UMIN-CTR Clinical Trial

Public title

Comparisons of Oral Agents to Standardize Treatment
for diabetes in Japan

Acronym

COAST-J

Scientific Title

Comparisons of Oral Agents to Standardize Treatment
for diabetes in Japan

Scientific Title:Acronym

COAST-J

Region

Japan

Condition

Type 2 diabetes

Classification by specialty

Medicine in general

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Direct comparisons of efficacy and durability of metformin and DPP-4 inhibitors in the treatment of patients with type 2 diabetes in Japan

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

1) The proportion of participants with HbA1c levels less than 7.0 % at the 52nd week with the Stage One treatment.
2) The proportion of participants with HbA1c levels less than 7.0 % at the 78th,104th,130th, and 156th week with the Stage One treatment.

Key secondary outcomes

1) The proportion of participants with HbA1c levels less than 6.2 % at the 52nd week with the Stage One treatment.
2) The tolerance rate for preselected "therapeutic" dose of the drug for intervention.
3) Percent point change in the HbA1c levels form baseline to post-intervention (at the 4th, 8th, 12th, 24th, 36th, and 52nd week).
4) Values of and change in fasting plasma glucose, body weight, blood pressure, and serum cholesterol , HDL cholesterol, and triglyceride at the 0, 4th, 8th, 12th, 24th, 36th, and 52nd week.
5) Values of and change in serum 1,5-anhydroglucitol at the 0, 4th, 8th, 12th, 24th, and 52nd week.
6) Values of and change in serum glycoalbumin at the 0, 4th, 8th, 12th, 24th week.
7) The proinsulin:insulin ratio, HOMA2-IR, and HOMA2-B before and after 52 weeks after the beginning of the treatment.
8) Values of and change in urine albumin:creatinine ratio at 0, 12th, 24th, 36th, and 52nd week.
9)The proportion of participants who fullfilled the criteria of Stage One treatment, Stage Two treatment, and dropout.
10) The difference between the baseline characteristics and labolatory data of the participants whose HbA1c levels are and are not less than 7% at the 52nd week with the drug of intervention.
11)The proportion of participants with HbA1c levels less than 6.2 % at the 78th,104th,130th, and 156th week with the Stage One treatment.
12) Percent point change in the HbA1c levels from baseline to the 78th, 104th, 130th, and 156th week.
13) Values of and change in fasting plasma glucose level and body weight at the 0, 65th, 78th, 91st, 104th, 117th, 130th, and 156th week.
14)HOMA2-IR, and HOMA2-B at the 104th and 156th week.
15) The adherence of the drug of intervention.
16) The proportion of participants who deviated from the protocol.
17) Safety and adverse events.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

1) To take 250 to 2250 mg/day (twice or three times a day) of metformin hydrochloride for 52 weeks. Up to the same dose of glimepiride or gliclazide as in the screening period can be used additionally (Stage One treatment).
2) If participants fail to keep the value of HbA1c less than 8.0 % by Stage One treatment, glimepiride (up to 6 mg) is used additionally with metformin hydrochloride until the 52th week (Stage Two treatment).
3) If participants maintain the value of HbA1c less than 7.0 % after the 52th week, Stage One treatment is continued until the 156th week. Stage One treatment is discontinued when HbA1c level reaches 8.0%.

Interventions/Control_2

1) To take one of the DPP-4 inhibitors for 52 weeks. Up to the same dose of glimepiride or gliclazide as in the screening period can be used additionally (Stage One treatment).
2) If participants fail to keep the value of HbA1c less than 8.0 % by Stage One treatment, glimepiride (up to 6 mg) is used additionally with one of the DPP-4 inhibitors until the 52th week (Stage Two treatment).
3) If participants maintain the value of HbA1c less than 7.0 % after the 52th week, Stage One treatment is continued until the 156th week. Stage One treatment is discontinued when HbA1c level reaches 8.0%.

Interventions/Control_3

1) To continue the therapy for diabetes mellitus during the screening period. Up to the same dose of glimepiride or gliclazide as in the screening period can be used (Stage One treatment).
2) If participants fail to keep the value of HbA1c less than 8.0 % by Stage One treatment, glimepiride (up to 6 mg) is used additionally with Stage One treatment until the 52th week (Stage Two treatment).
3) If Stage One treatment maintain the value of HbA1c less than 7.0 % after the 52th week, Stage One treatment is continued until the 156th week. Stage One treatment is discontinued when HbA1c level reaches 8.0%.

