Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05579626
Other study ID # 2022-1275
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date March 14, 2023
Est. completion date December 30, 2027

Study information

Verified date December 2023
Source Asan Medical Center
Contact Su-Bin Shin, RN
Phone 8272577718
Email tls7718@naver.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study is to evaluating the impact of low-intensity statin plus ezetimibe versus high-intensity statin therapy on risk of new-onset diabetes mellitus in patients with atherosclerotic cardiovascular disease who have prediabetes.


Description:

The PROVE-DM trial is a multi-center, open-labeled, randomized controlled trial comparing two different lipid lowering strategies in patients with prediabetes and established atherosclerosis. Patients with prediabetes and documented atherosclerosis, either clinical or unequivocal on imaging are eligible for enrollment. The detailed information for inclusion and exclusion criteria is described below in the session 4. Patients meeting inclusion criteria without any exclusion criteria are assessed to be able to tolerate high-intensity statin therapy while achieving the target LDL level (LDL cholesterol < 70 mg/dL for established atherosclerotic cardiovascular disease or LDL cholesterol < 100 mg/dL for mild to moderate coronary artery disease) through a run-in period of 2 to 6 months. (Run in period was set as a screening process to reduce drop-out cases that cannot withstand high-intensity statins or cannot accomplished target LDL levels) Eligible patients will be randomized to high-intensity statin (rosuvastatin 20 mg qd) or low-intensity statin plus ezetimibe (rosuvastatin/ezetimibe 5/10 mg qd). Patients will be followed-up clinically at 6, 12 months and then annually up to 3 years after randomization. Follow-up measurement of DM diagnostic criteria (fasting plasma glucose, plasma Hb A1c, oral glucose tolerance test) and lipid profile is intended to 1) provide evidence of new onset DM, 2) evaluate effectiveness of lowering LDL cholesterol. To ensure the accurate assessment of the clinical outcomes, cardiovascular safety end point (death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke), any arterial revascularization, any potential side effects of statin and all-cause mortality were also investigated.


Recruitment information / eligibility

Status Recruiting
Enrollment 4000
Est. completion date December 30, 2027
Est. primary completion date December 30, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: 1. Men or women between the ages of 18 and 75 years who have prediabetes -Prediabetes consists of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or HbA1c 1. IFG: fasting plasma glucose (FPG) 100 to 125 mg/dL 2. IGT: 2 hours post-load glucose on the 75g OGTT (oral glucose tolerance test) 140 to 199 mg/dL 3. HbA1c: 5.7 to 6.4% 2. Patient requiring high-intensity statin due to high risk of a future cardiovascular event if at least one of the following criteria is present via patient history, physical examination, or medical records at the time of screening (Clinically documented ASCVD) - acute coronary syndrome (MI or unstable angina) - stable angina - coronary revascularization (PCI, CABG, and other arterial revascularization procedure) - stroke or TIA - peripheral arterial disease (<0.9 performed by a vascular lab or angiogram (including CTA) showing = 50%) Unequivocally documented ASCVD on imaging - significant plaque on coronary angiography on CT (mild, moderate, severe coronary artery disease) - significant plaque on carotid ultrasound (mild, moderate, severe carotid disease) 3. Patients who have never taken a statin or who do not have problems adhering to statin therapy 4. Patient must have been on a stable diet prior to randomization and willing to follow the NCEP (national Cholesterol Education Program) TLC (therapeutic lifestyle changes) diet, or equivalent diet, throughout the study. 5. The patient or guardian agrees to the study protocol and the schedule of clinical follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site. Exclusion Criteria: 1. Patient's pregnant or breast-feeding or child-bearing potential. 2. Concomitant administration of potent inhibitors of CYP3A4 (itraconazole, ketoconazole, protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone) or CYP2C9 (relative contraindication not dependent on CYP450 statins). 3. Chronic kidney disease (eGFR<30 ml/min/1.73m2) or dialysis-dependent renal failure 4. Uncontrolled hypothyroidism. 5. Personal or family history of hereditary muscular disorders. 6. History of muscular toxicity with a statin 7. Alcoholism. 8. Hypersensitivity to any of statin and ezetimibe. 9. Hemodynamic unstable conditions at the time of inclusion: cardiogenic shock at the time of randomization, refractory ventricular arrhythmias, or congestive heart failure (New York Heart Association class IV). 10. Any history of hemorrhagic stroke or intracranial hemorrhage within the past 6 months 11. Any surgery requiring discontinuation of statin and/or ezetimibe is planned within 6 months after randomization 12. A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer. 13. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study. 14. Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal) or (Total bilirubin> 2 times upper limit of normal). 15. Life expectancy < 1 years for any non-cardiac or cardiac causes 16. Unwillingness or inability to comply with the procedures described in this protocol. 17. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period. 18. People who have previously been diagnosed with diabetes and are taking lifestyle modification and oral hypoglycemic agent (OHA) or insulin (In woman, gestational diabetes is included)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
high-intensity statin arm
•high-intensity statin strategy (standard arm): rosuvastatin 20 mg PO qd, once daily
low-intensity statin plus ezetimibe
•low-intensity statin plus ezetimibe strategy (experimental arm): rosuvastatin 5mg /ezetimibe 10mg PO qd), once daily

