Title: Randomized Controlled Trial Comparing Intracoronary Administration of Adenosine or Sodium Nitroprusside to Control for Attenuation of Microvascular Obstruction During Primary Percutaneous Coronary Intervention
Funder: Department of Health (England)

Abstract: DESIGN:Randomizedcontrolledopen label trial with blinded endpoint analysis. STUDY POPULATION: Patients presenting with P-PCI at 2 major tertiary cardiac centres (Leicester and Leeds). Inclusion criteria: All patients with STEMI eligible for reperfusion by P-PCI. Non culprit disease <70% stenosis at angiography. TIMI flow 0/I. Written informed consent. Exclusion criteria: Contraindications to P-PCI MRI scanningcontrast agents or study medications. Age <18 yrs. SBP <90mmHg cardiogenic shock. Previous Q wave MI. Culprit lesion not identified or located in a by-pass graft. Stent thrombosis. Left main disease. Severe asthma. GFR<30ml/min. Pregnancy. INTERVENTIONS: All patients will be treated with bivalirudin and thrombus aspiration and will be randomly assigned with stratification for symptoms to balloon <3 hrs or >3hrs and anterior MI or not to one of the following 3 groups: 1)Standard PCI (control). 2) Distal intracoronary (IC) adenosine (300 mcg) via microcatheter (MC). 3) Distal IC SNP (500 mcg) via MC. OUTCOME MEASURES: Primary: CMR measured infarct size (IS) at 48-72 hrs post procedure. Secondary: CMR incidence and extent of MVO myocardial salvage incidence of haemorrhage LV volumes and function in the acute stage. Overall Major Adverse Clinical Events (MACE) and its components at 6 months. Angiographic markers of MVO LV volumes and functions ECG ST resolution and cardiac enzymes. ASSESSMENT AND FOLLOW-UP: Myocardial reperfusion will be assessed using 3T CMR scanners. CMR is the gold standard technique for assessment of MVO and IS and the quantification of LV mass volumes and function. CMR analysis will be performed blinded to treatment allocation. Blood samples will be taken from the patients to assess the effect of these treatment agents on platelet activation within the coronary circulation. Follow-up for MACE will be assessed at 6 months. PROPOSED SAMPLE SIZE: to detect a 5% difference in infarct size with 90% power alpha 0.05 and two-tailed assuming expected infarct size of 20% with a SD 10% will require 86 pts/group. To allow for dropouts before CMR a total of 297 patients will be recruited. STATISTICAL ANALYSIS: Data will be examined for distribution. Groups will be compared by ANOVA and multivariate analysis will take into consideration possible confounders. Primary analysis will be by intention to treat with a secondary analysis by treatment received. For secondary endpoints time-to-event regression methods will be used to investigate potentially important predictors of MACE. Initial analyses will adopt a ‘complete case’ approach but sensitivity analyses using multiple imputation methods will also be undertaken to assess the plausibility of the ‘missing at random’ assumption.The study will be monitored by an independent data safety monitoring board. There will be an interim analysis when 5 patients have been included in each arm. Keith Abrams Prof. of Medical Statistics and NIHR Senior Investigator will oversee the statistical analysis.PROJECT TIMETABLE AND RECRUITMENT RATE: Proposed start date Jan 2011. 297 patients will be recruited in 2 high volume centresIt is estimated to take 18 months to recruit this number of patients (4 patients/week and achieved by both centres in other studies). Follow-up will end in Dec 2012.


Research activity codes: 6.3 MEDICAL DEVICES;6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR