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

• ClinicalTrials.gov Identifier: NCT05910476
• Recruitment Status: Recruiting
• First Posted: June 18, 2023
• Last Update Posted: March 15, 2024
• Sponsor: Yonsei University
• Collaborator: dotter
• Information provided by (Responsible Party): Deok-Kyu Cho, Yonsei University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease; Dyslipidemias	Drug: a high dose of statin/ezetimib	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 3, 2023
• Estimated Primary Completion Date: September 22, 2026
• Estimated Study Completion Date: September 22, 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: rosuvastatin/ezetimibe 20/10mg; rosuzet 10/20mg	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.
Active Comparator: atorvastatin/ezetimibe 40/10mg; NB zet 10/40mg	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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of statins changed [ Time Frame: 12 months ]
   Percentage of statins changed to discontinuation or intolerance (muscle pain, muscle efficiency, elevated liver level, etc.) within a year
2. Rate at which LDL cholesterol remains below 55 mg/dL [ Time Frame: 12 months ]
   Rate at which LDL cholesterol remains below 55 mg/dL in all 1-year blood tests

Secondary Outcome Measures :

1. The rate at which LDL cholesterol is maintained at 55 mg/dL in the blood test after a month [ Time Frame: 1 months ]
   The rate at which LDL cholesterol is maintained at 55 mg/dL in the blood test after a month
2. Cardiovascular death [ Time Frame: 12 months ]
   Cardiovascular death
3. number of non-fatal myocardial infarction [ Time Frame: 12 months ]
   number of non-fatal myocardial infarction
4. number of non-fatal stroke [ Time Frame: 12 months ]
   number of non-fatal stroke
5. number of coronary artery re-perfusion [ Time Frame: 12 months ]
   number of coronary artery re-perfusion
6. number of Newly developed diabetes or difficulty in controlling sugar [ Time Frame: 12 months ]
   number of Newly developed diabetes or difficulty in controlling sugar
7. occurrence of statin-related muscle symptoms requiring therapeutic or dose changes [ Time Frame: 12 months ]
   occurrence of statin-related muscle symptoms requiring therapeutic or dose changes
8. Increased muscle enzyme aberration [ Time Frame: 12 months ]
   Increased muscle enzyme aberration (CPK > 4 x normal upper limit)
9. Elevated liver enzyme levels [ Time Frame: 12 months ]
   Elevated liver enzyme levels (AST, ALT, or both ≥ 3 x normal upper bound)
10. Elevated serum creatine levels [ Time Frame: 12 months ]
    Elevated serum creatine levels (from >50% baseline)
11. number of Major bleeding [ Time Frame: 12 months ]
    number of Major bleeding
12. number of people who stopped taking the drug [ Time Frame: 12 months ]
    number of people who stopped taking the drug

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: deok kyu CHO, MD; +82-31-5189-8755; CHODK123@yuhs.ac

Contact: Yongcheol Kim, MD; +82-31-5189-8786; decenthyun@yuhs.ac

Locations

Korea, Republic of

Yongin Severance Hospital; Recruiting

Yongin, Gyeonggi-do, Korea, Republic of, 16995

Contact: deok kyu CHO, MD +82-31-5189-8755 CHODK123@yuhs.ac

Sponsors and Collaborators

Yonsei University

dotter

Investigators

• Study Director: Yongcheol Kim, MD; Yonsei University

More Information

• Responsible Party: Deok-Kyu Cho, Professor, Yonsei University
• ClinicalTrials.gov Identifier: NCT05910476
• Other Study ID Numbers: 9-2023-0008
• First Posted: June 18, 2023
• Last Update Posted: March 15, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Coronary Artery Disease; Dyslipidemias; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Ezetimibe; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents