Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
- Author:
Nam Hoon KIM
1
;
Juneyoung LEE
;
Suk CHON
;
Jae Myung YU
;
In-Kyung JEONG
;
Soo LIM
;
Won Jun KIM
;
Keeho SONG
;
Ho Chan CHO
;
Hea Min YU
;
Kyoung-Ah KIM
;
Sang Soo KIM
;
Soon Hee LEE
;
Chong Hwa KIM
;
Soo Heon KWAK
;
Yong‐ho LEE
;
Choon Hee CHUNG
;
Sihoon LEE
;
Heung Yong JIN
;
Jae Hyuk LEE
;
Gwanpyo KOH
;
Sang-Yong KIM
;
Jaetaek KIM
;
Ju Hee LEE
;
Tae Nyun KIM
;
Hyun Jeong JEON
;
Ji Hyun LEE
;
Jae-Han JEON
;
Hye Jin YOO
;
Hee Kyung KIM
;
Hyeong-Kyu PARK
;
Il Seong NAM-GOONG
;
Seongbin HONG
;
Chul Woo AHN
;
Ji Hee YU
;
Jong Heon PARK
;
Keun-Gyu PARK
;
Chan Ho PARK
;
Kyong Hye JOUNG
;
Ohk-Hyun RYU
;
Keun Yong PARK
;
Eun-Gyoung HONG
;
Bong-Soo CHA
;
Kyu Chang WON
;
Yoon-Sok CHUNG
;
Sin Gon KIM
Author Information
- Publication Type:Original Article
- From:Endocrinology and Metabolism 2024;39(5):722-731
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion:This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
