Clinical Comparison of Low-dose Rosuvastatin Plus Ezetimibe Combination Therapy and High-dose Rosuvastatin Monotherapy in Patients With Minimal to Intermediate Coronary Artery Disease Without Percutaneous Coronary Intervention (ALMIGHTY)

Clinical Comparison of Low-dose Rosuvastatin Plus Ezetimibe Combination Therapy and High-dose Rosuvastatin Monotherapy in Patients With Minimal to Intermediate Coronary Artery Disease Without Percutaneous Coronary Intervention : A Prospective, Multicenter, Randomized, Open-label Trial

[Purpose of the Clinical Study]:The purpose of this study is to conduct a clinical comparison of low-dose rosuvastatin plus ezetimibe combination therapy and high-dose rosuvastatin monotherapy in patients with minimal to intermediate coronary artery disease without percutaneous coronary intervention to confirm non-inferiority in the reduction of key cardiovascular events.

[Hypothesis]:In patients who have not undergone percutaneous coronary intervention for minimal to moderate coronary artery disease, low-dose rosuvastatin and ezetimibe combination therapy are non-inferior in terms of reducing major cardiovascular events compared to high-dose rosuvastatin monotherapy.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Dyslipidemias; Primary Prevention
• Intervention / Treatment: Drug: Combination drug group of Ezetimibe 10 mg/Rosuvastatin 5 mg; Drug: Mono drug group of Rosuvastatin 20 mg

Detailed Description

[Background]:While high-dose statin is becoming more important, there are factors that limit more widespread use of such a treatment due to the possibility of adverse events, especially among the patients from East Asia. These factors include muscle-related diseases, higher liver figures, and onset of diabetes. Meanwhile, the combination treatment of low-dose statin and ezetimibe, which slows down the absorption of LDL cholesterol, can see an equivalent level of LDL cholesterol reduction compared to high-dose statin treatments, while having an advantage in terms of the level of decrease in adverse events. However, further verification is still needed whether the statin + ezetimibe combination therapy and the high-dose statin monotherapy of the same reduction effect against LDL cholesterol would have the same level of clinical utility. Especially with regard to the treatment of patients with minimal to minor coronary artery diseases, there are no available guidelines for the use of statin. In the case of a stenosis lesion with a 50 to 70% severity level, the likelihood of choosing medication over percutaneous coronary artery interventions through a physiological evaluation is increasing compared to the past. Also, some studies suggested that the MACE of an intermediate lesion showed a difference depending on the administration of statin, while percutaneous coronary intervention did not. Therefore, verification of the clinical utility on the said lesions is also necessary.

[Clinical Research Plan]: A prospective, multicenter, randomized, and public label clinical study involving a total of 6,356 patients, 3,178 patients each with ezetimibe 10mg/rosuvastatin 5mg (experimental group) and rosuvastatin 20mg (active control group), in patients who have not undergone percutaneous coronary intervention for minimal to moderate coronary artery disease. After random assignment, take the assigned drugs for 3 years and follow-up observation is conducted at 6weeks, 6, 12, and 36 months. Test personnel can follow up through hospital visits or phone visits. The primary end-points are a combined assessment variable of all cause death, cardiovascular deaths, myocardial infarction without death, stroke without death, hospitalization due to unstable angina, and revascularization after random assignment at 36 months.

• Study Type: Interventional
• Enrollment (Estimated): 6356
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sung-ho Her, MD.PhD; Phone Number: 821077310052; Email: hhhsungho@naver.com
• Study Contact Backup: Name: Jung Jin, MD; Phone Number: 821087238603; Email: colaking@naver.com

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of, 16247
      • Recruiting
      • St. Vincent's Hospital
      • Contact: Sung-ho Her, MD.PhD; Phone Number: 821077310052; Email: hhhsungho@naver.com
      • Contact: Jung Jin, MD; Phone Number: 821087238603; Email: colaking@naver.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female adjusts (19 or older)
2. Patients with suspected stable angina pectoris without coronary artery interventions, who showed a minimal to intermediate coronary artery diseases (a stenosis of 10 to 70% diameter as per QCA) in at least one natural coronary artery in coronary artery angiography or coronary artery CT.
3. Patients who gave their informed consent themselves in writing.
4. Patients who were treated with statin or lipid-lowering agents may participate in the study by changing the existing medicines.