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

72

years-old

>

Gender

Male and Female

Key inclusion criteria

1. Diagnosis of type 2 diabetes mellitus by the criteria of Japan Diabetes Society.
2. If female, not currently pregnant or not planning pregnancy during the study period.
3. Body mass index less than 30 kg/m2.
4. Diabetes is treated with any of the following therapies with three month prior to study enrollment: (1) medical nutrition therapy alone; (2) monotherapy with the same dose of glimepiride (=< 4mg per day); (3) monotherapy with the same dose of gliclazide (=< 80mg per day).
5. 7% =< HbA1c < 9%.
6. Stable HbA1c (difference between the HbA1c of the latest visit (21 days to three months before the screening visit) and that of the screening visit is less than or equal to 1.0% points).
7. Stable HbA1c (difference between the HbA1c of all the visits (within 20 days before the screening visit, if any) and that of the screening visit are less than or equal to 1.0% points)
8. Subject has given full written informed consent prior to the study.

Key exclusion criteria

1. Pregnancy or lactation.
2. Previous adverse effects on either metformin or DPP-4 inhibitors.
3. a)GADA positivity, history of lactic acidosis, or severe complication derived from diabetes or other diseases, b)history of diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, or massive ketonuria within 6 months prior to screening visit.
4. Episode of severe infection, massive hemorrhage or donation of blood within 4 weeks prior to screening visit.
5. Administeration glucocorticoids or immunosuppressive medications.
6. Renal insufficiency (value of serum creatinine equal to or above 1.3mg/dL in man or equal to or above 1.2mg/dL in women or eGFR less than 40).
7. Abnormal liver function (value of AST and/or ALT more than the double of the normal upper limit) or liver cirrosis.
8.Presence of edema.
9.Heart failure.
10.Respiratory failure.
11.Alcohol abuse.
12.Hematological diseases including anemia (Hb value less than 11g/dL in men and less than 10g/dL in women).
13.Likely to be non-compliant, in the investigator's opinion, with respect to the protocol and related scheduled visits.
14.Any clinical condition or significant concurrent disease judged by the investigator to complicate the evaluation of the study treatment.

Target sample size

1326

Name of lead principal investigator

1st name
Middle name
Last name	Mitsuhiko Noda

Organization

National Center for Global Health and Medicine

Division name

Department of Diabetes and Metabolic Medicine

Zip code

Address

1-21-1 Toyama, Shinjuku-ku, Tokyo, Japan

TEL

03-5273-6955

Email

dm-ing5@hosp.ncgm.go.jp

Name of contact person

1st name
Middle name
Last name	Ritsuko Yamamoto-Honda

Organization

National Center for Global Health and Medicine

Division name

Department of Diabetes and Metabolic Medicine

Zip code

Address

1-21-1 Toyama, Shinjuku-ku, Tokyo, Japan

TEL

03-5273-6955

Homepage URL

http://ncgm-dm.jp/coast-j/index.html

Email

dm-ing5@hosp.ncgm.go.jp

Institute

Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine

Institute

Department

Personal name

Organization

Japan Foundation for the Promotion of International Medical Research Cooperation (until 31/March/2013)

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

独立行政法人国立国際医療研究センター病院（東京都）、独立行政法人国立国際医療研究センター国府台病院（千葉県）、信州大学大学附属病院（長野県）、徳島大学病院（徳島県）、国家公務員共済組合連合会 虎の門病院（東京都）、JR東京総合病院（東京都）、社会福祉法人 三井記念病院（東京都）、日本赤十字社大森赤十字病院（東京都）、岐阜大学医学部附属病院（岐阜県）、笹塚井上クリニック（東京都）、社会保険中央病院（東京都）、東京都保健医療公社 多摩北部医療センター（東京都）、医療法人社団 六医会インペリアルタワー診療所（東京都）、医療法人康麗会 笛吹中央病院（山梨県）、医療法人 慈誠会 山根病院（島根県）、福島県立医科大学附属病院（福島県）、名古屋大学医学部附属病院老年内科（愛知県）、香川県立中央病院（香川県）、福山市民病院（広島県）、飯塚市立病院（福岡県）、やごうクリニック（東京都）、国家公務員共済組合連合会 三宿病院（東京都）、山本診療所（福岡県）、下奥多摩医院（東京都）、小山イーストクリニック（栃木県）

Date of disclosure of the study information

2011

Year

03

Month

28

Day

URL releasing protocol

http://ncgm-dm.jp/coast-j/index.html

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

No longer recruiting

Date of protocol fixation

2011

Year

03

Month

17

Day

Date of IRB

Anticipated trial start date

2011

Year

03

Month

18

Day

Last follow-up date

2016

Year

03

Month

31

Day

Date of closure to data entry

2016

Year

06

Month

30

Day

Date trial data considered complete

2016

Year

07

Month

31

Day

Date analysis concluded

2017

Year

12

Month

01

Day

Other related information

Registered date

2011

Year

03

Month

28

Day

Last modified on

2016

Year

07

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006064