BACKGROUND: Previous studies suggested that RheothRx (poloxamer 188) reduces infarct size and improves left ventricular (LV) function in acute myocardial infarction (AMI). We therefore evaluated the effects of various doses of RheothRx in 2948 patients presenting with AMI. METHODS AND RESULTS: Patients were randomized to a control group (n = 963) or to receive RheothRx. Patients receiving RheothRx were allocated to receive a 1-hour bolus only (regimen A, n = 844), an additional 11-hour infusion at a low dose (target serum concentration of 0.5 mg/mL) (regimen Y, n = 490), or an additional 23-hour infusion at a low dose (regimen B, n = 483). Three higher doses (1-hour bolus+low-dose infusion for 47 hours, 1-hour bolus+high dose, target serum concentration of 1.0 mg/ml for 24 hours, or 1-hour bolus+high dose for 48 hours) were discontinued because of high rates of renal dysfunction (8.8%). Renal dysfunction was also observed at lower doses (regimen A, 3.1%; Y, 2.7%; and B, 4.1%) compared with the control patients (1.0%). There was no significant difference in the composite outcome of death, cardiogenic shock, or reinfarction at 35 days (all RheothRx, 13.6%; control, 12.7%). There was a higher incidence of sinus tachycardia (24.7% versus 21.6%, P = .02), atrial flutter (3.0% versus 1.3%, P = .019), atrial fibrillation (10.2% versus 7.3%, P = .082), pericarditis (6.6% versus 4.7%, P = .055), and clinical (21.9% versus 17.9%, P = .005) and radiological (15.3% versus 12.3%, P = .12) evidence of heart failure. This was associated with a lower LV ejection fraction (n = 1053) in treated patients (by = -0.02, P = .026), but there was little difference (P = .34) in infarct size (n = 1088). CONCLUSIONS: In this study of nearly 3000 patients, RheothRx had no effect on mortality, reinfarction, or cardiogenic shock and an adverse effect on renal function, LV ejection fraction, and various clinical manifestations of LV dysfunction or heart failure.
RCT Entities:
BACKGROUND: Previous studies suggested that RheothRx (poloxamer 188) reduces infarct size and improves left ventricular (LV) function in acute myocardial infarction (AMI). We therefore evaluated the effects of various doses of RheothRx in 2948 patients presenting with AMI. METHODS AND RESULTS:Patients were randomized to a control group (n = 963) or to receive RheothRx. Patients receiving RheothRx were allocated to receive a 1-hour bolus only (regimen A, n = 844), an additional 11-hour infusion at a low dose (target serum concentration of 0.5 mg/mL) (regimen Y, n = 490), or an additional 23-hour infusion at a low dose (regimen B, n = 483). Three higher doses (1-hour bolus+low-dose infusion for 47 hours, 1-hour bolus+high dose, target serum concentration of 1.0 mg/ml for 24 hours, or 1-hour bolus+high dose for 48 hours) were discontinued because of high rates of renal dysfunction (8.8%). Renal dysfunction was also observed at lower doses (regimen A, 3.1%; Y, 2.7%; and B, 4.1%) compared with the control patients (1.0%). There was no significant difference in the composite outcome of death, cardiogenic shock, or reinfarction at 35 days (all RheothRx, 13.6%; control, 12.7%). There was a higher incidence of sinus tachycardia (24.7% versus 21.6%, P = .02), atrial flutter (3.0% versus 1.3%, P = .019), atrial fibrillation (10.2% versus 7.3%, P = .082), pericarditis (6.6% versus 4.7%, P = .055), and clinical (21.9% versus 17.9%, P = .005) and radiological (15.3% versus 12.3%, P = .12) evidence of heart failure. This was associated with a lower LV ejection fraction (n = 1053) in treated patients (by = -0.02, P = .026), but there was little difference (P = .34) in infarct size (n = 1088). CONCLUSIONS: In this study of nearly 3000 patients, RheothRx had no effect on mortality, reinfarction, or cardiogenic shock and an adverse effect on renal function, LV ejection fraction, and various clinical manifestations of LV dysfunction or heart failure.
Authors: Dewayne Townsend; Immanuel Turner; Soichiro Yasuda; Joshua Martindale; Jennifer Davis; Michael Shillingford; Joe N Kornegay; Joseph M Metzger Journal: J Clin Invest Date: 2010-03-15 Impact factor: 14.808
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