TY - JOUR
T1 - Rationale and design of the Virginia Commonwealth University-Anakinra Remodeling Trial-3 (VCU-ART3)
T2 - A randomized, placebo-controlled, double-blinded, multicenter study
AU - Van Tassell, Benjamin W
AU - Lipinski, Michael J
AU - Appleton, Darryn
AU - Roberts, Charlotte S
AU - Kontos, Michael C
AU - Abouzaki, Nayef
AU - Melchior, Ryan
AU - Mueller, George
AU - Garnett, James
AU - Canada, Justin
AU - Carbone, Salvatore
AU - Buckley, Leo F
AU - Wohlford, George
AU - Kadariya, Dinesh
AU - Trankle, Cory R
AU - Oddi Erdle, Claudia
AU - Sculthorpe, Robin
AU - Puckett, Laura
AU - DeWilde, Christine
AU - Shah, Keyur
AU - Angiolillo, Dominick J
AU - Vetrovec, George
AU - Biondi-Zoccai, Giuseppe
AU - Arena, Ross
AU - Abbate, Antonio
N1 - © 2018 Wiley Periodicals, Inc.
PY - 2018/8
Y1 - 2018/8
N2 - There is clear association between the intensity of the acute inflammatory response during acute myocardial infarction (AMI) and adverse prognosis after AMI. Interleukin-1 (IL-1) is a pro-inflammatory cytokine released during AMI and involved in adverse remodeling and heart failure (HF). We describe a study to evaluate the safety and efficacy of IL-1 blockade using an IL-1 receptor antagonist (anakinra) during the acute phase of ST-segment elevation myocardial infarction (STEMI). The Virginia Commonwealth University-Anakinra Remodeling Trial-3 (VCU-ART3; http://www.ClinicalTrials.gov NCT01950299) is a phase 2, multicenter, double-blinded, randomized, placebo-controlled clinical trial comparing anakinra 100 mg once or twice daily vs matching placebo (1:1:1) for 14 days in 99 patients with STEMI. Patients who present to the hospital with STEMI within 12 hours of symptom onset will be eligible for enrollment. Patients will be excluded for a history of HF (functional class III-IV), severe valvular disease, severe kidney disease (stage 4-5), active infection, recent use of immunosuppressive drugs, active malignancy, or chronic autoimmune/auto-inflammatory diseases. We will measure the difference in the area under the curve for C-reactive protein between admission and day 14, separately comparing each of the anakinra groups with the placebo group. The P value will be considered significant if <0.025 to adjust for multiple comparisons. Patients will also be followed for up to 12 months from enrollment to evaluate cardiac remodeling (echocardiography), cardiac function (echocardiography), and major adverse cardiovascular outcomes (cardiovascular death, MI, revascularization, and new onset of HF).
AB - There is clear association between the intensity of the acute inflammatory response during acute myocardial infarction (AMI) and adverse prognosis after AMI. Interleukin-1 (IL-1) is a pro-inflammatory cytokine released during AMI and involved in adverse remodeling and heart failure (HF). We describe a study to evaluate the safety and efficacy of IL-1 blockade using an IL-1 receptor antagonist (anakinra) during the acute phase of ST-segment elevation myocardial infarction (STEMI). The Virginia Commonwealth University-Anakinra Remodeling Trial-3 (VCU-ART3; http://www.ClinicalTrials.gov NCT01950299) is a phase 2, multicenter, double-blinded, randomized, placebo-controlled clinical trial comparing anakinra 100 mg once or twice daily vs matching placebo (1:1:1) for 14 days in 99 patients with STEMI. Patients who present to the hospital with STEMI within 12 hours of symptom onset will be eligible for enrollment. Patients will be excluded for a history of HF (functional class III-IV), severe valvular disease, severe kidney disease (stage 4-5), active infection, recent use of immunosuppressive drugs, active malignancy, or chronic autoimmune/auto-inflammatory diseases. We will measure the difference in the area under the curve for C-reactive protein between admission and day 14, separately comparing each of the anakinra groups with the placebo group. The P value will be considered significant if <0.025 to adjust for multiple comparisons. Patients will also be followed for up to 12 months from enrollment to evaluate cardiac remodeling (echocardiography), cardiac function (echocardiography), and major adverse cardiovascular outcomes (cardiovascular death, MI, revascularization, and new onset of HF).
KW - Antirheumatic Agents/administration & dosage
KW - C-Reactive Protein/metabolism
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Echocardiography
KW - Electrocardiography
KW - Female
KW - Follow-Up Studies
KW - Heart Failure/diagnosis
KW - Humans
KW - Interleukin 1 Receptor Antagonist Protein/administration & dosage
KW - Interleukin-1/blood
KW - Male
KW - Middle Aged
KW - Morbidity/trends
KW - ST Elevation Myocardial Infarction/blood
KW - Survival Rate/trends
KW - Treatment Outcome
KW - United States/epidemiology
KW - Ventricular Remodeling/drug effects
U2 - 10.1002/clc.22988
DO - 10.1002/clc.22988
M3 - Article
C2 - 30033595
VL - 41
SP - 1004
EP - 1008
JO - Clinical Cardiology
JF - Clinical Cardiology
SN - 0160-9289
IS - 8
ER -