UMIN-CTR Clinical Trial

Public title

Investigation on the effectiveness and safety of lipid-lowering treatments in patients with familial hypercholesterolemia (FAME: Familial Hypercholesterolemia Expert Forum Trial)

Acronym

Familial Hypercholesterolemia Expert Forum Trial (FAME)

Scientific Title

Investigation on the effectiveness and safety of lipid-lowering treatments in patients with familial hypercholesterolemia (FAME: Familial Hypercholesterolemia Expert Forum Trial)

Scientific Title:Acronym

Familial Hypercholesterolemia Expert Forum Trial (FAME)

Region

Japan

Condition

familial hypercholesterolemia

Classification by specialty

Medicine in general

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the effectiveness and safety of long-term lipid-lowering treatments by statins, ezetimibe and other hypolipidemic drugs in patients with familial hypercholesterolemia

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

Effectiveness (lowering effects on serum lipids and intima-media thickness of the carotid arteries) and safety of lipid-lowering drugs

Key secondary outcomes

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

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

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Inclusion criteria for patients with familial hypercholesterolemia: All of the following 4 criteria must be met.
1) Patients who are diagnosed as heterozygous familial hypercholesterolemia (FH) assessed by the clinical diagnostic criteria settled by the Research Committee of the Japanese Ministry of Health, Labour and Welfare. Patients with scores > 8 are definite FH and those with scores with 6 or 7 are probable FH.
2) Patients should have their serum LDL cholesterol level >100 mg/dl. If patients have been taking ezetimibe, the pre-treatment level of LDL cholesterol should be >100 mg/dl.
3) Study subjects should be outpatients of hospitals which participate in this study.
4) Patients who gave a written informed consent. If patients are under 16 years old, a written informed consent should be taken from their legally authorized representatives. If patients are 16 to 19 years old, a written informed consent should be taken from both patients and their legally authorized representatives.

Key exclusion criteria

1) Patients whose serum triglyceride level is over 400 mg/dl at the time of registration should be excluded.
2) Patients who are suffering from severe liver dysfunction (acute phase and decompensated cirrhosis)
3) Patients with dyslipidemia who are suffering from the following diseases (1) hypothyroidism (2) pancreatitis
4) Patients with uncontrolled diabetes mellitus, whose HbA1c level is over 9%.
5) Patients who are pregnant, suckling or likely to be pregnant.
6) Patients who are judged by the doctor to be improper to be enrolled in this study.

Target sample size

1000

Name of lead principal investigator

1st name	Shizuya
Middle name
Last name	Yamashita

Organization

Osaka University Graduate School of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

565-0871

Address

Yamadaoka 2-2, Suita, Osaka, Japan

TEL

06-6879-3633

Email

shizu@cardiology.med.osaka-u.ac.jp

Name of contact person

1st name	Daisaku
Middle name
Last name	Masuda

Organization

Osaka University Graduate School of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