Locations

Country Name City State
Korea, Republic of Bycheon Sejong Hospital Bucheon
Korea, Republic of Gyeongsang National University Changwon Hospital Changwon
Korea, Republic of Chungbuk National University Hospital Cheonju
Korea, Republic of Gangwon National University Hospital Chuncheon
Korea, Republic of Daegu Catholic University Medical Center Daegu
Korea, Republic of Keimyung University Dongsan Medical Center Daegu
Korea, Republic of Chungnam National University Sejong Hospital Daejeon
Korea, Republic of Gangneung Asan Hospital Gangneung
Korea, Republic of Gachon University Gil Medical Center Incheon
Korea, Republic of Jeju National University Hospital Jeju
Korea, Republic of Dong-A Medical Center Pusan
Korea, Republic of Inje University Busan Paik Hospital Pusan
Korea, Republic of Kosin University Gospel Hospital Pusan
Korea, Republic of Pusan National University Yangsan Hospital Pusan
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Hallym University Medical Center-Kangdong Seoul
Korea, Republic of Korea University Anam Hospital Seoul
Korea, Republic of The Catholic Univ. of Korea Eunpyeong St. Mary's hospital Seoul
Korea, Republic of The Catholic University of Korea, St. Vincent's Hospital Suwon
Korea, Republic of Ulsan University Hospital Ulsan

Sponsors (2)

Lead Sponsor Collaborator
Seung-Whan Lee, M.D., Ph.D. Yuhan Corporation

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants with New-onset-DM New onset DM was defined on the the basis of the American Diabetes association guideline if two abnormal test results of following criteria are existed from the same sample or in two separate test samples.
fasting plasma glucose (FPG) =126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours OR
2 hour plasma glucose during a 75 g oral glucose tolerance test (OGTT) =200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water OR
HbA1C =6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP (National Glycohemoglobin Standardization Program) certified and standardized to the DCCT (Diabetes Control and Complication Trial) assay.
36months after randomization
Primary Number of Participants with death Major adverse cardiac events are defined as all-cause death 36months after randomization
Secondary Composite cardiovascular safety death from cardiovascular cause, non fatal myocardial infarction of nom fatal stroke 36months after randomization
Secondary Any arterial revascularization Any arterial revascularization (carotid, coronary aorta or peripheral artery) Any arterial revascularization (carotid, coronary aorta or peripheral artery) 36months after randomization
Secondary Any potential side effect Any potential side effect 36months after randomization
Secondary Each component of the diabetes-mellitus diagnosis criteria Each component of the diabetes-mellitus diagnosis criteria 36months after randomization
Secondary All cause mortality All cause mortality 36months after randomization
See also
  Status Clinical Trial Phase
Recruiting NCT05052918 - The Effect of Exercise and Metformin on Carotid Intima-media Thickness in Patients With Prediabetes N/A
Completed NCT03714646 - Beta Glucan and Acetate Production N/A
Completed NCT03377244 - Healthy Body Healthy Souls in the Marshallese Population N/A
Completed NCT04427982 - Dance and Diabetes/Prediabetes Self-Management N/A
Recruiting NCT05008276 - Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress (PANTHER Study)
Completed NCT03480022 - Liraglutide 3mg (Saxenda) on Weight, Body Composition, Hormonal and Metabolic Parameters in Obese Women With PCOS Phase 3
Active, not recruiting NCT05290233 - Time Restricted Eating Plus Exercise for Weight Management N/A
Withdrawn NCT05726409 - Mobile Application to Create Healthy Food Preparation Habits for Patients With Diabetes and Prediabetes N/A
Completed NCT02834078 - Effect of BGG on Glucose Metabolism and Other Markers of Metabolic Syndrome N/A
Completed NCT04902326 - Behavioral Economics and Self-Determination Theory to Change Diabetes Risk (BEST Change) N/A
Recruiting NCT04168372 - Fructose: Substrate, Stimulus, or Both? N/A
Completed NCT03272074 - Egg Consumption and Glycemic Control in Individuals With Pre- and Type II-diabetes N/A
Not yet recruiting NCT05939349 - A Prescription for Health Equity: A Healthcare Provider-based Produce Prescription Program for People With Prediabetes and Type 2 Diabetes N/A
Completed NCT04978376 - TRE With Physical Activity for Weight Management N/A
Recruiting NCT03997656 - A Digital Therapy for Diabetes Prevention Among Overweight Adults in Terengganu, Malaysia N/A
Recruiting NCT05166785 - BRInging the Diabetes Prevention Program to GEriatric Populations N/A
Completed NCT01729078 - Dietary Interventions in Prediabetes N/A
Completed NCT04507685 - Asian Indian Prediabetes Study N/A
Completed NCT03292315 - Once Weekly GLP-1 in Persons With Spinal Cord Injury Phase 4
Active, not recruiting NCT05353790 - Dietary Exchanges With Avocado and Mango in Pre-diabetes N/A