China Protection Trial of Glucose Metabolism by Pitavastatin in Patients With Prediabetes and Hypertension

Study Overview
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Brief Summary
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The primary purpose of this trial is to test the hypothesis that Pitavastatin treatment compared to Atorvastatin, in patients with dyslipidemia, prediabetes and hypertension, will have less adverse effect on Hemoglobin A1C (HbA1C), which represents long-term glucose metabolism.

Detailed Description
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Within the 12 months of the study procedure, the 3rd month is what we called the check point. At this point, participants' plasma LDL-C will be measured whether it reached individual standard or not. If the results didn't meet the particular LDL-C standard, the participants would be adjusted the drug dosage (pitavastatin 4mg/day, atorvastatin 40mg/day).

Official Title
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A Multi-center, Open-label, Randomized, 12-month, Parallel-group, Non-inferiority Study to Compare the Hemoglobin A1C Metabolism of Pitavastatin Therapy Versus Atorvastatin in Chinese Patients With Prediabetes and Hypertension

Conditions
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Prediabetic State, Hypertension, Dyslipidemias

Intervention / Treatment
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* Drug: Pitavastatin Calcium
* Drug: Atorvastatin Calcium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years old; IFG: 5.6mmol/L (100mg/dl)≤FPG<7.0mmol/L (126mg/dl), or IGT: 7.8mmol/L (140mg/dl)≤OGTT 2-h PG<11.1mmol/L (200mg/dl), or HbA1C 5.7-6.4% (39-47mmol/mol); 2.6mmol/L (100mg/dl)≤LDL-C≤5.2mmol/L (200mg/dl), and TG<5.7mmol/L (500mg/dl); 130mmHg≤SBP<180mmHg, or 80mmHg≤DBP<110mmHg or ongoing anti-hypertensive therapy; Patients volunteered for the study and signed informed consent. Exclusion Criteria: Past history of hypersensitivity to the study drug; Diagnosed diabetes; Severe liver disease (including ALT or AST≥2.5-fold the normal upper limit), biliary obstruction; Ongoing treatment with cyclosporine within 2 weeks; Renal dysfunction, including endogenous creatinine clearance male<120ml/min, female<105ml/min, serum creatinine≥2mg/dl (186umol/L), Renal function progressive decline, GFR<30ml•min-1•1.73m-2; Diagnosed or past history of ASCVD (including ACS, SCAD, revascularization, ICM, ischemic stroke, TIA, PASD, etc. SBP≥180mmHg, or DBP≥110mmHg; Ongoing treatment with Beta blockers, Diuretic; Secondary hypertension, including SAS, PA, RAS, pheochromocytoma, Cushing's syndrome, aorta diseases, drug induced hypertension; Ongoing treatment with statins, fibrates, and/or cation exchange resins within 2 weeks; Pancreatic disease; History of gastrectomy, short bowel syndrome; Ongoing hormone replacement therapy; Diagnosed or suspected malignant tumor; Familial hypercholesterolemia; Any diseases may limit the efficacy or safety of the study; Pregnant or possibly pregnant woman, or breastfeeding woman, or woman who wishes to become pregnant during study participation; Patient who was not judged as eligible by the investigator/coinvestigator. IFG impaired fast glucose, FPG fasting plasma glucose, IGT impaired glucose tolerance, OGTT oral glucose tolerance test, PG plasma glucose, HbA1C hemoglobin A1C, LDL-C low-density lipoprotein cholesterol, TG triglycerides, SBP systolic blood pressure, DBP diastolic blood pressure, ALT alanine aminotransferase, AST aspartate aminotransferase, GFR glomerular filtration rate, ASCVD arteriosclerotic cardiovascular disease, ACS acute coronary syndrome, SCAD stable coronary artery disease, ICM ischemic cardiomyopathy, TIA transient ischemic attack, PASD peripheral atherosclerotic disease, SAS sleep apnea syndrome, PA primary aldosteronism, RAS renal arterial stenosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pitavastatin<br>Pitavastatin Calcium + lifestyle modification | Drug: Pitavastatin Calcium<br>* In Pitavastatin treatment group, Pitavastatin calcium tablet 2mg/day was given for 12 months in combination with lifestyle modification. But month 3 is the check point. If LDL-C target was achieved at Month 3, doses remained the same. If LDL-C target was not achieved at Month 3, doses were doubled.<br>|
| Active Comparator: atorvastatin<br>Atorvastatin Calcium + lifestyle modification | Drug: Atorvastatin Calcium<br>* In Atorvastatin treatment group, Atorvastatin calcium tablet 20mg/day was given for 12 months in combination with lifestyle modification. But month 3 is the check point. If LDL-C target was achieved at Month 3, doses remained the same. If LDL-C target was not achieved at Month 3, doses were doubled.<br>* Other names: Lipitor®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in hemoglobin A1c levels | Change of HbA1C values at study initiation and study completion | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in FPG levels | Change of fasting plasma glucose (FPG) values at study initiation and study completion | Month 12 | 
| Changes from baseline in OGTT-2h PG levels | Change of oral glucose tolerance test (OGTT)-2h plasma glucose (PG) values at study initiation and study completion | Month 12 | 
| Proportion of subjects in LDL-C normalization state | Proportion of subjects in each group who achieved low-density lipoprotein cholesterol (LDL-C) target | Month 3 and 12 | 
| Changes from baseline in high-density lipoprotein cholesterol (HDL-C) levels | Change of HDL-C values at study initiation and study completion | Month 12 | 
| Changes from baseline in total cholesterol (TC) levels | Change of TC values at study initiation and study completion | Month 12 | 
| Changes from baseline in triglycerides (TG) levels | Change of TG values at study initiation and study completion | Month 12 | 
| Changes from baseline in inflammatory parameters | Change of C-reactive protein (CRP) values at study initiation and study completion | Month 12 | 
| Incidence of cardiovascular disease (CVD) events | Incidence of cardiovascular disease (CVD) events, including acute coronary syndrome, stable coronary artery disease, ischemic cardiomyopathy etc. | Month 12 | 
| Change from baseline in blood pressure levels | Change from baseline in systolic and diastolic blood pressure levels | Month 12 | 
| Changes from baseline in vascular endothelial function | Change of brachial-ankle pulse wave velocity (baPWV) values at study initiation and study completion | Month 12 | 
| Changes from baseline in left ventricular mass index | Change of left ventricular mass index (LVMI) values at study initiation and study completion | Month 12 | 
| Changes from baseline in carotid intima-media thickness | Change of carotid intima-media thickness (CIMT) values at study initiation and study completion | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pitavastatin, Prediabetic State, Hypertension, Dyslipidemias, Cardiovascular Disease