A phase3 Study Measuring the Effect of Rosuvastatin 20 mg on Carotid Intima-Media Thickness in Chinese Subjects With Subclinical Atherosclerosis

NCT02546323 | Completed Phase 3 Results

• 1 other identifier: D3565C00003
• Study Type: interventional
• Target: 543
• Locations: 1 country
• Sites: 24

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.

Conditions

Atherosclerosis

Keywords

Rosuvastatin 20 mg treatment, Carotid Intima-Media Thickness, Chinese subjects, Subclinical atherosclerosis

Outcome Measures

Primary Outcomes (1)

• 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

  CIMT measurements were made from ultrasound images of the common carotid artery (CCA), carotid bulb and internal carotid artery (ICA). The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. Twelve carotid artery sites were scanned at each visit and the 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for a specific segment. The annualized rate of change in the MeanMax CIMT measurements from each of the 12 sites, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.

  From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

Secondary Outcomes (6)

• Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left CCA

  From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

• Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left Carotid Bulb

  From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

• Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left ICA

  From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

• Annualized Rate of Change in the Mean of the Mean (MeanMean) CIMT of the Near and Far Walls of the Right and Left CCA

  From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

• Percent Change From Baseline in Lipid, Lipoprotein and Apolipoprotein Values at Final Visit: Last Observation Carried Forward (LOCF)

  From baseline (Week 0) to end-of-study (Week 104).

Study Arms (2)

Rosuvastatin

EXPERIMENTAL

20 mg tablets, Daily oral dose

Drug: Rosuvastatin

Placebo

PLACEBO COMPARATOR

Matching placebo tablets

Drug: Placebo

Interventions

Rosuvastatin DRUG

20mg tablets, orally once daily for the duration of the 104-week treatment period

Also known as: Crestor

Rosuvastatin

Placebo DRUG

Matching placebo tablets, orally once daily for the duration of the 104-week treatment period.

Placebo

Eligibility Criteria

• Age: 45 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (24)

Research Site

Beijing, 100035, China

Location

Research Site

Beijing, 100050, China

Location

Research Site

Beijing, 100191, China

Location

Research Site

Beijing, 100853, China

Location

Research Site

Bengbu, 233060, China

Location

Research Site

Changsha, 410011, China

Location

Research Site

Chongqin, 400042, China

Location

Research Site

Guangzhou, 510080, China

Location

Research Site

Guangzhou, 510120, China

Location

Research Site

Guangzhou, 510260, China

Location

Research Site

Guangzhou, 510515, China

Location

Research Site

Guangzhou, 510630, China

Location

Research Site

Haerbin, 150001, China

Location

Research Site

Nanchang, 330006, China

Location

Research Site

Nanjing, 210009, China

Location

Research Site

Ningbo, 315010, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Shanghai, 200065, China

Location

Research Site

Shanghai, 200090, China

Location

Research Site

Shenyang, 110001, China

Location

Research Site

Tianjin, 300457, China

Location

Research Site

Wenzhou, CN-325000, China

Location

Research Site

Wuhan, 430022, China

Location

Research Site

Xi'an, 710061, China

Location

Related Publications (3)

• Clezar CN, Flumignan CD, Cassola N, Nakano LC, Trevisani VF, Flumignan RL. Pharmacological interventions for asymptomatic carotid stenosis. Cochrane Database Syst Rev. 2023 Aug 4;8(8):CD013573. doi: 10.1002/14651858.CD013573.pub2.

  PMID: 37565307 DERIVED

• 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.

  PMID: 36017704 DERIVED

• 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.

  PMID: 33176842 DERIVED

Related Links

• redacted protocol
• SAP\_redacted

MeSH Terms

Conditions

Atherosclerosis

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+1 302 885 1180

Study Officials

• Yongjun Wang, M.D.

  Beijing Tian Tan Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

• Yundai Chen, M.D.

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2015
• First Posted: September 10, 2015
• Study Start: September 17, 2015
• Primary Completion: January 29, 2019
• Study Completion: January 29, 2019
• Last Updated: December 11, 2019
• Results First Posted: December 11, 2019

Record last verified: 2019-10

Locations

CN (24)