Clinical trial NCT02077257: LDL-C Lowering Efficacy and Safety of Rosuvastatin 20 mg/Day to10 mg/Day in Chinese ACS(Acute Coronary Syndrome) Patients
Official title: A 12-Week, Randomized, Open-Label, Multicenter Study Exploring Low-Density Lipoprotein Cholesterol Lowering Efficacy and Safety of Rosuvastatin 20 mg/Day Compared to10 mg/Day in Chinese Patients With Acute Coronary Syndromes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Lead sponsor: Committee of Cardio-Cerebral-Vascular Diseases of GSC
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2014-03-04
Enrollment: 1060
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 12-week, randomized, open-label,,multicenter, Phase IV study exploring LDL-C lowering efficacy of Rosuvastatin 20 mg/d compared to 10 mg/day Chinese ACS patients.The Randomized Treatment Period is preceded by a 24hours Screening Period. The study flow chart (Figure 1) depicts the 2 periods which comprise the study. These periods are described as follows:

1. Screening Period (Day -1 through Day 1) This period consists of Visits 1 and 2. Subjects entering the Screening Period are required to meet the inclusion criteria. All subjects will be instructed to follow the current TLC(therapeutic lifestyle change)dietary guidelines for the duration of the trial.
2. 12-week Randomized Treatment Period (Day 1 through Week 12) This period consists of Visits 2, 3, 4, and 5. Eligible subjects will be randomized at Visit 2 to each treatment group: Rosuvastatin 20 mg orRosuvastatin10 mg. Treatment will be administered once daily for 12 weeks.

A total of 450valid subjects in each of the Rosuvastatin arms are required, in order to test the hypothesis of superiority for comparison of LDL-C levels between Rosuvastatin20 mg and Rosuvastatin10 mg(see Section 6.1 for more details).

The Study visit schedule(Table 2) indicates the number and timing of the planned visits. The visit schedule must be within time window. At the final visit, it is the responsibility of the investigator to ensure the subject is offered an selected appropriate type of lipid-lowering therapy.

Scheduled Visit3,4,5 will have a visit window of ±2 days. Subjects who attend a clinic visit without fasting (at least 12 hours) should be asked to return within 2 days for another clinic visit after fasting for at least 12 hours.


Eligibility criteria: Inclusion Criteria:

* 18-80 year old males and non-child-bearing period females.
* Clinical diagnosed with acute coronary syndrome including NSTE-ACS ,MI and STEMI.
* Patients with STEMI((ST segment elevation myocardial infarction) and NSTEMI(non-ST segment elevation myocardial infarction) will be recruited within 48 hours of symptom onset.
* The LDL-C≥70mg/dL one week before randomization.
* The TG\<500mg/dL one week before randomization.
* No cholesterol-lowering drugs (including lipid lowering dietary supplements, antioxidants, or food additives) during 4 weeks before randomization.
* Sign the ICF(inform consent form)

Exclusion Criteria:

* Acute pulmonary edema, severe congestive heart failure,
* acute moderate mitral regurgitation, acute ventricular septal perforation,
* severe arrhythmia (ventricular fibrillation, sustained ventricular tachycardia, complete heart block), sepsis, acute pericarditis,
* any evidence of systemic or pulmonary embolus within the preceding 4 weeks.
* Coronary artery bypass graft within the preceding 3 months; percutaneous coronary intervention within the preceding 6 months.
* A history of hypersensitivity of statins and other severe complication.
* child-bearing women
* hypothyroidism,
* active liver disease or dysfunction including agnogenic serum transaminase sustained elevation or higher than 3 times ULN(upper limit of normal)
* severe anemia (hemoglobin,hematocrit \< 28%),
* Patients with myopathy or serum creatine kinase \> 3 times the upper limit of normal not caused by myocardial injury.
* A history of psychiatric disorders
* A history of jejunoileal bypass or gastric bypass surgery
* Currently take steroids therapy
* Currently take phenytoin sodium,phenobarbital,carbamazepine (which may primary efficacy endpoint)
* Diagnosed with malignant within 5 years
* Severe renal function damage (creatinine clearance rate\<30 ml/min)
* Concurrent use ciclosporin

Primary outcomes:
measure: LDL-C absolute value and percent change from baseline
timeFrame: 12 weeks
Secondary outcomes:
measure: blood lipid goal achievement rate(LDL-C <70 mg/dl or 50% reduction)
timeFrame: 6 week
measure: blood lipid goal achievement rate(LDL-C <70 mg/dl or 50% reduction)
timeFrame: 12 weeks
measure: Percent change from baseline in TC,HDL-C, TG, nonHDL-C (non HDL-C = [TC-HDL-C]), ApoA-I, ApoB, LDL-C/HDL-C, TC/HDL-C, non HDL-C/HDL-C, ApoB/ApoA-I and LDL-C
timeFrame: 6weeks
measure: Percent change from baseline in TC, HDL-C, TG, nonHDL-C (non HDL-C = [TC-HDL-C]), ApoA-I, ApoB, LDL-C/HDL-C, TC/HDL-C, non HDL-C/HDL-C, ApoB/ApoA-I and LDL-C
timeFrame: 12 weeks
measure: Percent change from baseline in the level of hsCRP(high-sensitivity C-reactive protein), an inflammatory marker
timeFrame: 6 weeks
measure: Percent change from baseline in the level of hsCRP, an inflammatory marker,
timeFrame: 12 weeks
measure: incidence and severity of adverse events
timeFrame: 12 weeks
measure: abnormal physical examination findings
timeFrame: 12 weeks
measure: abnormal laboratory values
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital
state: Beijing
Study officials:
affiliation: Beijing university People's hospital
name: Dayi Hu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital
name: Changsheng Ma, Doctor
role: PRINCIPAL_INVESTIGATOR
References: