UMIN-CTR Clinical Trial

Basic information
Public title	Standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy
Acronym	Standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy (EMPATHY)
Scientific Title	Standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy
Scientific Title:Acronym	Standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy (EMPATHY)
Region	Japan

Condition
Condition	Hypercholesterolemia complicated with diabetic retinopathy
Classification by specialty	Cardiology Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigate the efficacy of standard/intensive lipid-control therapies in patients with hypercholesterolemia complicated with diabetic retinopathy without history of coronary arterial diseases treated with statin monotherapy, using onset of cardiovascular diseases/death as an endpoint. In addition, to investigate the safety of standard/intensive lipid-control therapies using incidence rates of adverse events.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Not applicable

Assessment
Primary outcomes	Lipid-control will be conducted with statin monotherapy in patients with hypercholesterolemia complicated with diabetic retinopathy. Using time until the onset of cardiovascular diseases/death as an endpoint, it will be determined whether the inhibitory effect of the intensive lipid-control therapy on the onset of cardiovascular diseases is superior to that of the standard one. Cardiovascular diseases include the following: - cardiac event: MI, unstable angina pectoris requiring unscheduled hospitalization, coronary revascularization (PTCA, CABG) - cerebral event: cerebral infarction, cerebrovascular revascularization - Renal event: initiation of permanent dialysis, 2-fold or more increase in serum creatinine (and > 1.5 mg/dL) - vascular event: aortic/peripheral arterial diseases (onset of aortic dissection, mesenteric artery thrombosis, or arteriosclerosis obliterans-related severe ischemia (ulcer) of lower limbs, or finger/leg amputation)
Key secondary outcomes	1) Efficacy will be assessed using the following evaluation parameters: - total deaths - onset of individual cardiac, cerebral, renal, vascular events - onset of stroke (cerebral infarction, cerebral hemorrhage, subarachnoid haemorrhage) - changes (measured value, rate) in CKD-related parameters (eGFR, urinary albumin, urinary protein) 2) Safety of the therapies will be evaluated using incidence rates of adverse events as an evaluation parameter.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Intensive lipid-control therapy group: LDL-C <70 mg/dL Observation period: 2-5.5 years
Interventions/Control_2	Standard lipid-control therapy group: LDL-C 100 <= LDL-C < 120 mg/dL Observation period: 2-5.5 years
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	30 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients who satisfy all of the following criteria will be included. At interim registration: 1) patients who give written consent to participation in the study at their own will 2) at the age of 30 years or above (at consent acquisition) 3) male or female (except females with possibility of pregnancy) 4) Inpatient / outpatient: outpatient 5) patients with hypercholesterolemia whose LDL-C is 120 mg/dL or more for treatment-naive patients or 100 mg/dL or more for patients with experience of monotherapy using statins (in case of patients with atorvastatin, pitavastatin, or rosuvastatin, they must be treated with up to 10mg/day, 2mg/day, 2.5mg/day, respectively) or lipid-lowering drugs 6) patients with type II diabetes 7) patients with no history of coronary arterial diseases (MI, angina pectoris, coronary revascularization). At official registration: 1) patients with diabetic retinopathy
Key exclusion criteria	Patients to whom any of the following criteria apply will be excluded from the study: at interim registration: 1) patients with history of hypersensitivity to statins 2) patients with history of drug-induced muscle disorder 3) patients with history of coronary arterial diseases (MI, angina pectoris, coronary revascularization) 4) patients with history of stroke (including revascularization) 5) patients complicated with symptomatic PAD (Fontaine class II or above) 6) hypertensive patients with diastolic BP of 120 mmHg or more or systolic BP of 200 mmHg or more, or patients with hypertensive emergency 7) patients with NYHA functional class IIM or more 8) patients with cardiac valvulopathy who have serious hemodynamic abnormality 9) patients under treatment with at least 2 different lipid-lowering drugs 10) patients with familial hypercholesterolemia 11) patients with serious complications e.g. malignant tumors or patients with limited life expectancy (however, patients who are decided free of relapse without treatment of malignant tumors over five years before obtaining their informed consent are able to be enrolled) 12) patients with renal transplant or patients under dialysis 13) patients who are pregnant or who are at risk of pregnancy, or those who desire to become pregnant during their participation in the study 14) other patients deemed unsuitable by the principal investigator or investigator. At official registration: The study will be discontinued in patients who have undergone prespecified examinations during the observation period and satisfy any of the following criteria: 1) patients with apparent ischemia in ECG at rest 2) patients with AST of 100 IU/L or above or ALT of 100 IU/L or above 3) patients with serum creatinine of 2.0 mg/dL or more or eGFR of 30 mL/min/1.73 m2 or less 4) patients with nephrotic syndrome 5) patients with serum triglyceride of 1000 mg/dL or more 6) other patients deemed unsuitable by the principal investigator or investigator.
Target sample size	5000

Research contact person
Name of lead principal investigator	1st name Middle name Last name Issei Komuro, Hiroshi Ito
Organization	Tokyo University Graduate School of Medicine Keio University School of Medicine
Division name	Cardiovascular Medicine, Medicine I, Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine
Zip code
Address	7-3-1, Hongo, Bunkyo-ku, Tokyo, 35 Shinanomachi, Shinjuku-ku, Tokyo
TEL	0120-203-488
Email	empathy@mebix.co.jp

Public contact
Name of contact person	1st name Middle name Last name Makoto Sawaguchi
Organization	EMPATHY Study group
Division name	EMPATHY Study group
Zip code
Address	1-11-44 Akasaka, Minato-ku, Tokyo
TEL	0120-203-488
Homepage URL
Email	empathy@mebix.co.jp

Sponsor
Institute	Shionogi & Co., Ltd.
Institute
Department

Funding Source
Organization	Shionogi & Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2010 Year 04 Month 15 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2010 Year 04 Month 07 Day
Date of IRB	2010 Year 04 Month 15 Day
Anticipated trial start date	2010 Year 05 Month 01 Day
Last follow-up date	2015 Year 10 Month 31 Day
Date of closure to data entry	2015 Year 11 Month 30 Day
Date trial data considered complete	2016 Year 03 Month 15 Day
Date analysis concluded

Other
Other related information

Management information
Registered date	2010 Year 04 Month 13 Day
Last modified on	2019 Year 07 Month 23 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004199