Exclusion Criteria:

1. Patients with an intermediate (>30%) lesion on the left main coronary artery.
2. Patients diagnosed with acute coronary artery diseases (STEMI, NSTEMI, Unstable angina)
3. Patients who received percutaneous coronary intervention
4. Patients who have been diagnosed with stroke, transitory ischemic attack, and peripheral artery diseases.
5. Patients diagnosed with variant angina
6. Patients with severe liver diseases or lung diseases and/or malignant tumor
7. Patients with severe valvular heart disease
8. Patients who are hypersensitive or prohibited from using the active substance (Ezetimibe or Rosuvastatin) of the study medicines
9. Patients whose remaining life expectancy is less than a year
10. Patients with cardiogenic shock
11. Pregnant women or women who are planning to get pregnant
12. Patients who are receiving hemodialysis or peritoneal dialysis or received renal transplantation due to end-stage renal failure
13. Patients who participated in other clinical studies within the past three months (except for non-interventional observation studies)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination drug group of Ezetimibe 10 mg/Rosuvastatin 5 mg; Ezetimibe 10 mg/Rosuvastatin 5 mg, Oral administration once a day, taking it for 3 years	Drug: Combination drug group of Ezetimibe 10 mg/Rosuvastatin 5 mg; Oral administration once a day, taking it for 3 years
Active Comparator: Mono drug group of Rosuvastatin 20 mg; Rosuvastatin 20 mg , Oral administration once a day, taking it for 3 years	Drug: Mono drug group of Rosuvastatin 20 mg; Oral administration once a day, taking it for 3 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence rates of the compound variables	The occurrence rates of the compound variables of all cause deaths, cardiac deaths, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina, and revascularization after taking the study medicine at the time of Visit 5 (36 month) were compared between groups	Visit 5 (36month)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of satisfying the target	The rate of satisfying the target for low-density cholesterol at Month 36. (Patients with intermediate coronary artery diseases and 50% or higher stenosis: LDL-C less than 70mg/dL, Patients with less than 50% stenosis, intermediate coronary artery diseases, or diabetes: The LDL-C level is less than the target, which is 100mg/dL.); The occurrence rate of myopathy related to statin at Month 36.; Drop-out rate of the test drug during the study periodBecause the outcome parameters measured in our study have a consensus on their definitions, there is no possibility of potentially different Units of Measure. Additionally, LDL already clearly presents the units, so there is no need for separate Outcome Measures.	Visit 5 (36month)
Compound end-point	Compound end-points of all cause deaths, cardiac deaths, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina, and revascularization after randomization; All cause deaths , Cardiac deaths, Non-fatal myocardial infarction, Non-fatal stroke, Hospitalization due to unstable angina, Revascularization after randomization; The satisfaction rate of low-density cholesterol target at visit 6 weeks, 12th month. (Patients with intermediate coronary artery diseases and 50% or higher stenosis: LDL-C less than 70mg/dL, Patients with less than 50% stenosis, intermediate coronary artery diseases, or diabetes: The LDL-C level is less than the target, which is 100mg/dL.); The frequency of myopathy related to statin at visit 6 weeks, 12th month; Drop-out rate of the test drug during the study periodBecause the outcome parameters measured in our study have a consensus on their definitions, there is no possibility of potentially different Units of Measure.	Visit 4 (12 month)

Collaborators and Investigators

• Sponsor: Saint Vincent's Hospital, Korea
• Investigators: Principal Investigator: Sung-ho Her, MD.PhD, St Vincent's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2029

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Actual): December 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Primary Prevention; Dyslipidemias
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Ezetimibe
• Other Study ID Numbers: XC23MIDV0033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No