Clinical trial NCT03007524: Early Vascular Healing in Acute Coronary Syndrome Patients With Different Doses of Rosuvastatin
Official title: A Randomized Comparison of Low-dose Versus High-dose Rosuvastatin on Optical Coherence Tomography Based Early Vascular Healing for Patients With Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: rosuvastatin
optical coherence tomography
acute coronary syndrome
Lead sponsor: Nanjing First Hospital, Nanjing Medical University
Sponsor class: OTHER
First posted: 2017-01-02
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized trial comparing different doses of rosuvastatin in patients with acute coronary syndrome post drug-eluting stents implantation. Through the study, the investigators aim to evaluate the effects of high dose rosuvastatin calcium on "target vessel" endothelialization and "non-target vessel" plaque stability. Moreover, the investigators may provide mechanically evidence of clinical application of high dose rosuvastatin in patients with acute coronary syndrome.

Detailed description: This is a prospective, multicenter, randomized controlled clinical trial comparing different doses of rosuvastatin in patients with acute coronary syndrome post drug-eluting stents implantation. In total, the investigators plan to recruit 80 patients with acute coronary syndrome (but no acute ST-segment elevation myocardial infarction) participating in the study. After signing informed consent form, the patients will be randomly assigned into high dose rosuvastatin and low dose rosuvastatin groups (40 cases in each group) by a computer generated random sequence table on a ratio of 1:1. Patients in the high-dose group will be prescribed rosuvastatin calcium of 20mg/d at least 6 months post index procedure, while patients in low dose group will have rosuvastatin calcium of 10mg/d, also at least 6 months. Additionally, all patients will receive dual antiplatelet therapy (oral aspirin 100mg qd, clopidogrel 75mg qd or ticagrelor 90 mg bid). Clinical follow up (telephone or out-patient follow-up) will be scheduled at 30 days, 6 months, 1 year, 2 years and 3 years. Optical coherence tomography examinations will be performed at 6 months. Neointimal hyperplasia, stent strut coverage and thin cap fibroatheroma are primary observational parameters. Multi-slices CT are optional pre-/post-procedure and at 3 years follow-up. All clinical data will be collected and managed by statistical center, clinical endpoint adjudication committee. All imaging modalities data will be collected and analysed by an independent imaging core laboratory.

Eligibility criteria: Inclusion Criteria:

1. 18 to 75 years male or non-pregnant female;
2. Clinical evidence of unstable angina or non ST segment elevation myocardial infarction (NSTEMI);
3. The patient has up to two de novo native coronary lesions in different epicardial vessels;
4. Target lesion diameter stenosis ≧70%(visually estimated);
5. Each target lesion must be treated with maximal 2 stents (except the bailout stenting);
6. Low density lipoprotein (LDL) higher than 100mg/dL or lower than 100mg/dL but have taken statin drugs less than 1 month before enrolled;
7. Patient is an acceptable candidate for emergency coronary artery bypass grafting;
8. The patient is able to understand the aim of this study, provide voluntarily written informed content and agree to the follow-up visits including angiographic、multislice spiral computed tomography(MSCT) and optical coherence tomography(OCT) examinations;

Exclusion Criteria:

