HTT, Serotonin Transporter Protein	139.7 fmol/mg Interval 126.1 to 153.4	160.4 fmol/mg Interval 147.0 to 173.7

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT, 27 subjects were excluded from analysis due to missing data.

End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=50 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=50 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Platelet Serotonin Binding Affinity Kd_100	4202.4 nM Interval 3328.6 to 5076.2	210.1 nM Interval 0.0 to 1083.9

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT

Score range, 10 to 50 (higher score = greater levels of perceived stress). End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Perceived Stress Scale	21.4 units on a scale Interval 20.3 to 22.5	21.8 units on a scale Interval 20.6 to 22.9

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT, 1 subject excluded from analysis due to missing data.

Score ranges: hostility, 0 to 27 (higher score=greater levels of hostility)/ End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=62 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Cook-Medley Hostility (Ho) Scale	9.9 units on a scale Interval 9.1 to 10.7	10.3 units on a scale Interval 9.5 to 11.1

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT, 1 subject excluded from analysis due to missing data.

hostile affect, 0 to 5 (higher score=greater levels of hostile affect). End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=62 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Cook-Medley Hostility (Ho) Hostile Affect Sub-scale	1.6 units on a scale Interval 1.3 to 1.8	1.8 units on a scale Interval 1.6 to 2.1

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT

STAI measures anxiety. The questionnaire asks the patients how they feel and allows them to respond on a frequency scale that ranges from 1(not at all) to 4(almost always/very much so). Scores range from 20-80 and the higher the score the greater the anxiety level. This applies to both the Trait and State scales. End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=64 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Spielberger State-Trait Anxiety Inventory Scales (STAI) Trait	31.2 units on a scale Interval 29.7 to 32.6	32.0 units on a scale Interval 30.5 to 33.4
Spielberger State-Trait Anxiety Inventory Scales (STAI) State	27.9 units on a scale Interval 26.4 to 29.4	29.5 units on a scale Interval 28.0 to 31.1

SECONDARY outcome

Timeframe: 6 week

Population: ITT, 7 subject excluded from analysis due to missing data.

End point values adjusted for baseline values age and sex.

Outcome measures

Measure	Escitalopram n=59 Participants Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=61 Participants Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Exercise Stressed-induced Myocardial Ischemia (ESIMI)	45.8 percentage of change Interval 36.6 to 55.0	52.5 percentage of change Interval 43.3 to 61.8

Adverse Events

Escitalopram

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Escitalopram n=64 participants at risk Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 participants at risk Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
Nervous system disorders Confusion, Hallucination	1.6% 1/64	0.00% 0/63
Cardiac disorders Death	1.6% 1/64	0.00% 0/63
Cardiac disorders unstable angina	1.6% 1/64	1.6% 1/63

Other adverse events

Measure	Escitalopram n=64 participants at risk Escitalopram: Dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.	Placebo n=63 participants at risk Placebo: Placebo dosage will range from 5 mg to 20 mg once a day for the duration of the study (6 weeks). Tablets are in 5 mg or 10 mg form, depending upon the dosage the patient is prescribed.
General disorders fatigue	29.7% 19/64	14.3% 9/63
Skin and subcutaneous tissue disorders burning sensation	1.6% 1/64	0.00% 0/63
Nervous system disorders CNS symptom	26.6% 17/64	20.6% 13/63
Gastrointestinal disorders constipation	28.1% 18/64	17.5% 11/63
Musculoskeletal and connective tissue disorders cramping in legs	4.7% 3/64	3.2% 2/63
Cardiac disorders irregular heartbeat	0.00% 0/64	3.2% 2/63
Reproductive system and breast disorders sexual dysfunction	15.6% 10/64	6.3% 4/63
Infections and infestations sinusitis	1.6% 1/64	0.00% 0/63

Additional Information

Wei Jiang, MD

Duke University Medical Center

Phone: 919-668-0762

Email: jiang001@mc.duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place