Evaluate the Efficacy and Safety of Pletaal (Cilostazol) in Subjects With Vasospastic Angina (STELLA)

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)

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).

Study Overview

• Status: Completed
• Conditions: Variant Angina
• Intervention / Treatment: Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • DaeJeon, Korea, Republic of
    • ChungNam Univ. Hospital
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Medical Center
  • Gangneung, Korea, Republic of
    • GangNeung Asan Hospital
  • Gwangju, Korea, Republic of
    • Chonnam National University Hospital
  • Jinjoo, Korea, Republic of
    • Gyongsang National University Hospital
  • Pusan, Korea, Republic of
    • Dong-A University Hospital
  • Pusan, Korea, Republic of
    • Pusan National University Yansan Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Suwon, Korea, Republic of
    • Ajou University Hospital
  • Ulsan, Korea, Republic of
    • Ulsan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cilostazol; 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).	Drug: Placebo; 2 weeks treatment of Cilostazol 100mg, or placebo oral tablets bid after 2 weeks treatment of Cilostazol 50mg, or placebo oral tablets bid (Total 4 weeks); Other Names: Amlodipine; Nitroglycerin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change of the chest pain frequency	Collect the chest pain frequency data related with vasospastic angina episodes by subject diaries. Descriptive statistics (N, mean, standard deviation, minimum, median and maximum) will be presented by treatment group. ANCOVA will be performed between the treatment groups using the baseline (a week before IP dosing) as covariate.	A week before IP dosing and the final a week after IP dosing (average 6weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The chest pain frequency, the pain intensity, nitroglycerin consumption of the final a week after IP dosing from a week before IP dosing	Descriptive statistics (N, mean, standard deviation, minimum, median and maximum) will be presented by treatment group. ANCOVA will be performed between the treatment groups using the baseline (a week before IP dosing) as covariate. The subject who has no chest pain will be regarded as the total pain intensity and the average pain intensity are '0'. The subject who has taken no nitroglycerin will be regarded as taking '0' tablet.	A week before IP dosing and the final a week after IP dosing (average 6weeks)

Collaborators and Investigators

• Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: June Hong Kim, MD, Pusan National University Yansan Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 27, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimate): October 3, 2011

Study Record Updates

• Last Update Posted (Estimate): July 16, 2012
• Last Update Submitted That Met QC Criteria: July 13, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Cilostazol; Variant angina
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina, Unstable; Angina Pectoris; Angina Pectoris, Variant; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine; Nitroglycerin
• Other Study ID Numbers: STELLA (Other Identifier: Baylor College of Medicine)