UMIN-CTR Clinical Trial

Basic information
Public title	Clinical test to examine the efficacy and safety of pemafibrate
Acronym	PEMA Trial
Scientific Title	Efficacy and safety of pemafibrate in high risk patients with coronary artery disease
Scientific Title:Acronym	PEBE Trial
Region	Japan

Condition
Condition	Hypertriglyceridemia
Classification by specialty	Medicine in general Cardiology Endocrinology and Metabolism Adult
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To examine the efficacy and safety with pemafibrate treatment compared with those of bezafibrate
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Others
Trial characteristics_2	Others
Developmental phase	Not applicable

Assessment
Primary outcomes	To examine a percent change in the fasting serum triglyceride levels from baseline to the study endpoint after the 24-week treatment with bezafibrate or pemafibrate.
Key secondary outcomes	To examine a percent change in the fasting serum HDL-C and ApoA-1 levels from baseline to study endpoint.

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
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Patients were randomly assigned in a 1:1 ratio to two treatments: bezafibrate of 400 mg/day or pemafibrate of 0.2 mg/day for the first 24-week treatment period.
Interventions/Control_2	Patients were randomly assigned in a 1:1 ratio to two treatments: bezafibrate of 400 mg/day or pemafibrate of 0.2 mg/day for the first 24-week treatment period.
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	75 years-old >=
Gender	Male and Female
Key inclusion criteria	Eligible patients were men and postmenopausal women aged 20-75 years with dyslipidemia treated with statin and CAD who showed fasting serum TG levels of > 150 mg/dL and HDL-C levels of < 50 mg/dL in men or < 55 mg/dL in women at entry.
Key exclusion criteria	1.patients who required additional medication for dyslipidemia during the study period 2.fasting serum TG levels of over than 1000 mg/dl 3.type 1 diabetes mellitus or uncontrolled type 2 DM (HbA1c level of over than 8.5%) 4.familiar hypercholesterolemia 5.chronic kidney disease showing a serum creatinine level of over than 1.5 mg/dL 6.history or complication of gallbladder disease, cholelithiasis, pancreatitis, and malignant tumor 7.aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation to a level more than two times the upper limit of normal (ULN) range 8.uncontrolled hypertension (systolic blood pressure BP ofover tahn 160 mmHg or diastolic BP of over than 100 mmHg) 9.hemoglobin level of less than 12g/dL in men or less than 11 g/dL in women 11.recent myocardial infarction or cerebrovascular disorder within 3 months before the study 12.hospitalization for worsening heart failure within 3 months 13.use of ezetimibe and supplements containing eicosapentaenoic acid, and/or docosahexaenoic acid within 3 months before the study. Patients were also prohibited from using agents that affect lipid metabolism,such as thiazolidinedione, insulin,oral corticosteroid, or protease inhibitor.
Target sample size	60

Research contact person
Name of lead principal investigator	1st name Akihiro Middle name Last name Nakamura
Organization	Iwate Prefectural Central Hospital
Division name	Department of Cardiology
Zip code	020-0066
Address	1-4-1 Ueda, Morioka, Japan
TEL	0196531151
Email	akihiro-nakamura@pref.iwate.jp

Public contact
Name of contact person	1st name Akihiro Middle name Last name Nakamura
Organization	Iwate Prefectural Central Hospital
Division name	Department of Cardiology
Zip code	020-0066
Address	1-4-1 Ueda, Morioka, Japan
TEL	0196531151
Homepage URL
Email	akihiro-nakamura@pref.iwate.jp

Sponsor
Institute	Department of Cardiology, Iwate Prefectural Centgral Hospital
Institute
Department

Funding Source
Organization	Iwate Prefectural Centgral Hospital
Organization
Division
Category of Funding Organization	Local Government
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	Iwate Prefectural Central Hospital
Address	1-4-1 Ueda, Morioka, Japan
Tel	0196531151
Email	akihiro-nakamura@pref.iwate.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	岩手県立中央病院　循環器内科

Other administrative information
Date of disclosure of the study information	2022 Year 05 Month 13 Day

Related information
URL releasing protocol	https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_63659/_pdf/-char/en
Publication of results	Published

Result
URL related to results and publications	https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_63659/_pdf/-char/en
Number of participants that the trial has enrolled	60
Results	The %Change in TG and Apo A-I levels was significantly greater with pemafibrate than with bezafibrate (-46.1% vs. -34.7%, p<0.001; 9.2% vs. 5.7%, p=0.018, respectively). %Change in HDL-C levels was not significantly different between the two treatments. %Change in liver enzyme levels was markedly decreased with pemafibrate than with bezafibrate.
Results date posted	2022 Year 11 Month 21 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	The mean age was 63 years, and 92% (n=55) of the patients were men. The mean body mass index was 27 kg/m2, and 77% (n=46) of the patients met the Japanese criteria for MetS. Approximately 40% (n=24) of the patients had type 2 DM and 80% (n=48) had hypertension. Nearly half of the patients (n=31, 52%) received rosuvastatin as statin therapy.
Participant flow	Of 78 patients initially screened, 60 were enrolled and randomized with 30 patients per treatment. All 60 patients completed the study and were included in both analysis sets.
Adverse events	The incidence rates of AEs were 37% (n=22) and 43% (n=26) with bezafibrate and pemafibrate treatments, respectively. Treatment related AEs occurred in one patient in each treatment group: thickening of the gallbladder with bezafibrate treatment and hot flash with pemafibrate treatment. In the bezafibrate treatment group, SAEs occurred in five patients, of which two were related to the treatment: worsening renal function and acute cholecystitis. Conversely, in the pemafibrate treatment group, SAEs occurred in six patients, but none were related to the treatment. There were no treatment discontinuations because of AEs or SAEs.
Outcome measures	The primary efficacy endpoint was a percent change (%Change) in the fasting serum TG levels from baseline to the study endpoint after the 24-week treatment with bezafibrate or pemafibrate. The baseline and study endpoint were defined as measurements before and after the 24-week treatment, respectively. The secondary efficacy endpoints were %Change in the fasting serum HDL-C and Apo A-I levels from baseline to the study endpoint.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2019 Year 10 Month 30 Day
Date of IRB	2019 Year 10 Month 30 Day
Anticipated trial start date	2020 Year 02 Month 01 Day
Last follow-up date	2021 Year 07 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2022 Year 05 Month 12 Day
Last modified on	2022 Year 11 Month 21 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054422