Clinical trial NCT01444885: Evaluate the Efficacy and Safety of Pletaal (Cilostazol) in Subjects With Vasospastic Angina
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Therapeutic Exploratory Study to Evaluate the Efficacy and Safety of PletaalÒ(Cilostazol) in Subjects With Vasospastic Angina (STELLA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Variant Angina
Keywords: Variant angina
Cilostazol
Lead sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2011-10-03
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to investigate the efficacy and safety of Pletaal (Cilostazol) in comparison with placebo for 4 weeks in vasospastic angina patients who have an insufficient response to Amlodipine (Calcium channel blocker).

Detailed description: A Multicenter, Randomized, Double-Blind, Placebo-controlled, Parallel group, Therapeutic exploratory Study.

The subject who has at least an episode of chest pain weekly despite Amlodipine 5mg once a day (qd) taking during 2 weeks will have treatment of Pletaal (Cilostazol) or Placebo for 4 weeks. Pletaal (Cilostazol) is taken 100mg oral tablets two times a day (bid) during 2 weeks after dosing of Pletaal (Cilostazol) 50mg oral tablets bid during 2 weeks. Placebo of Pletaal (Cilostazol) is used as the control medication.

Eligibility criteria: Inclusion Criteria:

1. Male or female over the age of 20 and under the age of 80
2. Diagnosis of vasospastic angina
3. At least one episode of chest pain weekly during the Amlodipine run in period for 2 weeks

Exclusion Criteria:

1. Currently taking or has taken Cilostazol within the last 3 month before the screening.
2. Taking oral antiplatelet agents such as Aspirin, Clopidogrel after Amlodipine run-in period.
3. Oral anticoagulants such as Warfarin within the last a month before the screening.
4. Currently taking any of the following medications or has taken any of the following medications within the last a week before the screening:

   * Other Calcium channel blockers than Amlodipine
   * Beta-blocker, or Alpha-blocker
   * Oral Nitrate, Nicorandil, except sublingual Nitroglycerin as required(PRN)
   * Vitamin E preparations
   * Estrogens
5. History of Myocardial infarction or Myocardial infarction by vasospastic angina at screening
6. History of life threatening vasospastic events such as ventricular tachycardia , ventricular fibrillation, or syncope
7. History of stroke, intracranial hemorrhage, or Transient Ischemic Attack(TIA)
8. Hemorrhage (hemophilia, capillary fragility, intracranial hemorrhage, upper gastrointestinal hemorrhage, urinary hemorrhage, hemoptysis, vitreous hemorrhage, etc.) or such tendency (active peptic ulcer, hemorrhagic stroke within past 6 months, a case hemorrhage is suspected by wound for surgery within 3 months, proliferative diabetic retinopathy and uncontrolled hypertension)
9. History of clinically significant hypersensitivity to the substances of Cilostazol, Amlodipine, Nitroglycerin or dihydropyridine
10. Patients with severe aortic valvular stenosis
11. History of shock
12. Hypotension of diastolic pressure \< 90 mmHg at screening
13. History of clinically significant hypersensitivity to the substances of Nitrates
14. Patients with severe anemia of Hemoglobin ≤ 6.5 g/dl at screening
15. History of glaucoma
16. Electrocardiogram(ECG) abnormality precluding interpretation of ST change at screening
17. Congestive heart failure with less than 40% of left ventricular ejection fraction within the last 3 month before the screening or screening period
18. Atrial fibrillation or valvular heart disease, more than moderate severity
19. Suspected or identified spasm of left main coronary artery, result of coronary angiography or coronary angiography in the ergonovine induced coronary spasm provocation test
20. History of Coronary artery bypass graft(CABG) or percutaneous coronary intervention(PCI)
21. Tachycardia; Heart rate \> 100 bpm, at Screening
22. Uncontrolled hypertension, defined as ≥ 160 mmHg systolic or ≥ 100 mmHg diastolic at Screening
23. Creatinine ≥ 1.5 mg/dL at screening
24. Aspartate transaminase (AST) or alanine transaminase (ALT) \> 3 times the upper limit of normal (ULN) at screening
25. Platelet \< 100,000 mm3 at screening
26. QT prolongation defined as baseline QTc \> 450 msec for males or \> 470 msec for females at Screening.
27. Women who have the possible of pregnancy, or positive urine or blood pregnancy test at screening
28. Women who are not using a reliable method of birth control, who are pregnant, or who are breast-feeding
29. Drug compliance of Amlodipine \< 80% during the Amlodipine run in period for 2 weeks
30. Otherwise judged by the investigator to be inappropriate for inclusion in the trial.

Primary outcomes:
measure: Percent change of the chest pain frequency
timeFrame: A week before IP dosing and the final a week after IP dosing (average 6weeks)
Secondary outcomes:
measure: The chest pain frequency, the pain intensity, nitroglycerin consumption of the final a week after IP dosing from a week before IP dosing
timeFrame: A week before IP dosing and the final a week after IP dosing (average 6weeks)
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: DaeJeon
country: Korea, Republic of
facility: ChungNam Univ. Hospital
city: Gangneung
country: Korea, Republic of
facility: Gangneung Asan Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Jinjoo
country: Korea, Republic of
facility: Gyongsang National University Hospital
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Yansan Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
Study officials:
affiliation: Pusan National University Yansan Hospital
name: June Hong Kim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shin ES, Lee JH, Yoo SY, Park Y, Hong YJ, Kim MH, Lee JY, Nam CW, Tahk SJ, Kim JS, Jeong YH, Lee CW, Shin HK, Kim JH. A randomised, multicentre, double blind, placebo controlled trial to evaluate the efficacy and safety of cilostazol in patients with vasospastic angina. Heart. 2014 Oct;100(19):1531-6. doi: 10.1136/heartjnl-2014-305986. Epub 2014 Jun 16.