UMIN-CTR Clinical Trial

Public title

Renoprotective effects of azelnidipine in hypertensive diabetic patients in Mie

Acronym

RANDAM

Scientific Title

Renoprotective effects of azelnidipine in hypertensive diabetic patients in Mie

Scientific Title:Acronym

RANDAM

Region

Japan

Condition

essential hypertension with type 2 diabetes mellitus and albuminuria

Classification by specialty

Cardiology	Endocrinology and Metabolism	Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Albuminuria is a powerful prognostic predictor of cardiovascular disease in patients with hypertension and diabetes. Several guidelines for the management of hypertension recommend aggressive blood pressure reduction as well as the use of inhibitors of the renin-angiotensin system to slow the decline of kidney function in patients with albuminuria. Most of such patients require a combination of a renin-angiotensin system blocker with either a calcium channel blocker or diuretic to achieve blood pressure goal. Although the GUARD study demonstrated that treatment using an angiotensin converting enzyme inhibitor with a diuretic resulted in a greater reduction in albuminuria compared to the group of angiotensin converting enzyme inhibitor and a calcium channel blocker, amlodipine, some calcium channel blockers, such as azelnidipine, have been reported to exert renoprotective effects. Thus, the present study was designed to test the hypothesis that combining an angiotensin receptor blocker with either a calcium channel blocker, azelnidipine, or a thiazide diuretic will cause similar reductions in blood pressure and albuminuria in patients with hypertension and diabetes mellitus.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Primary endpoint is the change in the ratio of urine albumin to creatinine (Alb/Cr) from baseline to week 24.

Key secondary outcomes

(1) The change in the urine Alb/Cr ratio from baseline to week 12.
(2) The change in estimated glomerular filtration ratio from baseline to week 12 and 24.
(3) Proportion of patients who progress to overt diabetic nephropathy
(4) The magnitude of albuminuria
(5) The changes in serum creatinine, potassium, sodium, LDL-cholesterol, HDL-cholesterol, and HbA1c levels
(6) The changes in urine excretion of sodium
(7) The changes in clinic blood pressure and heart rate
(8) The changes in self-measured blood pressure at home

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

RANDAM is a 24-week, prospective, randomized, open, blinded-endpoint (PROBE) study. After a screening phase for eligibility, inhibitors of the renin-angiotensin system, calcium channel blockers, and diuretics are withdrawn. This was followed by a 12-week run-in period where patients are treated with a combination of olmesartan 20mg/day and amlodipine 5mg/day. At the end of the run-in period, baseline data are obtained. Then, amlodipine is withdrawn and patients are assigned to receive azelnidipine 16mg/day in combination with olmesartan 20mg/day for another 24-week (randomization). Antihypertensive drugs other than inhibitors of the renin-angiotensin system, calcium channel blockers, and diuretics are allowed throughout the study period and upward-titration of such medication (alpha-blockers or beta-blockers) is implemented to reach a target clinic blood pressure of <130/80mmHg. Data are obtained at 12- and 24-week. The target of glycemic levels is HbA1c of less than 6.5%. The addition of a thiazolidinedione is not allowed during the study period.

Interventions/Control_2

After a screening phase for eligibility, inhibitors of the renin-angiotensin system, calcium channel blockers, and diuretics are withdrawn. This was followed by a 12-week run-in period where patients are treated with a combination of olmesartan 20mg/day and amlodipine 5mg/day. At the end of the run-in period, baseline data are obtained. Then, amlodipine is withdrawn and patients are assigned to receive trichlorthiazide 1mg/day in combination with olmesartan 20mg/day for another 24-week (randomization). Antihypertensive drugs other than inhibitors of the renin-angiotensin system, calcium channel blockers, and diuretics are allowed throughout the study period and upward-titration of such medication (alpha-blockers or beta-blockers) is implemented to reach a target clinic blood pressure of <130/80mmHg. Data are obtained at 12- and 24-week. The target of glycemic levels is HbA1c of less than 6.5%. The addition of a thiazolidinedione is not allowed during the study period.

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

75

years-old

>=

Gender

Male and Female

Key inclusion criteria

Hypertensive patients with type 2 diabetes mellitus and albuminuria (30-600mg/g creatinine) with clinic blood pressure >130/80mmHg under a monotherapy with a standard dosage of an inhibitor of the renin-angiotensin system.

Key exclusion criteria

Exclusion criteria are: secondary hypertension; history of acute coronary syndrome, heart failure, coronary revascularization, or stroke within the previous 6 months; uncontrolled diabetes mellitus (HbA1c >9.0%); a disorder that requires treatment with calcium channel blockers or diuretics; confirmed or suspected renal artery stenosis; serum creatinine of 2.0mg/dl or more for men and 1.5mg/dl or more for women; pregnant women; or clinic systolic blood pressure >180mmHg and/or diastolic blood pressure >110mmHg.

Target sample size

146

Name of lead principal investigator

1st name
Middle name
Last name	Masayoshi Kojima

Organization

Komono Kosei Hospital

Division name

Department of Internal Mediine

Zip code

Address

75 Fukumura, Komono-cho, Mie

TEL

Email

Name of contact person

1st name
Middle name
Last name

Organization

Komono Kosei Hospital

Division name

Department of Internal Medicine

Zip code

Address

m-kojima@kkh.miekosei.or.jp

TEL

Homepage URL

Email

m-kojima@kkh.miekosei.or.jp

Institute

Komono Kosei Hospital

Institute

Department

Personal name

Organization

none

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

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

菰野厚生病院（三重県）
いなべ総合病院（三重県）
カトウ医院（三重県）
三重県立総合医療センター（三重県）
坂井橋クリニック（三重県）
主体会病院（三重県）
市立四日市病院（三重県）
武内病院（三重県）
村瀬病院（三重県）
山本総合病院（三重県）
あのつクリニック（三重県）
池田内科循環器科（三重県）
坂倉内科（三重県）
永井病院（三重県）
みやがわクリニック（三重県）
山の手クリニック（三重県）
らんクリニック（三重県）

Date of disclosure of the study information

2010

Year

04

Month

06

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

2009

Year

09

Month

01

Day

Date of IRB

Anticipated trial start date

2010

Year

02

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2010

Year

04

Month

05

Day

Last modified on

2012

Year

04

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004153