UMIN-CTR Clinical Trial

Basic information
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
Condition	familial hypercholesterolemia
Classification by specialty	Medicine in general Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute	Osaka University Graduate School of Medicine
Institute
Department

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

Other related organizations
Co-sponsor
Name of secondary funder(s)

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

Institutions

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）

Other administrative information
Date of disclosure of the study information	2010 Year 02 Month 19 Day

Related information
URL releasing protocol	https://www.jstage.jst.go.jp/browse/jat/-char/ja/
Publication of results	Published

Result
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

Progress
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
Other related information	Prospective study (observation)

Management information
Registered date	2010 Year 02 Month 19 Day
Last modified on	2021 Year 03 Month 02 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000003893