Effect of Fimasartan for Modification of Atheroma Vulnerability in DEFERred Coronary Disease (FIMA-DEFER)

A Randomized, Double-blind Study of Effect of Fimasartan for Modification of Atheroma Vulnerability in DEFERred Coronary Disease

• Fimasartan will be more beneficial in stabilizing the plaque vulnerability compared to control group in deferred coronary lesions.
• Fimasartan will be more beneficial in reducing total plaque volume compared to control group in deferred coronary lesions.
• Fimasartan will be more beneficial in reducing functional impairment of stenotic lesions (assessed by FFR:Fractional Flow Reserve) in deferred coronary lesions.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Fimasartan; Drug: Placebo

Detailed Description

Prospective, double-blind, randomized clinical study with enrollment of patients over at least 18 years of age who require coronary angiography for a clinical indication with hypertension defined as systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg. Inclusion requires at least one deferred coronary lesion with 1) visually-estimated angiographic %diameter stenosis 20-50% or 2) %diameter stenosis >50% without any evidence of inducible ischemia. The target vessel for IVUS interrogation must not have undergone angioplasty (deferred lesion) nor have more than 50% luminal narrowing throughout a target segment. Patients meeting inclusion criteria without any exclusion criteria will be randomized 1:1 (Fimasartan 60-120 mg vs placebo). All subjects will be followed up at 1 year for serial VH-IVUS and conventional IVUS evaluation. Also, OCT sub-study will be performed in selected patients with lesions at least 20 mm distally located from coronary ostium. All patients will be blindly assigned to control and Fimasartan once daily as 1:1 ratio and are prescribed for 1year.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gwangju, Korea, Republic of, 501-757
    • Chonnam National University Hospital
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Ulsan, Korea, Republic of, 682-714
    • Ulsan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 84 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hypertensive patients (systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg) or medically treated hypertension with normal blood pressure who undergo coronary angiography with clinical indications
2. 18 < Age < 85
3. Patient who has received informed consent
4. at least one deferred coronary lesion with 1) visually-estimated angiographic %diameter stenosis 20-50% or 2) %diameter stenosis >50% without any evidence of inducible ischemia (FFR ≥ 0.8 or negative perfusion defect on thallium scan or negative treadmill test)

Exclusion Criteria:

1. Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy) or planned major non-cardiac surgery within the study period
2. Planned performance of PCI or CABG in the target vessel or its branches containing the index
3. Evidence of congestive heart failure, or left ventricular ejection fraction < 40%
4. Stroke or resuscitated sudden death in the past 6 months
5. Chronic disease requiring treatment with oral, intravenous, or intra-articular corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible)
6. A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer
7. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study
8. Significant renal disease manifested by serum creatinine > 1.5 mg/dL
9. Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal)
10. Active hepatitis B or C or carrier
11. Hypotension (systolic blood pressure <90 mmHg)
12. Patients already taking ACE inhibitors or ARBs
13. Patients with STEMI requiring primary PCI
14. Patients pregnant or breast-feeding or child-bearing potential
15. Patients who are lack of intention for effective contraception
16. Patients with history of previous enrollment into a clinical trials within 3 months
17. Allergic or contraindicated to Angiotensin II antagonists
18. History of any arterial bypass or angioplastic intervention involving the target vessel
19. Luminal narrowing in the left main > 50% by visual inspection of angiogram
20. Visually-estimated angiographic reference segment diameter of <2.75mm or >4.0 mm
21. Presence of thrombus or complex plaque morphology in the target vessel that suggests a high likelihood of distal embolism
22. Severe tortuosity of the target vessel or any other anatomical reasons that the investigator deems
23. Inappropriate for IVUS procedures. Vessel with thrombus (on GS-IVUS), moderate or severe calcification, angulation
24. Culprit vessel in AMI
25. RWMA (Regional Wall Motion Abnormality) or scar tissue in the territory subtended by the studied lesion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fimasartan; Initial dose will be started with 60mg per day. At 4 week follow-up after the procedure, dose titration upto 120 mg per day will be made if the patient is not hypotensive.	Drug: Fimasartan; 60-120mg/day (target dose) of Fimasartan will be administered for the study period (till the follow-up angiography); Other Names: Kanarb Tab.
Placebo Comparator: Placebo; Initial dose will be started with 60mg per day. At 4 week follow-up after the procedure, dose titration upto 120 mg per day will be made if the patient is not hypotensive.	Drug: Placebo; 60-120mg/day (target dose) of Placebo will be administered for the study period (till the follow-up angiography)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in percent necrotic core (NC) volume of plaque by VH (Virtual Histology) in the "target segment" (within deferred vessel)	baseline and 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Change of total atheroma volume (TAV) and percent atheroma volume (PAV) of the target segment and the most diseased 10-mm segment (normalized to different segment length) with the largest plaque volume	baseline and 1 year
Percent change in minimal lumen area (MLA) in target segment	baseline and 1 year
Change of absolute area or percentages (%) of each plaque VH composition (fibrotic, fibrofatty, dense calcium, necrotic core) at minimal lumen area (MLA) and largest necrotic core area within the target segment	baseline and 1 year
Change of VH-IVUS (Intra Vascular UltraSound) detected plaque type from baseline	at 1 year
Change of percentage (%) of OCT (Optical Coherence Tomography)-defined TCFA (Thin Cap Fibrotic Atheroma) within the target segment from baseline	at 1 year
Change of composition of OCT-defined fibrous, fibro-calcific, and lipid-rich plaque within the target segment	baseline and 1 year
Change of OCT-defined fibrous cap thickness, the presence of plaque disruption, calcification or intraluminal thrombus within the target segment	baseline and 1 year
Change of FFR in target segment from baseline	at 1 year
systolic and diastolic blood pressure	at 1 year follow-up
Change in high sensitive CRP (C-Reactive Protein)from baseline	at 1 year

Collaborators and Investigators

• Sponsor: Seung-Jung Park
• Collaborators: CardioVascular Research Foundation, Korea; Boryung Pharmaceutical Co., Ltd

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: June 24, 2011
• First Submitted That Met QC Criteria: June 28, 2011
• First Posted (Estimate): June 29, 2011

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Coronary Artery Disease; Coronary Disease; Plaque, Atherosclerotic
• Other Study ID Numbers: CVRF2011-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is not a publicly funded trial.