NCT02546323

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

Completed Phase 3 Results posted Last updated 11 December 2019

What this trial tests

Phase 3 trial testing Rosuvastatin in Atherosclerosis in 543 participants. Completed in 29 January 2019.

Timeline

17 September 2015

Primary endpoint
29 January 2019

29 January 2019

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	543
Start date	17 September 2015
Primary completion	29 January 2019
Estimated completion	29 January 2019
Sites	24 locations across China

Drugs / interventions tested

• Rosuvastatin (rosuvastatin) — full drug profile →
• Placebo

Conditions studied

• Atherosclerosis — all drugs for Atherosclerosis →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 45 to 69, any sex, with Atherosclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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

Group	Value	95% CI
Rosuvastatin 20 mg	0.0038	± 0.00312
Placebo	0.0142	± 0.00317

Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left CCA Secondary · From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

CIMT measurements were made from ultrasound images of the near and far walls of the right and left CCA. 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. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that es

Group	Value	95% CI
Rosuvastatin 20 mg	-0.0031	± 0.00310
Placebo	0.0079	± 0.00315

Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left Carotid Bulb Secondary · From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

CIMT measurements were made from ultrasound images of the near and far walls of the right and left carotid bulb. 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. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression mode

Group	Value	95% CI
Rosuvastatin 20 mg	0.0067	± 0.00634
Placebo	0.0228	± 0.00643

Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left ICA Secondary · From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

CIMT measurements were made from ultrasound images of the near and far walls of the right and left 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. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level mixed effects regression model that estimated

Group	Value	95% CI
Rosuvastatin 20 mg	0.0077	± 0.00502
Placebo	0.0120	± 0.00511

Annualized Rate of Change in the Mean of the Mean (MeanMean) CIMT of the Near and Far Walls of the Right and Left CCA Secondary · From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

CIMT measurements were made from ultrasound images of the near and far walls of the right and left CCA. 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. The 3 images recorded at the 3 interrogation angles were measured to determine the mean of the CIMT for this segment. The annualized rate of change in the MeanMean CIMT measurements, based on all scans performed during the study, was determined using a multi-level mixed effects regression model that estimated m

Group	Value	95% CI
Rosuvastatin 20 mg	-0.0011	± 0.00191
Placebo	0.0075	± 0.00194

Percent Change From Baseline in Lipid, Lipoprotein and Apolipoprotein Values at Final Visit: Last Observation Carried Forward (LOCF) Secondary · From baseline (Week 0) to end-of-study (Week 104).

The percent change from baseline at final visit for lipid and lipoprotein measurements (low-density lipoprotein cholesterol \[LDL-C\], total cholesterol, high-density lipoprotein cholesterol \[HDL-C\], triglycerides, non-HDL-C, non-HDL-C/HDL-C ratio) and apolipoprotein measurements (apolipoprotein A-I \[ApoA-I\], apolipoprotein B \[ApoB\] and ApoB/ApoA-I ratio) was determined by analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline value as a covariate. In the evaluation of change from baseline (Week 0) to the final visit at Week 104, any missing observations were imput

LDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	-26.47	± 1.700
Placebo	8.99	± 1.727

Total Cholesterol

Group	Value	95% CI
Rosuvastatin 20 mg	-20.56	± 1.010
Placebo	1.29	± 1.026

HDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	5.47	± 0.944
Placebo	0.48	± 0.959

Triglycerides

Group	Value	95% CI
Rosuvastatin 20 mg	-7.26	± 2.575
Placebo	12.38	± 2.616

Non-HDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	-27.67	± 1.344
Placebo	1.82	± 1.365

Non-HDL-C/HDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	-28.52	± 1.637
Placebo	3.23	± 1.663

ApoB

Group	Value	95% CI
Rosuvastatin 20 mg	-24.20	± 1.307
Placebo	1.91	± 1.295

ApoA-I

Group	Value	95% CI
Rosuvastatin 20 mg	3.16	± 0.784
Placebo	0.96	± 0.777

Percent Change From Baseline in Lipid and Lipoprotein Values at Final Visit: Time Weighted Average Secondary · From baseline (Week 0) to end-of-study (Week 104).

