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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 2019

Detailed Description

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).

Interventions

  • Drug: Pitavastatin Calcium
    • 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.
  • Drug: Atorvastatin Calcium
    • 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.

Arms, Groups and Cohorts

  • Experimental: pitavastatin
    • Pitavastatin Calcium + lifestyle modification
  • Active Comparator: atorvastatin
    • Atorvastatin Calcium + lifestyle modification

Clinical Trial Outcome Measures

Primary Measures

  • Change from baseline in hemoglobin A1c levels
    • Time Frame: Month 12
    • Change of HbA1C values at study initiation and study completion

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

1. Age 18-80 years old; 2. 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); 3. 2.6mmol/L (100mg/dl)≤LDL-C≤5.2mmol/L (200mg/dl), and TG<5.7mmol/L (500mg/dl); 4. 130mmHg≤SBP<180mmHg, or 80mmHg≤DBP<110mmHg or ongoing anti-hypertensive therapy; 5. Patients volunteered for the study and signed informed consent. Exclusion Criteria:

1. Past history of hypersensitivity to the study drug; 2. Diagnosed diabetes; 3. Severe liver disease (including ALT or AST≥2.5-fold the normal upper limit), biliary obstruction; 4. Ongoing treatment with cyclosporine within 2 weeks; 5. 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; 6. Diagnosed or past history of ASCVD (including ACS, SCAD, revascularization, ICM, ischemic stroke, TIA, PASD, etc. 7. SBP≥180mmHg, or DBP≥110mmHg; 8. Ongoing treatment with Beta blockers, Diuretic; 9. Secondary hypertension, including SAS, PA, RAS, pheochromocytoma, Cushing's syndrome, aorta diseases, drug induced hypertension; 10. Ongoing treatment with statins, fibrates, and/or cation exchange resins within 2 weeks; 11. Pancreatic disease; 12. History of gastrectomy, short bowel syndrome; 13. Ongoing hormone replacement therapy; 14. Diagnosed or suspected malignant tumor; 15. Familial hypercholesterolemia; 16. Any diseases may limit the efficacy or safety of the study; 17. Pregnant or possibly pregnant woman, or breastfeeding woman, or woman who wishes to become pregnant during study participation; 18. 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Jun Tao
  • Collaborator
    • Sun Yat-sen University
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Jun Tao, Director, Head of the Department of Hypertension and Cardiovascular Disease, Principal Investigator, Clinical Professor – First Affiliated Hospital, Sun Yat-Sen University
  • Overall Official(s)
    • Jun Tao, MD,PhD, Study Chair, First Affiliated Hospital, Sun Yat-Sen University
  • Overall Contact(s)
    • Jun Tao, MD,PhD, +8613922191609, taojungz123@163.com

References

Maki KC, Ridker PM, Brown WV, Grundy SM, Sattar N, The Diabetes Subpanel of the National Lipid Association Expert Panel. An assessment by the Statin Diabetes Safety Task Force: 2014 update. J Clin Lipidol. 2014 May-Jun;8(3 Suppl):S17-29. doi: 10.1016/j.jacl.2014.02.012.

Yusuf S, Lonn E, Pais P, Bosch J, Lopez-Jaramillo P, Zhu J, Xavier D, Avezum A, Leiter LA, Piegas LS, Parkhomenko A, Keltai M, Keltai K, Sliwa K, Chazova I, Peters RJ, Held C, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Accini JL, McKelvie R, Pogue J, Jung H, Liu L, Diaz R, Dans A, Dagenais G; HOPE-3 Investigators. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2032-43. doi: 10.1056/NEJMoa1600177. Epub 2016 Apr 2. Erratum In: N Engl J Med. 2018 Oct 11;379(15):1486.

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Warita S, Kawasaki M, Tanaka R, Ono K, Kojima T, Hirose T, Iwama M, Watanabe T, Nishigaki K, Takemura G, Noda T, Watanabe S, Minatoguchi S. Effects of pitavastatin on cardiac structure and function and on prevention of atrial fibrillation in elderly hypertensive patients: a prospective study of 2-years' follow-up. Circ J. 2012;76(12):2755-62. doi: 10.1253/circj.cj-12-0722. Epub 2012 Aug 8.

Yoshika M, Komiyama Y, Masuda M, Yokoi T, Masaki H, Ohkura H, Takahashi H. Pitavastatin further decreases serum high-sensitive C-reactive protein levels in hypertensive patients with hypercholesterolemia treated with angiotensin II, type-1 receptor antagonists. Clin Exp Hypertens. 2010;32(6):341-6. doi: 10.3109/10641961003628460.

Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F; Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003 Jan 28;107(3):499-511. doi: 10.1161/01.cir.0000052939.59093.45. No abstract available.

Kushiro T, Mizuno K, Nakaya N, Ohashi Y, Tajima N, Teramoto T, Uchiyama S, Nakamura H; Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese Study Group. Pravastatin for cardiovascular event primary prevention in patients with mild-to-moderate hypertension in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. Hypertension. 2009 Feb;53(2):135-41. doi: 10.1161/HYPERTENSIONAHA.108.120584. Epub 2008 Dec 22.

Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. doi: 10.1056/NEJMoa0807646. Epub 2008 Nov 9.

Ridker PM, Macfadyen JG, Nordestgaard BG, Koenig W, Kastelein JJ, Genest J, Glynn RJ. Rosuvastatin for primary prevention among individuals with elevated high-sensitivity c-reactive protein and 5% to 10% and 10% to 20% 10-year risk. Implications of the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial for "intermediate risk". Circ Cardiovasc Qual Outcomes. 2010 Sep;3(5):447-52. doi: 10.1161/CIRCOUTCOMES.110.938118. Epub 2010 Aug 24.

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