Essais cliniques institutionnels : quel monitoring ?

Objectif. Les promoteurs assument la responsabilité de la qualité des essais cliniques. Ces méthodes d’assurance qualité doivent être les plus efficaces possible, et avoir un coût maîtrisé. Nous voulions décrire les erreurs les plus fréquentes, à partir de la littérature, leur impact sur les résultats, et proposer les stratégies de monitoring les plus efficientes. Résultats. Les défauts rencontrés concernent la conception, les procédures, la gestion des données et l’analyse. L’impact sur les résultats est presque toujours une surestimation de l’effet traitement. Aucune méthode de monitoring n’ayant été démontrée supérieure, un monitoring économe, ciblé sur les risques d’erreurs, avec des méthodes diversifiées est préconisé. Conclusions. La qualité d’un essai clinique réside d’abord dans la qualité de sa conception. La conduite doit permettre d’assurer une qualité maximale sur les points essentiels, grâce à une analyse des risques d’erreur et à l’utilisation extensive de l’analyse de données recueillies

Effect and Safety of Morphine Use in Acute Anterior ST‐Segment Elevation Myocardial Infarction

International audienceBackground: Morphine is commonly used to treat chest pain during myocardial infarction, but its effect on cardiovascular outcome has never been directly evaluated. The aim of this study was to examine the effect and safety of morphine in patients with acute anterior ST‐segment elevation myocardial infarction followed up for 1 year.Methods and Results: We used the database of the CIRCUS (Does Cyclosporine Improve Outcome in ST Elevation Myocardial Infarction Patients) trial, which included 969 patients with anterior ST‐segment elevation myocardial infarction, admitted for primary percutaneous coronary intervention. Two groups were defined according to use of morphine preceding coronary angiography. The composite primary outcome was the combined incidence of major adverse cardiovascular events, including cardiovascular death, heart failure, cardiogenic shock, myocardial infarction, unstable angina, and stroke during 1 year. A total of 554 (57.1%) patients received morphine at first medical contact. Both groups, with and without morphine treatment, were comparable with respect to demographic and periprocedural characteristics. There was no significant difference in major adverse cardiovascular events between patients who received morphine compared with those who did not (26.2% versus 22.0%, respectively; P=0.15). The all‐cause mortality was 5.3% in the morphine group versus 5.8% in the no‐morphine group (P=0.89). There was no difference between groups in infarct size as assessed by the creatine kinase peak after primary percutaneous coronary intervention (4023±118 versus 3903±149 IU/L; P=0.52).Conclusions: In anterior ST‐segment elevation myocardial infarction patients treated by primary percutaneous coronary intervention, morphine was used in half of patients during initial management and was not associated with a significant increase in major adverse cardiovascular events at 1 year

Life-threatening arrhythmias in anterior ST-segment elevation myocardial infarction patients treated by percutaneous coronary intervention: adverse impact of morphine

International audienceAims: Important controversies remain concerning the determinants of life-threatening arrhythmias during ST-segment elevation myocardial infarction (STEMI) and their impact on late adverse events. This study sought to investigate which factors might facilitate ventricular tachycardia (VT) and ventricular fibrillation (VF), in a homogeneous population of anterior STEMI patients defined by abrupt left anterior descending coronary artery (LAD) occlusion and no collateral flow.Methods and results: The 967 patients, who entered into the CIRCUS (Does Cyclosporine ImpRove Clinical oUtcome in ST elevation myocardial infarction patients) study, were assessed for further analysis. Acute VT/VF was defined as VT (run of tachycardia >30 s either self-terminated or requiring electrical/pharmacological cardioversion) or VF documented by electrocardiogram or cardiac monitoring, during transportation to the cathlab or initial hospitalization. VT/VF was documented in 136 patients (14.1%). Patients with VT/VF were younger and had shorter time from symptom onset to hospital arrival. Site of LAD occlusion, thrombus burden, area at risk, pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow, and ST-segment resolution were similar to that of patients without VT/VF. There was no impact of VT/VF on left ventricular remodelling or clinical outcomes. By multivariate analysis, the use of morphine (odds ratio 1.71; 95% confidence interval (1.13-2.60); P = 0.012) was the sole independent predictor of VT/VF occurrence.Conclusions: In STEMI patients with LAD occlusion, our findings support the view that morphine could favour severe ventricular arrhythmias

Predictive value of early cardiac magnetic resonance imaging functional and geometric indexes for adverse left ventricular remodelling in patients with anterior ST-segment elevation myocardial infarction: A report from the CIRCUS study

International audienc

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial)

Abstract: Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow <= 1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1: 1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in theminutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. Results Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. Conclusions The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up