1. Any acute myocardial infarction within the past 1 months; myocardial enzyme not back to normal after myocardial infarction;
2. Chronic total occlusive lesion, severe left main coronary artery disease, orifice lesion, 3-vessel disease, bifurcation lesions (with side branch diameter greater than 2 mm, orifice diameter stenosis greater than or equal to 50%, or side branch need to be protected by guidewire or balloon), OCT imaging is not suitable for the lesion site or OCT imaging is incomplete, Target lesion located in previous venous or arterial bypass grafts, Target lesion has visible thrombus, intercurrent infection, or other inflammatory diseases.;
3. Heavily calcified lesions, severely tortuous lesions, lesions cannot be well pre-dilated and/or unsuitable of the stent crossover/expansion;
4. In-stent restenosis lesions;
5. Prior percutaneous coronary intervention(PCI) within the past 1 year; plan to possibly have re-intervention within 1 year post index-procedure; previous PCI more than 1 year at the target vessel;
6. Instability of hemodynamic or respiratory cycle, such as cardiogenic shock, Heart failure with severe symptoms (over New York Heart Association III(NYHA III)) or left ventricular ejection fraction less than 40% (UCG or left ventricle radiography);
7. Known renal insufficiency (e.g, Glomerular filtration rate(eGFR) \<60 ml/kg/m2 or serum creatinine level of \>2.5 mg/dL, or subject on dialysis);
8. History of bleeding tendency, active peptic ulcer and cerebral hemorrhage or retinal hemorrhage, and a half years history of stroke, antiplatelet agents and anticoagulants therapy contraindications to anticoagulation in patients;
9. Patients have been used statins and other lipid-lowering drug treatment more than 1 month before enrolled,patients allergy to rosuvastatin or use rosuvastatin with contraindications,patients allergy to aspirin, clopidogrel or ticagrelor, heparin, contrast agent, polymer, zotarolimus and metal;
10. Life expectancy \<6 months;
11. Currently participating in an investigational drug or another device study that has not completed the primary endpoint;
12. Unable or unwilling to comply with the protocol or not expected to complete the study period, including its follow-up requirements;
13. The patient is a recipient of a heart transplant;
14. Unstable arrhythmia, such as high risk ventricular contraction, ventricular arrhythmia;
15. With the need of chemotherapy in 30 days due to malignancy;
16. Patients with immune suppression or autoimmune diseases planning to have or currently receive immunosuppressive therapy;
17. Patients planning to have or currently receive long-term anticoagulation therapy;
18. Patients may receive surgery within 6 months post index-procedure in which needs to stop aspirin, clopidogrel or ticagrelor;
19. Neutropenia (\<1000 neutrophils/mm3), Thrombocytopenia (\<100,000 platelets/mm3), Confirmed or suspected diagnosis of liver diseases;
20. Patients with diffuse peripheral vascular disease which precludes 6 French unit(6F) sheath insertion;

Primary outcomes:
measure: Proportion of covered struts
timeFrame: 6 months
Secondary outcomes:
measure: Mean/Minimal stent diameter
timeFrame: 6 months
measure: Mean/Minimal stent area
timeFrame: 6 months
measure: Mean/Minimal stent volume
timeFrame: 6 months
measure: Mean/Minimal lumen diameter
timeFrame: 6 months
measure: Mean/Minimal lumen area
timeFrame: 6 months
measure: Mean/Minimal lumen volume
timeFrame: 6 months
measure: Mean/Minimal vessel diameter
timeFrame: 6 months
measure: Mean/Minimal vessel area
timeFrame: 6 months
measure: Mean/Minimal vessel volume
timeFrame: 6 months
measure: Mean/Minimal thickness of stent strut coverage
timeFrame: 6 months
measure: thin cap fibroatheroma(TCFA)
timeFrame: 6 months
measure: Cap thickness of thin cap fibroatheroma(TCFA)
timeFrame: 6 months
measure: Neointimal Hyperplasia area
timeFrame: 6 months
measure: Neointimal Hyperplasia volume
timeFrame: 6 months
measure: Incomplete strut apposition
timeFrame: 6 months
measure: Device-oriented composite endpoint
timeFrame: 1 and 6 months, 1, 2, 3 years
measure: Cardiac death
timeFrame: 1 and 6 months, 1, 2, 3 years
measure: Non-fatal myocardial infarction
timeFrame: 1 and 6 months, 1, 2, 3 years
measure: All revascularization
timeFrame: 1 and 6 months, 1, 2, 3 years
measure: target lesion revascularization
timeFrame: 1 and 6 months, 1, 2, 3 years
measure: target vessel revascularization
timeFrame: 1 and 6 months, 1, 2, 3 years
measure: stent thrombosis
timeFrame: 1 and 6 months, 1, 2, 3 years
Other outcomes:
measure: Lipid levels
timeFrame: Baseline，6 months
measure: Biological index
timeFrame: Baseline，6 months
Locations:
city: Nanjing
country: China
facility: Nanjing First Hospital, Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Yao-Jun Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital
name: Ze-Ning Jin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Fei Ye, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Song Lin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fu Wai Hospital, Beijing, China
name: Bo Xu, MSc
role: STUDY_DIRECTOR
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