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Hu23F2G Anti-Adhesion to Limit Cytotoxic Injury Following AMI - HALT-MI
Description:
HALT-MI was a multicenter, randomized double-blinded trial to evaluate the safety and efficacy of Hu23F2G (an antibody directed against the leukocyte CD11/CD18 integrin receptor) in reducing infarct size in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary angioplasty.
Hypothesis:
Compared to placebo, treatment with Hu23F2G would be associated with reduced infarct size as determined by single-photon emission computed tomography (SPECT) imaging in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).
Study Design
Study Design:
Patients Screened: 637
Patients Enrolled: 420
Mean Follow Up: 30 days
Mean Patient Age: 18-85; mean of 60
Female: 28
Patient Populations:
Age 18-85, chest pain or other typical signs or symptoms of acute MI of less than six hours, and a candidate for primary angioplasty with TIMI 0 or 1 flow on angiography. For anterior MI, ST-segment elevation of at least 2 mm in at least two contiguous precordial leads or new left bundle branch block. For inferior MI, at least 1 mm ST-segment elevation in two or more inferior limb leads with reciprocal ST depression of at least 0.5 mm in two or more precordial leads.
Exclusions:
History and ECG evidence of previous Q-wave MI or an ECG pattern that made the diagnosis of MI difficult, cardiogenic shock, treatment with thrombolytic therapy before study drug administration, a baseline serum creatinine of >2 mg/dl, evidence of an ongoing bacterial infection, pregnancy, or presence of other serious medical conditions
Primary Endpoints:
Infarct size, as assessed by technetium-99m sestamibi SPECT imaging at 5-9 days
Secondary Endpoints:
Clinical and adverse events at 30 days
Drug/Procedures Used:
Three arms: Hu23F2G 0.3 mg/kg intravenously (IV), Hu23F2G 1 mg/kg IV, or placebo, administered after diagnostic angiography
Concomitant Medications:
Aspirin and heparin (target ACT 250-300). Glycoprotein (GP) IIb/IIIa inhibitors were used at the discretion of the treating physician.
Principal Findings:
A total of 420 patients were enrolled. The study groups were well-balanced, with stents placed in 85% of patients, and GP IIb/IIIa inhibitors used in >65% of patients.
There were no significant differences in infarct size between the study groups (16% for placebo, 17.2% for 0.3 mg/kg dose, 16.6% for 1 mg/kg dose, p=0.8). No differences were seen when the data were analyzed in subgroups of anterior infarct location or in time from onset of symptoms to treatment. The area under the curve for creatine kinase-MB and TIMI frame counts were not different between groups.
There were no differences between groups when a composite clinical endpoint including death and recurrent MI was used. Urinary tract infections occurred more frequently in the treatment groups (6.3% for 0.3 mg/kg, 9.4% for 1 mg/kg, and 2.6% for placebo).
Interpretation:
The HALT-MI trial demonstrated no significant benefit associated with the use of Hu23F2G, an agent designed to inhibit neutrophil adhesion and thereby reperfusion injury in primary PCI for STEMI. These results are consistent with the results of the LIMIT AMI trial, which examined another antibody directed against the CD18 receptor in patients with acute STEMI treated with thrombolysis, and found no benefit associated with this treatment. It is unclear whether the study drug was ineffective or whether inadequate dosing or timing of administration may have led to the negative results in HALT-MI.
References:
Faxon DP, Gibbons RJ, Chronos NA, Gurbel PA, Sheehan F, for the HALT-MI Investigators. The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study. J Am Coll Cardiol 2002;40:1199-204.
Keywords: Myocardial Infarction, Reperfusion Injury, Urinary Tract Infections, Creatine Kinase, Chest Pain, Tomography, Emission-Computed, Single-Photon, Bundle-Branch Block, Neutrophils, Angioplasty, Balloon, Coronary, Platelet Membrane Glycoprotein IIb, Stents
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