ACE究將指導(dǎo)心血管疾病全面防治的新策略

1、professor rury holmanuniversity of oxford, ukprofessor chang yu panprofessor da yi huchinese pla general hospitaluniversity of pekingchinachinarationale for ace trial accumulating evidence suggests there is a close association between “prediabetes” and cardiovascular disease (cvd) treating conventio

2、nal risk factors in type 2 diabetes does not reduce cvd risk to the same level as in a non-diabetic population post prandial hyperglycaemia may explain the excess risk seen in diabetes and “prediabetes” acarbose has been reported* to reduce cvd risk in individuals with “prediabetes”, but its impact

3、on new cvd events in individuals with “prediabetes” and existing cvd and is unknown* chiasson jl et al. jama 2003; 290(4): 486-94ace trial managementcoordinating centre diabetes trials unit, university of oxfordace chinese project office oxford university (beijing) science & technology limitedfu

4、nding & study medication bayer healthcare china & bayer schering pharmastudy designdouble-blind, multi-centre, randomised, controlled, clinical outcome trial comparing acarbose versus placebo investigator designed and led academic trialindependent data collection, analysis and reportingcondu

5、cted in mainland china and hong kong7,500 patients in 150 cardiovascular centresminimum patient follow up four yearsevent driven (904 adjudicated primary events)rury holmanuk diabetologist(chair)dayi huchina cardiologist(co-chair)changyu panchinadiabetologist(co-chair)jialun chenchinadiabetologist(h

6、onoured adviser)juliana chanhong kongdiabetologistjean-louis chiassoncanadadiabetologistjunbo gechinacardiologisthertzel gersteincanadadiabetologistjohn mcmurrayukcardiologistlars rydnswedencardiologistmichal tenderapoland cardiologistjaakko tuomilehtofinlandepidemiologistwenying yangchinadiabetolog

7、istjoanne keenanukdtu project managerdieter neusergermanybayer project managerthorsten petruschkegermanybayer project managerace steering committeemajor inclusion criteriaconfirmed cardiovascular disease (cvd)- history of myocardial infarction- previous unstable angina- current stable anginaimpaired

8、 glucose tolerance (igt) on an oral glucose tolerance test with:- fasting plasma glucose 3x uln)severe renal impairment(egfr 30 ml/min/1.73m2)gastrointestinal problems or alpha glucosidase inhibitor intolerancepregnancy or possibility of pregnancythought by the investigator to be unsuitableace prima

9、ry endpointcomposite “hard” cvd endpointdefined as the time to the first occurrence after randomisation of any of: cardiovascular death resuscitated cardiac arrest non-fatal myocardial infarction non-fatal strokean endpoint adjudication committee, masked to therapy allocation, will review all potent

10、ial cvd endpoints independently.new-onset type 2 diabetes, confirmed by two successive diagnostic plasma glucose values- fpg 7.0 mmol/land/or- 2hpg 11.1 mmol/lace secondary endpoint all cause mortality extended cvd endpoint of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial i

11、nfarction, fatal or non-fatal stroke and hospitalisation for heart failure or for unstable angina.- each component will also be analysed individually evidence of non-alcoholic fatty liver disease (nafld) as judged by alt changes development of impaired renal function (egfr 60 ml/minute/1.73 m2) or d

12、oubling of baseline creatinine health economic evaluationother secondary outcomessample size estimationassumes a primary event rate of 3.5% per year a 20% relative reduction compared with placebo an 18 month accrual period alpha of 5%for 90% power the study requires 7,268 patients with a minimum of

13、904 adjudicated primary events a total of 7,500 patients will be recruited to allow for an overall 3% loss-to-follow updouble blind interventionin addition to optimised cvd therapy:randomised to:-acarbose, 50 mg three times a dayor-matching placebo, three times a daytablets to be taken with mealsuse

14、 start low, go slow dose titrationace study flow chartminimum of 904 adjudicated primary events required7,500cvdor acsoptimisation of cardiovascular therapycvd therapy will be optimised during the four-week, single-blind, placebo run-in period to ensure it conforms with international guidelines for

15、treating patients with established cvdthat is: antiplatelet therapy, unless contraindicated or not tolerated a statin, unless contraindicated or not tolerated ace inhibitor, beta-blocker, and/or antihypertensive therapy if considered indicated by the investigatorsafetythe ace trial will be conducted

16、 to ich-gcp standardsliver function will be monitored annuallyserious unexpected suspected adverse reactions (susars) will undergo expedited reportingan independent data safety monitoring board (dsmb) will review unblinded safety data at least six-monthlythe ace trial is enrolling 150 cardiovascular

17、 centres in mainland china and hong kingeach centre is expected to recruit approximately 50 patients (minimum of 35 patients)recruitment is competitive and will close when 7,500 patients have been randomisedthe ace trial results are expected in 2014scheduleclinical centre requirementsqualified resea

18、rch staff and appropriate facilities to safely and properly conduct the trial in accordance with ich gcp guidelinesproven clinical trial experience or willingness to acquire the necessary skillsaccess to a sufficient eligible patients to ensure around 50 can be enrolled and kept in the trial for a minimum followed up p