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

Hypertension Clinical Trial

— CAMPUS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03532620
• Other study ID #: BZ-1702
• Status: Recruiting
• Phase: Phase 4
• Start date: August 9, 2018
• Est. completion date: September 2020

Study information

• Verified date: May 2019
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: Jun Tao, MD,PhD
• Phone: +8613922191609
• Email: taojungz123[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 396
• Est. completion date: September 2020
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Dyslipidemias
• Hypertension
• Prediabetic State

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Fourth People's Hospital of Chongqing	Chongqing	Chongqing
China	First Affiliated Hospital of Jinan University	Guangzhou	Guangdong
China	First Affiliated Hospital,Sun Yat-sen University	Guangzhou	Guangdong
China	Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Lanzhou University Second Hospital	Lanzhou	Qinghai
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	Taizhou Hospital of TCM	Taizhou	Jiangsu
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	Subei People's Hospital of Jiangsu province	Yangzhou	Jiangsu
China	Yantaishan Hospital, Yantai	Yantai	Shandong
China	Yichang Central Hospital	Yichang	Hubei
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	People's Hospital of Zhongshan City	Zhongshan	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Jun Tao	Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (9)

Baudrand R, Pojoga LH, Vaidya A, Garza AE, Vöhringer PA, Jeunemaitre X, Hopkins PN, Yao TM, Williams J, Adler GK, Williams GH. Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects. Circulation. 2015 Nov 10;132(19):1825-33. doi: 10.1161/CIRCULATIONAHA.115.016759. Epub 2015 Oct 2. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2012 Aug 8. — View Citation

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. — View Citation

Yusuf S, Lonn E, Pais P, Bosch J, López-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events (AEs)	Incidence of adverse events (AEs) after treatment initiation	Month 12
Primary	Change from baseline in hemoglobin A1c levels	Change of HbA1C values at study initiation and study completion	Month 12
Secondary	Changes from baseline in FPG levels	Change of fasting plasma glucose (FPG) values at study initiation and study completion	Month 12
Secondary	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
Secondary	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
Secondary	Changes from baseline in high-density lipoprotein cholesterol (HDL-C) levels	Change of HDL-C values at study initiation and study completion	Month 12
Secondary	Changes from baseline in total cholesterol (TC) levels	Change of TC values at study initiation and study completion	Month 12
Secondary	Changes from baseline in triglycerides (TG) levels	Change of TG values at study initiation and study completion	Month 12
Secondary	Changes from baseline in inflammatory parameters	Change of C-reactive protein (CRP) values at study initiation and study completion	Month 12
Secondary	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
Secondary	Change from baseline in blood pressure levels	Change from baseline in systolic and diastolic blood pressure levels	Month 12
Secondary	Changes from baseline in vascular endothelial function	Change of brachial-ankle pulse wave velocity (baPWV) values at study initiation and study completion	Month 12
Secondary	Changes from baseline in left ventricular mass index	Change of left ventricular mass index (LVMI) values at study initiation and study completion	Month 12
Secondary	Changes from baseline in carotid intima-media thickness	Change of carotid intima-media thickness (CIMT) values at study initiation and study completion	Month 12