565-0871

Address

Yamadaoka 2-2, Suita, Osaka, Japan

TEL

06-6879-3633

Homepage URL

Email

masuda@cardiology.med.osaka-u.ac.jp

Institute

Osaka University Graduate School of Medicine

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

Osaka University Hospitaal

Address

Yamadaoka 2-2, Suita, Osaka, Japan

Tel

06-6879-5685

Email

rinri@hp-crc.med.osaka-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

千葉大学大学院 医学研究院 臨床遺伝子応用医学（千葉県）
日本医科大学　内科学内分泌代謝部門（東京都）
自治医科大学　内科学講座　内分泌代謝学部門（栃木県）
京都大学大学院医学研究科　人間健康科学系専攻 （京都府）
大阪大学医学部附属病院　循環器内科（大阪府）
国立循環器病センター研究所　バイオサイエンス部免疫応答研究室（大阪府）
医療法人天神会新古賀病院（福岡県）
弘前大学大学院　医学研究科　内分泌代謝内科学講座（青森県）
山形大学医学部　臨床検査医学（山形県）
東北大学大学院医学系研究科分子代謝病態学（宮城県）
医療法人松田会鶴ｹ谷クリニック（宮城県）
公立大学法人福島県立医科大学医学部 内科学第三講座 （福島県）
筑波大学大学院　内分泌代謝・糖尿病内科 （茨城県）
防衛医科大学校内科学講座老年内科（埼玉県）
国保松戸市立病院　健康管理室（千葉県）
東邦大学医療センター佐倉病院（千葉県）
東京大学大学院　医学系研究科 糖尿病・代謝内科 （東京都）
自治医科大学　内分泌代謝科（栃木県）
順天堂大学医学部　循環器内科学（東京都）
順天堂大学医学部　循環器内科学（東京都）
順天堂大学医学部　臨床検査医学講座（東京都）
日本大学医学部 小児科分野 （東京都）
東邦大学医学部内科学　糖尿病・代謝・内分泌センター（東京都）
昭和大学医学部　内科学講座　糖尿病・代謝・内分泌内科部門（東京都）
慶應義塾大学医学部 老年内科（東京都）
帝京大学医学部 内科学講座 （東京都）
杏林大学医学部　高齢医学（東京都）
中谷内科クリニック（東京都）
名古屋市立大学大学院医学研究科 生物化学 （愛知県）
名古屋大学医学部附属病院　老年科（愛知県）
金沢医科大学循環制御学（石川県）
福井大学医学部附属病院　第三内科（福井県）
京都大学医学部附属病院 探索医療センター探索医療臨床部 （京都府）
大阪市立大学大学院医学研究科 代謝内分泌病態内科学（大阪府）
大阪中央病院　循環器科（大阪府）
医療法人社団飛翔会寛田クリニック（広島県）
医療法人たかまき会　山崎病院（広島県）
日本大学医学部 内科学系　循環器内科学分野（東京都）
山口大学医学部附属病院　臨床試験支援センター（山口県）

Date of disclosure of the study information

2010

Year

02

Month

19

Day

URL releasing protocol

https://www.jstage.jst.go.jp/browse/jat/-char/ja/

Publication of results

Published

URL related to results and publications

https://www.jstage.jst.go.jp/browse/jat/-char/ja/

Number of participants that the trial has enrolled

769

Results

762 heterozygous and 7 homozygous FH patients were enrolled. CAD was recorded in 23% of patients. Patients without CAD with LDL-C < 100mg/dL, 12.3% and those with CAD with < 70 mg/dL, 1.8%. Male gender, age > 40, FH score < 20, hypertension, and sibling CAD were significantly positively associated with CAD. Male gender, CAD at the baseline, and parental CAD were related to the development of atherosclerotic cardiovascular disease events.

Results date posted

2021

Year

03

Month

02

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Xanthoma or thickening of Achilles tendon was observed in more than 80% of patients. CAD was recorded in 23% of patients. Patients with parental and sibling CAD accounted for 47% and 24%, respectively. At baseline, patients without CAD who had LDL-C <100 mg/dL accounted for 12.3% and those with CAD who had attained the target (LDL-C <70 mg/dL) in the secondary prevention accounted for only 1.8%. In the multiple logistic analysis, male gender, age>40, heterozygous FH score >20, hypertension, and sibling CAD were significantly positively associated with prevalent CAD while serum HDL-cholesterol showed a significant inverse association with CAD. Patients treated with statin alone, statin + ezetimibe, statin + resin, or statin + probucol were 31.1%, 26.3%, 4.0%, and 3.7%, respectively. Patients treated with three-drug combination (statin + ezetimibe + resin or statin + ezetimibe + probucol) accounted for 7.5%. Statins were used in 88.0% of patients, and ezetimibe in 48.0% of patients at the baseline. Although high-intensity statins were mainly prescribed, the doses of statins were much smaller than those reported in the western countries.

Participant flow

The FAME Study enrolled 762 heterozygous (including 17 newly diagnosed cases) and 7 homozygous FH patients from hospitals and clinics nationwide. Diagnosis of FH was based upon the criteria defined in the Study Report in 2008 of Research Committee on Primary Hyperlipidemia supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare.

Adverse events

There was no concern regarding the long-term safety of lipid-lowering drugs.

Outcome measures

CAD was diagnosed in 17 patients with 21 episodes during follow-up. The Cox hazard model analysis demonstrated that male gender, CAD at the baseline, and parental CAD were related to the development of atherosclerotic cardiovascular disease (ASCVD) events. Furthermore, an increase in serum HDL-C was associated with a significant reduction of ASCVD events, while serum LDL-C and triglyceride levels were not related to ASCVD events.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2009

Year

09

Month

01

Day

Date of IRB

2009

Year

09

Month

01

Day

Anticipated trial start date

2009

Year

09

Month

15

Day

Last follow-up date

2014

Year

12

Month

01

Day

Date of closure to data entry

2014

Year

12

Month

01

Day

Date trial data considered complete

2014

Year

12

Month

01

Day

Date analysis concluded

2014

Year

12

Month

01

Day

Other related information

Prospective study (observation)

Registered date

2010

Year

02

Month

19

Day

Last modified on

2021

Year

03

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003893