UMIN-CTR Clinical Trial

Basic information
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
Condition	Type 2 diabetes mellitus with hypertension
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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)

Base
Study type	Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute	University of Occupational and Environmental Health, Japan
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Ashiya central hospital, Nogata central hospital, Hagiwara central hospital, Kitakyushu city Yahata hospital
Name of secondary funder(s)

IRB Contact (For public release)
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
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
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）

Other administrative information
Date of disclosure of the study information	2011 Year 07 Month 31 Day

Related information
URL releasing protocol	https://www.jstage.jst.go.jp/browse/endocrj
Publication of results	Published

Result
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

Progress
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
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.

Management information
Registered date	2011 Year 07 Month 26 Day
Last modified on	2022 Year 08 Month 05 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000006834