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A Multi-Center, Open-Label, Two-Arm Parallel Group Non-inferiority Randomized Controlled Trial Evaluating the Effect of Pitavastatin, Compared to Atorvastatin, on Glucose Metabolism in Prediabetics with Hypertension and Dyslipidemia: Rationale and Design for the China Hemoglobin A1c Metabolism Protection Union Study (CAMPUS)

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Abstract

Background

Hypertension and dyslipidemia are major risk factors for cardiovascular disease (CVD). In 2012, over 270 million patients (25.2%) in China were hypertensive and 40.4% was dyslipidemic. The majority of these patients rely on statins for the prevention of cardiovascular disease. However, certain types of statins (e.g., atorvastatin), compared to others (e.g., pitavastatin), may be associated with unfavorable effects on glucose metabolism. This leads to concerns when prescribing statins to patients who also have a predisposition to glucose metabolic disorders (i.e., prediabetes). Thus, this study aims to investigate the effect of pitavastatin, compared to atorvastatin, on glucose metabolism, as measured by hemoglobin A1c (HbA1c), in Chinese prediabetics with hypertension and dyslipidemias.

Methods

The China hemoglobin A1c Metabolism Protection Union Study (CAMPUS) is a multi-center, prospective, open-label, 12-month, two-arm parallel group, and non-inferiority randomized controlled trial (RCT). A total of 396 prediabetics with hypertension and dyslipidemias will be randomly assigned 1:1 to either pitavastatin 2 mg/day or atorvastatin 20 mg/day, and followed for 12 months (follow-up visits at 1, 3, 6, and 12 months) for HbA1c levels, as well as other measures of glucose metabolism, serum lipid levels, blood pressure control, measures of inflammation, vascular endothelial function, carotid atherosclerosis, and hypertension-related left ventricular hypertrophy. If the results of low-density lipoprotein cholesterol (LDL-C) levels in month 3 after treatment initiation do not meet individual target, drug dose for the participant would be doubled.

Discussion

CAMPUS will be the first RCT to investigate the effect of pitavastatin, compared to atorvastatin, on glucose metabolism in Chinese prediabetics with hypertension and dyslipidemias. Further, this study might eventually provide information to design a clinical strategy, and facilitate the improvement of primary prevention in patients at risk for diabetes and CVD.

Trial Registration

ClinicalTrials.gov number: NCT03532620. Registered 22 May 2018

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Abbreviations

CAMPUS:

China hemoglobin A1C Metabolism Protection Union Study

CVD:

cardiovascular disease HbA1c: hemoglobin A1c

LDL-C:

low-density lipoprotein cholesterol

RCT:

randomized controlled trial

HMG-CoA:

β-hydroxy-β-methylglutaryl-coenzyme A

TC:

total cholesterol

VLDL-C:

very-low-density lipoprotein cholesterol

TG:

triglycerides

Non-HDL-C:

non-high-density lipoprotein cholesterol

BP:

blood pressure

CRP:

C-reactive protein

DM:

diabetes mellitus

FBG:

fasting blood glucose

IFG:

impaired fasting glucose

ALT:

alanine aminotransferase

ASCVD:

arteriosclerotic cardiovascular disease

FPG:

fasting plasma glucose

PG:

plasma glucose

OGTT:

oral glucose tolerance test

baPWV:

brachial-ankle pulse wave velocity

IL-6:

interleukin-6

TNF-α:

tumor necrosis factor-α

LVMI:

left ventricular mass index

CIMT:

carotid intima-media thickness

IGT:

impaired glucose tolerance

BMI:

body mass index

AST:

aspartate aminotransferase

CK:

creatine kinase

CRFs:

case report forms

SAEs:

serious adverse events

ECGs:

electrocardiograms

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Acknowledgements

We would like to show our greatest gratitude to Mr. Shengyuan Luo, a brilliant and responsible scholar, who has helped review the manuscript and improve the language for clarity.

Funding

The study is an investigator-initiated study supported by an unrestricted grant from the First Affiliated Hospital, Sun Yat-sen University.

Author information

Authors and Affiliations

  1. Department of Hypertension and Cardiovascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Jianning Zhang, Yijia Shao & Jun Tao

  2. School of Public Health, Sun Yat-sen University, Guangzhou, China

    Yin Liu

Authors
  1. Jianning Zhang
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  2. Yijia Shao
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  3. Yin Liu
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  4. Jun Tao
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Contributions

JT conceived of the study. JT, JZH, and YSH initiated the study design. JZH helped with implementation, prepared the manuscript, and was a major contributor in writing the manuscript. JT revised the manuscript. JT is grant holder. YL provided statistical expertise in clinical trial design and will conduct the primary statistical analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jun Tao.

Ethics declarations

Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

This study has been approved by the Hospital/University Ethics Committee (Clinical Research Ethics Committee at the First Affiliated Hospital of Sun Yat-sen University, Via Zhongshan 2nd road no.58, Guangzhou, China) and is compliant with the Declaration of Helsinki (1964) and its amendments.

Informed consent is required for all enrollees in CAMPUS. Informed consent will be obtained by trained CAMPUS physicians, who will provide detailed explanations about CAMPUS to the participants. The participants are informed that participation in CAMPUS is voluntary, and withdrawal from the trial will not result in loss of benefit or differential treatment outside the trial. The participants will be asked questions to test their understanding about the trial and will be given adequate time to decide if they wished to participate.

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Zhang, J., Shao, Y., Liu, Y. et al. A Multi-Center, Open-Label, Two-Arm Parallel Group Non-inferiority Randomized Controlled Trial Evaluating the Effect of Pitavastatin, Compared to Atorvastatin, on Glucose Metabolism in Prediabetics with Hypertension and Dyslipidemia: Rationale and Design for the China Hemoglobin A1c Metabolism Protection Union Study (CAMPUS). Cardiovasc Drugs Ther 32, 581–589 (2018). https://doi.org/10.1007/s10557-018-6826-6

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