UMIN-CTR Clinical Trial

Public title

COmbination Strategy on renal function of the benidipine or diuretics treatMent with RAS inhibitOrs in CKD hypertensive population

Acronym

COmbination Strategy on renal function of the benidipine or diuretics treatMent with RAS inhibitOrs in CKD hypertensive population (COSMO-CKD)

Scientific Title

COmbination Strategy on renal function of the benidipine or diuretics treatMent with RAS inhibitOrs in CKD hypertensive population

Scientific Title:Acronym

COmbination Strategy on renal function of the benidipine or diuretics treatMent with RAS inhibitOrs in CKD hypertensive population (COSMO-CKD)

Region

Japan

Condition

Hypertensive patients with albuminuria under the treatment of the inhibitor of the renin-angiotension system (RAS)

Classification by specialty

Medicine in general

Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To compare the antialbuminuric effect between L/T-type calcium channel blocker (CCB) benidipine (4 to 8 mg/day) and thiazide diuretic hydrochlorthiazide (6.25 to 12.5 mg/day) as addition of RAS inhibitor in hypertensive patients with CKD

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. Urinary albumin/Cr ratio in fspot urine: Percent changes from pretreatment period to each period of treatment, etc.
2. 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 Cr - 1.094 (multiply by 0.739 in female)
3. Urinary liver-type free fatty acid-binding protein (L-FABP)
4. Serum Cr
5. Blood urea nitrogen (BUN)
6. Office blood pressure (BP)
7. Pulse rate
8. Renal events: Start of dialysis, renal transplantation
9. Cerebro-cardio-vascular events: Cerebro-cardio-vascular death (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

Benidipine (4 to 8 mg/day) is added in patients with the treatment of the RAS inhibitor.
If BP does not reach to lower than 130/80 mmHg, other antihypertensive drug than CCB, diuretic and RAS inhibitor is added.

Interventions/Control_2

Hydrochlorthiazide (6.25 to 12.5 mg/day) is added in patients with the treatment of the RAS inhibitor.
If BP does not reach to lower than 130/80 mmHg, other antihypertensive drug than CCB, diuretic and RAS inhibitor is added.

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 to fulfill all the following condition at the start of the study can participate
1. Outpatient systolic BP is equal or more than130 mmHg and/or outpatient diastolic BP is equal or more than 80 mmHg.
2. Urinary albumin/Cr ratio at pretreatment period (average of 2 measured value) is equal or more than 300 mg/g
3. eGFR is equal or more than 30 mL/min/1.73m2.
4. Age is equal or more than 20 and less than 80 year-old
5. RAS inhibitor has been administered for more than 3 months and CCB and diuretic heve not been given within 3 months
6. 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 condition cannot participate
1. Outpatient systolic BP is equal or more than 180 mmHg and/or outpatient diastolic BP is equal or more than 110 mmHg. Or hypertensive emergency that requires intravenous administration of antihypertensives
2. Administration of adrenocorticosteroidal drug, immunosuppressant or long-term (equal or more than 2 weeks) administration of non-steroid anti-inflammatory drugs (NSAID)
3. Past history of severe side effect of CCB, thiazide diretic, ARB or ACE inhibitor
4. Type 1 diabetes and type 2 diabetes required hospitalization due to high hemoglobin A1c (equal and more than 9.0%), extremely high blood glucose, or diabetic ketoacidosis
5. Cerebrovascular disease occurs within 6 months
6. Sever heart failure (NYHA class is equal or more than 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), angina, or myocardial infarction within 6 months
7. AST or ALT is more than 5 times higher upper limits
8. Pregnant, possible to be pregnant, or willing to be pregnant
9. Patients who are inadequate by determination of physician in charge

Target sample size

400

Name of lead principal investigator

1st name
Middle name
Last name	Toshiro Fujita

Organization

University of Tokyo Graduste School of Medicine

Division name

Department of Nephrology and Endocrinology

Zip code

Address

7-3-1 Hongo,Bunkyo-ku,Tokyo 113-8655, Japan

TEL

Email

Name of contact person

1st name
Middle name
Last name	Katsuyuki Ando

Organization

University of Tokyo Graduste School of Medicine

Division name

Division of Molecular Cardiovascular Metabolism

Zip code

Address

7-3-1 Hongo,Bunkyo-ku,Tokyo 113-8655Japan

TEL

03-5800-9119

Homepage URL

Email

Katsua-tky@umin.sc.jp

Institute

COSMO-CKD Study Group

Institute

Department

Personal name

Organization

The Kidney 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

07

Month

01

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

Enrolling by invitation

Date of protocol fixation

2009

Year

03

Month

26

Day

Date of IRB

Anticipated trial start date

2009

Year

07

Month

01

Day

Last follow-up date

2013

Year

03

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2009

Year

06

Month

30

Day

Last modified on

2011

Year

06

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002564