The percent change from baseline at final visit for lipid and lipoprotein measurements (LDL-C, total cholesterol, HDL-C, triglycerides, non-HDL-C, non-HDL-C/HDL-C ratio) was determined by ANCOVA with treatment as a fixed effect and baseline value as a covariate. In the evaluation of change from baseline (Week 0), the time-weighted average value was calculated as the value multiplied by the number of days since the last assessment, summed for all observations, and divided by the sum of days between all visits.

LDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	-34.89	± 1.275
Placebo	4.62	± 1.295

Total Cholesterol

Group	Value	95% CI
Rosuvastatin 20 mg	-23.98	± 0.798
Placebo	1.49	± 0.811

HDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	7.07	± 0.737
Placebo	3.41	± 0.748

Triglycerides

Group	Value	95% CI
Rosuvastatin 20 mg	-9.05	± 2.091
Placebo	9.36	± 2.124

Non-HDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	-32.59	± 1.072
Placebo	1.19	± 1.089

Non-HDL-C/HDL-C

Group	Value	95% CI
Rosuvastatin 20 mg	-34.31	± 1.288
Placebo	-0.38	± 1.308

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment Emergent Adverse Events were collected from day of first dose in Week 0 up to and including 10 days following the date of last dose of investigational product or placebo (up to Week 104).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rosuvastatin 20 mg

Serious: 38/272 (14%)

Deaths: 0/272

Placebo

Serious: 34/268 (13%)

Deaths: 1/268

Serious adverse events (71 terms)

Reaction	System	Rosuvastatin 20 mg	Placebo
Acute myocardial infarction	Cardiac disorders	—	—
Arteriosclerosis coronary artery	Cardiac disorders	—	—
Cataract	Eye disorders	—	—
Lumbar vertebral fracture	Injury, poisoning and procedural complications	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Cerebral infarction	Nervous system disorders	—	—
Angina unstable	Cardiac disorders	—	—
Arrhythmia	Cardiac disorders	—	—
Coronary artery disease	Cardiac disorders	—	—
Sinus node dysfunction	Cardiac disorders	—	—
Vertigo positional	Ear and labyrinth disorders	—	—
Goitre	Endocrine disorders	—	—
Hyperparathyroidism primary	Endocrine disorders	—	—
Thyroid mass	Endocrine disorders	—	—
Iridocyclitis	Eye disorders	—	—
Pathologic myopia	Eye disorders	—	—
Pterygium	Eye disorders	—	—
Retinal detachment	Eye disorders	—	—
Retinal vein occlusion	Eye disorders	—	—
Anal fistula	Gastrointestinal disorders	—	—
Gastritis	Gastrointestinal disorders	—	—
Haemorrhoids	Gastrointestinal disorders	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Rosuvastatin 20 mg	Placebo
Nasopharyngitis	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Blood glucose increased	Investigations	—	—
Toothache	Gastrointestinal disorders	—	—
Hypertension	Vascular disorders	—	—
Protein urine present	Investigations	—	—
Dizziness	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: Acute myocardial infarction, Arteriosclerosis coronary artery, Cataract, Lumbar vertebral fracture, Osteoarthritis, Spinal osteoarthritis, Cerebral infarction, Angina unstable.

Data from ClinicalTrials.gov NCT02546323 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.
   Zheng H, Li H, Wang Y, Li Z, et al · · 2022 · cited 30× · PMID 36017704 · DOI 10.1161/strokeaha.120.031877
2. Hydrogen Sulfide and Oxygen Homeostasis in Atherosclerosis: A Systematic Review from Molecular Biology to Therapeutic Perspectives.
   Munteanu C. · · 2023 · cited 11× · PMID 37176083 · DOI 10.3390/ijms24098376
3. Pharmacological interventions for asymptomatic carotid stenosis.
   Clezar CN, Flumignan CD, Cassola N, Nakano LC, et al · · 2023 · cited 10× · PMID 37565307 · DOI 10.1002/14651858.cd013573.pub2
4. 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.
   Wang Y, Wang A, Li H, Li Z, et al · · 2020 · cited 2× · PMID 33176842 · DOI 10.1186/s13063-020-04741-0