Clinical trial NCT02546323: A phase3 Study Measuring the Effect of Rosuvastatin 20 mg on Carotid Intima-Media Thickness in Chinese Subjects With Subclinical Atherosclerosis
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Parallel Group Phase 3 Study Measuring the Effect of Rosuvastatin 20 mg on Carotid Intima-Media Thickness in Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atherosclerosis
Keywords: Rosuvastatin 20 mg treatment, Carotid Intima-Media Thickness, Chinese subjects, Subclinical atherosclerosis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-09-10
Enrollment: 543
Sex: ALL
Minimum age (years): 45
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effects of of rosuvastatin 20 mg compared to placebo for treating Chinese patients with subclinical atherosclerosis.

Detailed description: This study is a randomized, double-blind, placebo-controlled, multicenter parallel group study assessing the effects of rosuvastatin 20 mg treatment for 104 weeks on the change in intimamedia thickness (IMT) of the common carotid artery (CCA), carotid bulb, and internal carotid artery (ICA) in adult Chinese subjects with subclinical atherosclerosis.

Eligibility criteria: Inclusion Criteria:

* Provision of informed consent prior to any study-specific procedures
* Male aged ≥45 and \<70 years or female aged ≥55 and \<70 years
* Subjects with only hypertension (as defined blood pressure ≥140/90 mmHg or on antihypertensive treatment) and age as CVD risk factors and subjects without hypertension who have 3 or more other risk factors (including age) must have "Fasting LDL C of ≥120 mg/dL (3.1 mmol/L) and \<160 mg/dL (4.1mmol/L)"; Subjects without hypertension who have fewer than 3 other risk factors (including age) must have "Fasting LDL-C of ≥120 mg/dL (3.1 mmol/L) and \<190 mg/dL (4.9 mmol/L)"
* Triglycerides \<500 mg/dL (5.65 mmol/L) at Visit 1
* HDL-C levels ≤60 mg/dL (1.6 mmol/L) at Visit 1
* Maximum IMT ≥1.2 mm and \<3.5 mm at any location in the carotid ultrasound scans conducted at both Visit 2 and Visit 3
* Willing to follow all study procedures including study visits, fasting blood draws, and compliance with study treatment regimen

Exclusion Criteria:

* Use of pharmacologic lipid-lowering medications (eg, statins, fibrate derivatives,bile acid binding resins, niacin, or its analogues at doses \>400 mg or prescribed Chinese traditional drugs), including cholesterol-absorption inhibitors (CAIs), and CAI/statin combination, within 12 months prior to Visit 1
* Current or recent (within 2 weeks of Visit 1) use of supplements known to alter lipid metabolism (eg, soluble fibers \[including \>2 teaspoons Metamucil® or psyllium-containing supplement per day\] or other dietary fiber supplements, marine oils, sterol/stanol products, or other supplement determined at the discretion of the investigator)
* History of hypersensitivity reactions to other HMG-CoA reductase inhibitors
* Pregnant women, women who are breast-feeding, and women of childbearing potential who are not using chemical or mechanical contraception or who have a positive serum pregnancy test
* Clinical evidence of coronary artery disease (CAD) or any other atherosclerotic disease such as angina, MI, transient ischemic attack, symptomatic CAD, cerebrovascular accident, percutaneous coronary intervention, coronary artery bypass graft, peripheral arterial disease, abdominal aortic aneurysm
* History of cancer (other than basal cell carcinoma) in the past 2 years
* Uncontrolled hypertension defined as either a mean resting diastolic blood pressure of ≥110 mmHg or a resting systolic blood pressure of ≥180 mmHg recorded at any time during the screening period
* History of diabetes mellitus or current diabetes mellitus
* Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH) \>1.5 times the upper limit of normal (ULN) at Visit 1 or subjects whose thyroid replacement therapy was initiated within the last 3 months
* History of heterozygous or homozygous familial hypercholesterolemia or known hyperlipoproteinemia Types I, III, IV, or V (familial dysbetalipoproteinemia)
* Use of the disallowed concomitant medications within 12 months prior to Visit 1
* History of alcohol and/or drug abuse within the past 5 years
* Active liver disease or hepatic dysfunction as defined by elevations of ≥1.5 x ULN at Visit 1 in any of the following liver function tests: ALT, AST or bilirubin
* Serum creatine kinase (CK) \>3 x ULN at Visit 1
* Serum creatinine \>2.0 mg/dL (177 mmol/L) recorded during the screening period
* Participation in another investigational drug study, and having ingested investigational drug ≤4 weeks before enrollment in the screening period
* Previous randomization in the present study
* History of a significant medical or psychological condition that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study
* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

Primary outcomes:
measure: Annualized Rate of Change in Mean of the Maximum (MeanMax) CIMT Measurements From Each of the 12 Carotid Artery Sites Based on All Scans Performed During the 104-Week Study Period
timeFrame: From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).
Secondary outcomes:
measure: Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left CCA
timeFrame: From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).
measure: Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left Carotid Bulb
timeFrame: From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).
measure: Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left ICA
timeFrame: From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).
measure: Annualized Rate of Change in the Mean of the Mean (MeanMean) CIMT of the Near and Far Walls of the Right and Left CCA
timeFrame: From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).
measure: Percent Change From Baseline in Lipid, Lipoprotein and Apolipoprotein Values at Final Visit: Last Observation Carried Forward (LOCF)
timeFrame: From baseline (Week 0) to end-of-study (Week 104).
measure: Percent Change From Baseline in Lipid and Lipoprotein Values at Final Visit: Time Weighted Average
timeFrame: From baseline (Week 0) to end-of-study (Week 104).
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Bengbu
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqin
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Haerbin
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xian
country: China
facility: Research Site
Study officials:
affiliation: Beijing Tian Tan Hospital, Capital Medical University
name: Yongjun Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: Yundai Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zheng H, Li H, Wang Y, Li Z, Hu B, Li X, Fu L, Hu H, Nie Z, Zhao B, Wei D, Karlson BW, Bots ML, Meng X, Chen Y, Wang Y; METEOR-China Investigators. Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study. Stroke. 2022 Oct;53(10):3004-3013. doi: 10.1161/STROKEAHA.120.031877. Epub 2022 Aug 26.
citation: Wang Y, Wang A, Li H, Li Z, Hu B, Li X, Zheng H, Fu L, Hu H, Nie Z, Qin Y, Zhao B, Wei D, Karlson BW, Bots ML, Chen Y, Wang Y. Measuring effects on intima-media thickness: an evaluation of rosuvastatin in Chinese subjects with subclinical atherosclerosis-design, rationale, and methodology of the METEOR-China study. Trials. 2020 Nov 11;21(1):921. doi: 10.1186/s13063-020-04741-0.