Safety and Efficacy Study of TRO40303 for Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction
Objectives of the phase 2 prospective, multicenter, randomized, double-blind, placebo-controlled study is to assess safety and efficacy of TRO40303 administered just before balloon inflation during percutaneous coronary intervention (PCI) for limitation of infarct size in patients treated for acute myocardial infarction (AMI).
The study is being conducted in 9 centres in Sweden, Denmark, Norway and France. One hundred eighty patients will be included. It will last one month per patient and its overall duration will be 11 months.
The efficacy will be assessed by infarct size expressed as area under the curve for creatine kinase and troponin I (blood sampling at D1, D2 and D3), and also evaluated by Cardiac Magnetic Resonance.
Safety will be assessed by
- clinic evaluation,
- blood samples (hematology, biochemistry, renal and hepatic function),
- Recording and follow-up of major adverse events occurring during the first 48h after reperfusion (death, heart failure, AMI, stroke, recurrent ischemia, the need for repeat revascularization, renal or hepatic, vascular complication and bleeding).
- Recording cardiac events during one month after AMI
- Follow-up of global left ventricular function by Echocardiography at D3 and D30.
Demographic and medical history at inclusion and non-cardiac events occurring during the first 30 days will be recorded. TRO40303 plasma concentration will be assessed at 15 min, 6h, and 12h post the end of administration.
Sample size calculation assuming a reduction of 35% of the AUC for Troponin I release, for a statistical power of 85% and a probability of type I error of 0.05.
Main analysis: between-group comparisons of AUCs for serum troponin I and CK release will be performed using O'Brien's method for multiple endpoints testing.
Secondary analysis: comparisons of the CMR criteria described above will be performed using mixed model of ANCOVA.
All analyses will be performed on the Full Analysis Set and Per protocol populations.
Safety analysis: A comparison of the incidence of cumulative adverse clinical events between the groups will be performed by Fisher's exact tests.
Subjects will undergo primary PCI and receive concomitant medications according to current standard of care.
After coronary angiography is performed but just before balloon inflation is performed, patients who meet the enrollment criteria will be randomly assigned to either the control group or the TRO40303 group. Randomization is ensured by taking the treatment units in ascending and consecutive order in each strata (anterior/posterior as determined on ECG). Just before balloon inflation, ideally less than 5 minutes, and with a maximum of 15 minutes before balloon inflation and stenting, the patients in the TRO40303 group will receive an intravenous slow-bolus (35 mL/min) injection of 6 mg/kg of TRO40303 injected in peripheral IV. The patients in the control group will receive an equivalent volume of the placebo. Patients will be hospitalized for as long as there is a medical indication. CMR and echocardiography will accordingly be conducted as in/out patient between day 3 (ideally) and 5. A follow-up visit will be conducted one month after PCI.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Phase II, Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of TRO40303 for Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction|
- Infarct size expressed as area under the curve for Creatine kinase and Troponin I [ Time Frame: Blood samples will be collected at admission and every 6 hours until 72h ] [ Designated as safety issue: No ]
- Infarct size evaluated by Cardiac Magnetic Resonance [ Time Frame: A cardiac magnetic resonance between day 3 and Day 5 after balloon inflation ] [ Designated as safety issue: No ]
|Study Start Date:||October 2011|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
single dose just before balloon inflation by slow bolus (35ml/min, peripheral IV)
6 mg/kg, peripheral IV, single dose just before balloon inflation, slow bolus (35ml/min)
|Aarhus University Hospital|
|Aalborg, Denmark, 9000|
|Odense University Hospital|
|Odense, Denmark, 5000|
|Hôpital Henri Mondor|
|Créteil, France, 94010|
|Hôpital Nord Marseille|
|Hôpital La Timone|
|Marseille, France, 13005|
|Hôpital Européen Georges Pompidou|
|Paris, France, 75015|
|Haukeland University Hospital|
|Bergen, Norway, NO-5021|
|Oslo University Hospital|
|Oslo, Norway, 4956|
|Stavanger, Norway, 4011|
|Skane University Hospital|
|Lund, Sweden, SE-221 85|
|Karolinska University Hospital|
|Stockholm, Sweden, SE-171 76|
|Principal Investigator:||Dan Atar, Pr||Oslo University Hospital Ulleval|