UMIN-CTR Clinical Trial

Public title

Study of High-dose Olmesartan compared with Telmisartan on Blood pressure and Metabolism in Type 2 Diabetics with Hypertension

Acronym

Study of High-dose Olmesartan compared with Telmisartan on Blood pressure and Metabolism in Type 2 Diabetics with Hypertension

Scientific Title

Study of High-dose Olmesartan compared with Telmisartan on Blood pressure and Metabolism in Type 2 Diabetics with Hypertension

Scientific Title:Acronym

Study of High-dose Olmesartan compared with Telmisartan on Blood pressure and Metabolism in Type 2 Diabetics with Hypertension

Region

Japan

Condition

Type 2 diabetes mellitus with hypertension

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

We compared with effect of telmisartan 80mg/day and olmesartan 40mg/day on blood pressure and metabolic parameters.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

1)decrease of blood pressure
2)achievemenent rate of aim of decreasing blood pressure(<130/80mmHg)

Key secondary outcomes

1)blood pressure of home
2)metabolic parameters(FPG,HbA1c,
FIRI,HOMA-IR,HM-adiponectin)
3)urine albumin
4)inflammatory marker(hs-CRP,IL-6)
5)lipid profiles(TC,TG,HDL-C,LDL-C)

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Institution is not considered as adjustment factor.

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Patients who were being treated with telmisartan 80mg/day at 8 weeks switched to olmesartan. After 12 weeks of olmesartan treatment, we evaluated blood pressure and laboratory data.

Interventions/Control_2

Patients who were being treated with olmesartan 40mg/day at 8 weeks switched to telmisartan. After 12 weeks of telmisartan treatment,we evaluated blood pressure and laboratory data.

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

All patients with type 2 diabetes mellitus with hypertension vistited our Hospital and approved with this study.
They who were being treated with telmisartan 80mg or olumesartan40mg at least for 8 weeks did not reached aim of decrease of blood pressure.
Medication other than antihypertensive drug was not changed for 8weeks.

Key exclusion criteria

1)patients treated with insulin therapy.
2)patients who wrere poorly controlled .
3)patients with secondary hypertension.
4)patients on HD.
5)pregnant patients.
6)patients who wrere allergic to telmisartan and olmesartan.
7)patients with heavy liver dysfunction.
8)patients with heavy renal dysfunction(Cre>3mg/dL).

Target sample size

60

Name of lead principal investigator

1st name	Yosuke
Middle name
Last name	Okada

Organization

University of Occupational and
Environmental Health,Japan

Division name

First Department of Internal Medicine, School of Medicine

Zip code

807-8555

Address

Japan

TEL

093-603-1611

Email

y-okada@med.uoeh-u.ac.jp

Name of contact person

1st name	Tadashi
Middle name
Last name	Arao

Organization

Kyushu Rosai Hospital, Moji Medical Center

Division name

Department of Internal Medicine, Division of Diabetes, Hematology and Collagen Disease

Zip code

801-8502

Address

Japan

TEL

093-331-3461

Homepage URL

Email

t-arao@med.uoeh-u.ac.jp

Institute

University of Occupational and
Environmental Health, Japan

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Ashiya central hospital, Nogata central hospital, Hagiwara central hospital, Kitakyushu city Yahata hospital

Name of secondary funder(s)

Organization

Kyushu Rosai Hospital, Moji Medical Center

Address

3-1 Higashiminatomachi, Moji-ku, Kitakyushu City, Fukuoka

Tel

093-331-3461

Email

t-arao@med.uoeh-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

産業医科大学病院（福岡県）、萩原中央病院（福岡県）、芦屋中央病院（福岡県）、直方中央病院（福岡県）、北九州市立八幡病院（福岡県）

Date of disclosure of the study information

2011

Year

07

Month

31

Day

URL releasing protocol

https://www.jstage.jst.go.jp/browse/endocrj

Publication of results

Published

URL related to results and publications

https://www.jstage.jst.go.jp/browse/endocrj

Number of participants that the trial has enrolled

36

Results

1) The efficacy of decrease of blood pressure showed no difference between olmesartan and telmisartan.
2)On glucose profiles, olmesartan improved FPG,HbA1c,FIRI and HOMA-IR more effectively than telmisartan.
3)Change rate of hs-CRP is correlated with that of HOMA-IR.

Results date posted

2022

Year

08

Month

05

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The age was 68.3years, body weight was 65.0kg, BMI was 25.7kg/m2, and duration of diabetes was 11.7years. Complications were dyslipidemia in 14 patients, cerebrovascular disease in 5 patients, ischemic heart disease in 3 patients, and arteriosclerosis obliterans in 2 patients. Concomitant drugs included antihypertensive agents , antidiabetic agent , and lipid-lowering agents . Table 2 shows the baseline data of study subjects in olmesartan group (A 0W and D 12W) and in telmisartan group (B 12W and C 0W). The body weight was 65.5 versus 65.5kg, BMI was 25.0 versus 25.8kg/m2. The blood pressure was 137.4/73.9 versus 135.6/76.0mmHg, HbA1c was 7.0 versus 6.8 %, FPG was 152.3versus 141.5mg/dL, FIRI was 110.9 versus 11.6 U/mL, HOMA-IR was 3.9versus 3.3, TC was 199.7 versus 193.9mg/dL, HDL-C was 52.6 versus 54.1mg/dL, LDL-C was 122.2 versus 118.0mg/dL, TG was 142.9 versus 128.0mg/dL, hs-CRP was 2424.8 versus 1253mg/mL,and HMW-adiponectin was 7.7versus 7.5g/mL, with no significant difference between the two groups.　

Participant flow

The subjects were male and female outpatients with type 2 diabetes aged over 20 years and under 80 years old (20 men and 16 women) who did not achieve the target of blood pressure <130/80 mmHg following treatment with olmesartan at 40 mg/day or telmisartan at 80 mg/day for 8 weeks or more. The target of blood pressure bases on the guideline for treatment of hypertension of the Japanese Society of Hypertension (JSH 2009). The patients gave consent to participation in this study and their other drugs were not changed for 8 weeks before registration. Exclusion criteria were: 1) diabetic patients on insulin therapy; 2) diabetic patients with unstable glycemic control; 3) secondary hypertension; 4) dialysis; 5) pregnancy or possible pregnancy (in women); 6) a history of hypersensitivity to any of the ingredients of the study drug; 7) serious hepatic disease; 8) serious renal disease (serum creatinine 3 mg/dL); and 9) any other reason judged by the attending physician to make the patient inappropriate for the study. The hospital ethics committee approved this protocol, and informed consent was obtained from each subject.
The primary endpoint (blood pressure reduction rate) and the secondary endpoints [body weight (BMI), parameters of glucose metabolism [HbA1c (NGSP), FPG, FIRI, HOMA-IR and HMW-adiponectin], inflammatory marker (hs-CRP), and serum lipids (TC, LDL-C, HDL-C, and TG)] were measured in Weeks 0, 12, and 24. Drugs were switched in Week 12 to investigate the changes that occurred. Olmesartan group (n=36) show A (n=19) and D (n=17), and telmisartan group (n=36) indicate B (n=19) and C (n=17).　
The BP measurement was made three times by doctors using sphygmomanometers in the sitting position for outpatients, and we used the average of those.
Concomitant drugs were not changed to non-specified drugs during the study (the observation and treatment periods). All adverse events (subjective and objective symptoms and abnormal laboratory data), including dizziness, hypotension, and hepatic dysfunction, that were encountered during the study period were investigated to determine their nature, timing of remission, severity, actions taken, outcome, seriousness, and causal relation with the study drug. This information was recorded in the medical charts. Follow up was performed when necessary.

Adverse events

None.

Outcome measures

The blood pressure in olmesartan group (A 12W and D 24W) and in telmisartan group (B 24W and C 12W) was respectively 135.0/73.9 versus 135.0/74.2 mmHg, and the percent decrease of blood pressure was -1.5/0.8 versus -0.0/-1.5, with no significant difference between the two groups. HbA1c was 6.9 in olmesartan group (A 12W and D 24W) versus 7.0in telmisartan group (B 24W and C 12W), FPG was 144.0 versus 147.9 mg/dL, FIRI was 12.1 versus 10.5, and HOMA-IR was 3.3 versus 3.7, and there were no change in measured data. The percent change of HbA1c, FPG, FIRI, HOMA-IR was -2.2versus 3.8 (p=0.0013), -4.2 versus 5.6(p=0.0066), 4.6 versus 10.5, and -1.2 versus 25.3(p=0.0423), respectively, and there was significant improvement of glycemic control and insulin resistance (IR) in olmesartan group.
TC was 197.4 in olmesartan group versus 194.8mg/dL in telmisartan group, HDL-C was 55.5 versus 52.0 mg/dL, LDL-C was 118.6 versus 117.6 mg/dL, and TG was 131.8 versus 140.2mg/dL. The percent change of TC was -0.2 versus 1.6, while it was 6.0 versus -2.8 (p=0.0174) for HDL-C -0.5 versus -0.1 for LDL-C, and 3.8 versus 16.1 for TG. HDL-C increased significantly in olmesartan group both in terms of the absolute value (p=0.0237) and percent change (p=0.0174).
The hs-CRP level was 1162.1 in olmesartan group versus 1609.6mg/mL in telmisartan group and its percent change was 23.3 versus 112.9, with a decrease being seen in olmesartan group. There was difference of HMW-adiponectin levels (8.8 versus 8.0), and a significant increase (p=0.0219) was seen in olmesartan group, but the percent change was not different (8.2 versus 4.1). There were no differences of body weight (BMI) in terms of both the absolute value and the percent change. A positive correlation was observed between the percent change of HOMA-IR and hs-CRP in olmesartan group (r=0.39, p<0.05) .

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2009

Year

05

Month

19

Day

Date of IRB

2009

Year

05

Month

21

Day

Anticipated trial start date

2009

Year

06

Month

01

Day

Last follow-up date

2011

Year

06

Month

01

Day

Date of closure to data entry

2011

Year

06

Month

01

Day

Date trial data considered complete

2011

Year

06

Month

01

Day

Date analysis concluded

2011

Year

06

Month

01

Day

Other related information

Olmesartan was more beneficial than telmisartan for improving
glucose profiles than telmisartan.
Considering of correlation with change rate of hs-CRP and HOMA-IR, it suggests that mechanism of improving glucose profiles of olmesartan is associated with anti-inflammatory effect besides strong inhibition of RAS.

Registered date

2011

Year

07

Month

26

Day

Last modified on

2022

Year

08

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006834