UMIN-CTR Clinical Trial

Public title

Japanese evaluation between FormuLa of Azelnidipine and amlodipine
add on olmesartan to Get antialbuminuric effect study

Acronym

Japanese evaluation between FormuLa of Azelnidipine and amlodipine
add on olmesartan to Get antialbuminuric effect study (J-FLAG)

Scientific Title

Japanese evaluation between FormuLa of Azelnidipine and amlodipine
add on olmesartan to Get antialbuminuric effect study

Scientific Title:Acronym

Japanese evaluation between FormuLa of Azelnidipine and amlodipine
add on olmesartan to Get antialbuminuric effect study (J-FLAG)

Region

Japan

Condition

Hypertensive patients with albuminuria and diabetes (diabetic nephropathy)

Classification by specialty

Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To compare antialbuminuric effect between azelnidipine (8 to 16 mg/day) and amlodipine (2.5 to 5 mg/day) in combination with olmesartan

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Not applicable

Primary outcomes

Changes in urinary albumin/creatinine (Cr) ratio in spot urine from pretreatment period (average of 2 measured value) to 12 months of treatment

Key secondary outcomes

1. Percent changes in urinary albumin/Cr ratio from pretreatment period to each period of treatment. Urinary protein/Cr ratio is analyzed similarly to urinary albumin/Cr ratio.
2. Urinary liver-type free fatty acid-binding protein (L-FABP)
3. Urinary 8-hydroxydeoxyguanosine (8-OHdG)
4. Office blood pressure (BP) in outpatient clinic
5. Pulse rate
6. Serum Cr or estimated glomerular filtration rate (eGFR) calculated using the modified MDRD formula in the Japanese Society of Nephrology: eGFR (ml/min/1.73 m2) = 194 x age -0.287 x serum creatinine – 1.094 (multiply by 0.739 in female)
7. Cerebro-cardio-vascular events: cerebro-cardio-vascular mortality (fatal myocardial infarction, fatal heart failure, sudden death, fatal stroke, other cardiovascular death) and hospitalization due to cerebro-cardio-vascular disease (nonfatal myocardial infarction, angina, heart failure, cerebral bleeding, cerebral infarction, transient cerebral ischemic attack)

Study type

Interventional

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

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Azelnidipine (8 to 16 mg/day) is added in patients with olmesartan and target blood pressure (BP) is under 130/80 mmHg,

Interventions/Control_2

Amlodipine (2.5 to 5 mg/day) is added in patients with olmesartan and target BP is under 130/80 mmHg

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>

Gender

Male and Female

Key inclusion criteria

Patients fulfilled all the condition of the following in pretreatment period can participate
1. Outpatient systolic BP is >=130 mmHg and <180 mmHg, and/or outpatient diastolic BP is >=80 mmHg and <110 mmHg
2. Urinary albumin/Cr >=30 mg/g in spot urine
3. Fasting blood sugar >=126 mg/dL or treatment with antidiabetic agents
4. Serum Cr <=2.0 mg/dL
5. Age is >=20 and <80 year-old
6. Olmesartan (10 to 20 mg/day) is administered for more than 1 month and calcium channel blocker (CCB) is not given or more than 1 month.
7. Written informed consent is obtained based on written and oral explanation of physician in charge

Key exclusion criteria

Patients who apply any of the flowing cannot participate
1. Hypertensive emergency that requires intravenous administration of antihypertensives
2. Nephritic syndrome (urinary protein >=3.5 g/day and serum total protein <=6.0 g/dL [or serum albumin <=3.0 g/dL])
3. Adminstration of contraindication drugs (angiotensin converting enzyme [ACE] inhibitor, angiotensin receptor blocker [ARB] other than olmesartan, CCB other than the assigned one, adrenocorticosteriod, immunosuppressant, azole antifungal agent [itraconazole, miconazole, etc.], HIV protease inhibitor [ritonavir, saquinqvir, indinavir, etc]) or long-term (>= 2 weeks) administration of non-steriod anti-inflammatory drugs (NSAID)
4. Past history of severe side effect of CCB, ARB, or ACE inhibitor
5. Cerebrovascular disease occurs within 6 months
6. Sever heart failure (NYHA class >= III), severe arrhythmia (frequent ventricular or atrial extrasystole, prolonged ventricular tachycardia, atrial tachyrhythmia with severe tachycardia, atrial fibrillation or flutter with severe tachycardia, sick sinus syndrome with severe bradycardia, atrio-ventricular block with severe bradycardia), myocardial infarction or percutaneous transluminal coronary angioplasty within 6 months
7. Type 1 diabetes and type 2 diabetes required hospitalization due to high hemoglobin A1c (>= 9.0), extremely high blood glucose, or diabetic ketoacidosis
8. AST or ALT is more than 5 times higher upper limits
9. Malignancy
10. Pregnant, possible to be pregnant, or willing to be pregnant
11. Patients who are inadequate by determination of physician in charge

Target sample size

250

Name of lead principal investigator

1st name
Middle name
Last name	Toshiro Fujita

Organization

University of Tokyo Graduate School of Medicine

Division name

Department of Nephrology and Endocrinology

Zip code

Address

7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8165, Japan

TEL

03-5800-9735

Email

Name of contact person

1st name
Middle name
Last name	Katsuyuki Ando

Organization

University of Tokyo Graduate School of Medicine

Division name

Division of Molecular Cardiovascular Metabolism

Zip code

Address

7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8165, Japan

TEL

03-5800-9119

Homepage URL

Email

katsua-tky@umin.sc.jp

Institute

J-FLAG Study Group

Institute

Department

Personal name

Organization

The Waksman Foundation of Japan Inc.

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2009

Year

01

Month

29

Day

URL releasing protocol

Publication of results

Unpublished

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

Recruitment status

Completed

Date of protocol fixation

2008

Year

11

Month

20

Day

Date of IRB

Anticipated trial start date

2009

Year

05

Month

01

Day

Last follow-up date

2011

Year

12

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2009

Year

01

Month

29

Day

Last modified on

2012

Year

04

Month

24

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001971