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

Purpose

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.

Condition	Intervention	Phase
Coronary Artery Disease	Drug: Fimasartan Drug: Placebo	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind Study of Effect of Fimasartan for Modification of Atheroma Vulnerability in DEFERred Coronary Disease

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease

U.S. FDA Resources

Further study details as provided by CardioVascular Research Foundation, Korea:

Primary Outcome Measures:

Change in percent necrotic core (NC) volume of plaque by VH (Virtual Histology) in the "target segment" (within deferred vessel) [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
Percent change in minimal lumen area (MLA) in target segment [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
Change of VH-IVUS (Intra Vascular UltraSound) detected plaque type from baseline [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
Change of percentage (%) of OCT (Optical Coherence Tomography)-defined TCFA (Thin Cap Fibrotic Atheroma) within the target segment from baseline [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
Change of composition of OCT-defined fibrous, fibro-calcific, and lipid-rich plaque within the target segment [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
Change of OCT-defined fibrous cap thickness, the presence of plaque disruption, calcification or intraluminal thrombus within the target segment [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
Change of FFR in target segment from baseline [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
systolic and diastolic blood pressure [ Time Frame: at 1 year follow-up ] [ Designated as safety issue: No ]
Change in high sensitive CRP (C-Reactive Protein)from baseline [ Time Frame: at 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	354
Study Start Date:	July 2011
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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) Other Name: 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.

Eligibility

Ages Eligible for Study:	19 Years to 84 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
18 < Age < 85
Patient who has received informed consent
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:

Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy) or planned major non-cardiac surgery within the study period
Planned performance of PCI or CABG in the target vessel or its branches containing the index
Evidence of congestive heart failure, or left ventricular ejection fraction < 40%
Stroke or resuscitated sudden death in the past 6 months
Chronic disease requiring treatment with oral, intravenous, or intra-articular corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible)
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
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
Significant renal disease manifested by serum creatinine > 1.5 mg/dL
Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal)
Active hepatitis B or C or carrier
Hypotension (systolic blood pressure <90 mmHg)
Patients already taking ACE inhibitors or ARBs
Patients with STEMI requiring primary PCI
Patients pregnant or breast-feeding or child-bearing potential
Patients who are lack of intention for effective contraception
Patients with history of previous enrollment into a clinical trials within 3 months
Allergic or contraindicated to Angiotensin II antagonists
History of any arterial bypass or angioplastic intervention involving the target vessel
Luminal narrowing in the left main > 50% by visual inspection of angiogram
Visually-estimated angiographic reference segment diameter of <2.75mm or >4.0 mm
Presence of thrombus or complex plaque morphology in the target vessel that suggests a high likelihood of distal embolism
Severe tortuosity of the target vessel or any other anatomical reasons that the investigator deems
Inappropriate for IVUS procedures. Vessel with thrombus (on GS-IVUS), moderate or severe calcification, angulation
Culprit vessel in AMI
RWMA (Regional Wall Motion Abnormality) or scar tissue in the territory subtended by the studied lesion

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384747

Contacts

Contact: Seung-Jung Park, MD, PhD	82-2-3010-4812	sjpark@amc.seoul.kr
Contact: Sujin Kang, MD, PhD	82-2-3010-3157	sjkang@amc.seoul.kr

Locations

Korea, Republic of
Chonnam National University Hospital	Recruiting
Gwangju, Korea, Republic of, 501-757
Contact: Young-Jun Hong, MD.,PhD. 82-10-2055-7919 myungho@chollian.net
Principal Investigator: Young-Jun Hong, MD.,PhD.
Asan Medical Center	Recruiting
Seoul, Korea, Republic of, 138-736
Principal Investigator: Seung-Jung Park, MD.,PhD.
Ulsan University Hospital	Recruiting
Ulsan, Korea, Republic of, 682-714
Contact: Eun-Seok Shin, MD.,PhD. 82-10-6319-4025 sesim98@yahoo.co.kr
Principal Investigator: Eun-Seok Shin, MD.,PhD.

Sponsors and Collaborators

Seung-Jung Park

CardioVascular Research Foundation, Korea

Boryung Pharmaceutical Co., Ltd

Investigators

Principal Investigator:

Seung-Jung Park, MD, PhD

Asan Medical Center

More Information

No publications provided

Responsible Party:	Seung-Jung Park, MD,PhD, Chairman,Heart Institute, Asan Medical Center,University of Ulsan,College of Medicine, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier:	NCT01384747 History of Changes
Other Study ID Numbers:	CVRF2011-03
Study First Received:	June 24, 2011
Last Updated:	August 7, 2012
Health Authority:	Korea: Food and Drug Administration

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Plaque, Atherosclerotic
Heart Diseases

Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on May 21, 2013