Comparative Study of Rosuvastatin/Ezetimib 20/10 mg and Atovastatin/Ezetimib 40/10 mg (TOLERANT Trial)

Coronary Artery Disease Clinical Trial

Official title:

A Randomized comparaTive Study Of Rosuvastatin/Ezetimibe 20/10mg and Atorvastatin/Ezetimibe 40/10mg in Patients With Coronary Artery Drug eLuting stEnt Implantation Requiring High-dose stAtin/Ezetimibe combiNaTion Therapy: TOLERANT Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05910476
• Other study ID #: 9-2023-0008
• Status: Recruiting
• Phase: Phase 4
• Start date: May 3, 2023
• Est. completion date: September 22, 2026

Study information

• Verified date: March 2024
• Source: Yonsei University
• Contact: deok kyu CHO, MD
• Phone: +82-31-5189-8755
• Email: CHODK123[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

the investigators would like to compare the differences between roschvastin and atovastatin in patients who require high-dose statin/ejetimib to undergo a new generation of drug elution stent implantation for cardiovascular disease and maintain LDL cholesterol below 55 mg/dL.

Description:

Death from vascular disease accounts for about one-third of all causes of death. Important regulatory factors in cardiovascular disease include dyslipidemia, high blood pressure, and diabetes, and keeping LDL cholesterol low among dyslipidemia levels, especially after cardiovascular stent treatment, is an essential factor to prevent another event in the future. Statin is currently the most widely used LDL cholesterol control drug with multifunctional effects such as controlling inflammatory reactions, controlling the movement and proliferation of vascular smooth muscle cells, and inhibiting the production of blood clots in addition to LDL cholesterol control.In addition, in several clinical studies, statins have shown many effects in primary and secondary prevention of cardiovascular disease, and several studies have been published that lower LDL cholesterol results in more benefits. Based on these findings, the 2016 European Heart Association (ESC), 2018 American Heart Association (ACC), and most recently changed 2022 Korean guidelines recommend controlling LDL cholesterol to <55mg/dL for patients with coronary artery disease. However, high-dose statins alone are still difficult to maintain for a long time due to increased liver levels, diabetes, and muscle pain, and recently, a drug that lowers LDL cholesterol has been developed in the small intestine called Ezetimib and is widely used in combination with statins in actual clinical trials. In fact, the RACING trial published in LANCET for domestic patients reported that the combination of moderate-intensity statins (Rosuvastatin 10mg) and ezetimib had fewer side effects for three years and better compliance, resulting in a better rate of maintaining LDL cholesterol at 70mg/dL or less than high-intensity statins alone. However, in this study, the rate at which LDL cholesterol remained below 55 mg/dL after one year was only 42% for moderate statins/esetimibe and 25% for high-intensity statins, and remained similar for three years. Therefore, high-intensity statins and ezetimibes may be essential treatments to reduce LDL cholesterol to less than 55 mg/dL and more than 50% under the current new guidelines. High-strength statins usually refer to more than 40 mg of atovastatin and 20 mg of Rosuvastatin, and drugs that combine ezetimibe with these high-strength statins are currently widely used to lower LDL cholesterol to 55 mg/dL or less if there are no special side effects in clinical practice, but research on compliance is very insufficient. This study aims to observe the rate of discontinuation or intolerance in patients taking Rosuvastatin/Ezetimib 20/10mg and Atovastatin/Ezetimib 40/10mg, with no previous comparison, RACING trial reported a 5% rate of discontinuation at rosuvastain 20mg administered, and atovatin/10mg/10mg. Referring to On the use of a pilot sample for sample size determination. the hospital conducts about 60 PCI cases a month, and about 1/5 of them are expected to be able to enroll 100 patients per group for about two years to conduct a total of 200 patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: September 22, 2026
• Est. primary completion date: September 22, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. 19 years of age or older

2. Patients who underwent a new generation of drug elution stent implantation for cardiovascular disease

Exclusion Criteria:

1. LDL cholesterol levels below 55 mg/dL without statin treatment

2. Serum AST/ALT with an acute liver disease within a month or a normal upper limit that is not continuously explained

3. Allergies or overreactions to statins

4. Estimated Dawn of Less than 1 Year

5. If it is determined that follow-up is not possible for more than one year

6. Pregnancy

Related Conditions & MeSH terms

• Coronary Artery Disease
• Dyslipidemias

Intervention

Drug:
• a high dose of statin/ezetimib
In randomization, 100 patients will proceed with Rosuvastatin/Ezetimib 20/10 mg and 100 patients will proceed with Atovastatin/Ezetimib 40/10 mg. A new generation of drug elution stents can be inserted and later registered, and if the patient agrees to participate in the study, they are randomly assigned after stent implantation.

Locations

Country	Name	City	State
Korea, Republic of	Yongin Severance Hospital	Yongin	Gyeonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
Yonsei University	dotter

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of statins changed	Percentage of statins changed to discontinuation or intolerance (muscle pain, muscle efficiency, elevated liver level, etc.) within a year	12 months
Primary	Rate at which LDL cholesterol remains below 55 mg/dL	Rate at which LDL cholesterol remains below 55 mg/dL in all 1-year blood tests	12 months
Secondary	The rate at which LDL cholesterol is maintained at 55 mg/dL in the blood test after a month	The rate at which LDL cholesterol is maintained at 55 mg/dL in the blood test after a month	1 months
Secondary	Cardiovascular death	Cardiovascular death	12 months
Secondary	number of non-fatal myocardial infarction	number of non-fatal myocardial infarction	12 months
Secondary	number of non-fatal stroke	number of non-fatal stroke	12 months
Secondary	number of coronary artery re-perfusion	number of coronary artery re-perfusion	12 months
Secondary	number of Newly developed diabetes or difficulty in controlling sugar	number of Newly developed diabetes or difficulty in controlling sugar	12 months
Secondary	occurrence of statin-related muscle symptoms requiring therapeutic or dose changes	occurrence of statin-related muscle symptoms requiring therapeutic or dose changes	12 months
Secondary	Increased muscle enzyme aberration	Increased muscle enzyme aberration (CPK > 4 x normal upper limit)	12 months
Secondary	Elevated liver enzyme levels	Elevated liver enzyme levels (AST, ALT, or both = 3 x normal upper bound)	12 months
Secondary	Elevated serum creatine levels	Elevated serum creatine levels (from >50% baseline)	12 months
Secondary	number of Major bleeding	number of Major bleeding	12 months
Secondary	number of people who stopped taking the drug	number of people who stopped taking the drug	12 months