Interleukin-1 (IL-1) Blockade in Acute Myocardial Infarction (VCU-ART3) (VCU-ART3)

Interleukin-1 Blockade With Anakinra in Patients With ST-segment Elevation Myocardial Infarction - the Virginia Commonwealth University Anakinra Remodeling Trial 3

VCU-ART3 is a double-blind randomized clinical trial of anakinra high dose vs anakinra standard dose vs placebo in patients with ST-segment elevation myocardial infarction (STEMI) measuring the effects on the acute rise and fall of the plasma C reactive protein levels during the first 14 days.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: Anakinra 100 mg; Drug: Anakinra 100 mg; Drug: Placebo

Detailed Description

VCU-ART3 is a double-blind randomized clinical trial of anakinra high dose vs anakinra standard dose vs placebo in patients with ST-segment elevation myocardial infarction (STEMI) measuring the effects on the acute rise and fall of the plasma C reactive protein levels during the first 14 days

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

In order to be eligible for this study, patients must meet ALL the 3 Inclusion criteria and NONE of the Exclusion criteria.

1. Acute STEMI defined as chest pain (or equivalent) with an onset within 12 hours and ECG evidence of ST segment elevation (>1 mm) in 2 or more anatomically contiguous leads that is new or presumably new
2. Planned or completed coronary angiogram for potential intervention
3. Age>21

EXCLUSION CRITERIA:

• Inability to give informed consent
• Pregnancy
• Preexisting congestive heart failure (American Heart Association/American College of Cardiology class C-D, New York Heart Association III-IV)
• Preexisting severe left ventricular dysfunction (EF<20%)
• Preexisting severe valvular heart disease
• Active infections (acute or chronic) - excluding Hepatitis C Virus (HCV)+ with undetectable RNA
• Recent (<14 days) or active use of anti-inflammatory drugs (not including non-steroidal anti-inflammatory drugs [NSAIDs] or corticosteroids used for IV dye allergy only)
• Chronic inflammatory disease (including but not limited to rheumatoid arthritis, systemic lupus erythematosus)
• Active malignancy - excluding carcinoma in situ [any organ] and non-melanoma skin cancer
• Anticipated need for cardiac surgery
• Neutropenia (absolute neutrophil count<1,800/mm3)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anakinra (standard dose); Anakinra 100 mg daily for 14 days	Drug: Anakinra 100 mg; Anakinra 100 mg starting immediately and then every 24 hours; Other Names: Kineret; Drug: Anakinra 100 mg; Anakinra 100 mg starting 12 hours after first dose and then every 24 hours (so that Anakinra is given every 12 hours); Other Names: Kineret; Drug: Placebo; Placebo 0.67 ml injections twice daily; Other Names: Placebo injections twice daily
Experimental: Anakinra (high dose); Anakinra 100 mg twice daily for 14 days	Drug: Anakinra 100 mg; Anakinra 100 mg starting immediately and then every 24 hours; Other Names: Kineret; Drug: Anakinra 100 mg; Anakinra 100 mg starting 12 hours after first dose and then every 24 hours (so that Anakinra is given every 12 hours); Other Names: Kineret
Placebo Comparator: Placebo; Placebo for 14 days	Drug: Placebo; Placebo 0.67 ml injections twice daily; Other Names: Placebo injections twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Phase Response (CRP Levels)	Comparison of area-under-the-curve for CRP up to day 14	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular End-systolic Volume	Placebo corrected interval change in left ventricular end-systolic volume over 12 months	12 months
Left Ventricular Ejection Fraction	Placebo-corrected interval changes in left ventricular ejection fraction over 12 months	12 months
Heart Failure	New onset of heart failure symptoms (NYHA II-IV)	12 months

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)

Publications and helpful links

General Publications

• Silvis MJM, Demkes EJ, Fiolet ATL, Dekker M, Bosch L, van Hout GPJ, Timmers L, de Kleijn DPV. Immunomodulation of the NLRP3 Inflammasome in Atherosclerosis, Coronary Artery Disease, and Acute Myocardial Infarction. J Cardiovasc Transl Res. 2021 Feb;14(1):23-34. doi: 10.1007/s12265-020-10049-w. Epub 2020 Jul 9.
• Abbate A, Trankle CR, Buckley LF, Lipinski MJ, Appleton D, Kadariya D, Canada JM, Carbone S, Roberts CS, Abouzaki N, Melchior R, Christopher S, Turlington J, Mueller G, Garnett J, Thomas C, Markley R, Wohlford GF, Puckett L, Medina de Chazal H, Chiabrando JG, Bressi E, Del Buono MG, Schatz A, Vo C, Dixon DL, Biondi-Zoccai GG, Kontos MC, Van Tassell BW. Interleukin-1 Blockade Inhibits the Acute Inflammatory Response in Patients With ST-Segment-Elevation Myocardial Infarction. J Am Heart Assoc. 2020 Mar 3;9(5):e014941. doi: 10.1161/JAHA.119.014941. Epub 2020 Mar 3.
• Van Tassell BW, Lipinski MJ, Appleton D, Roberts CS, Kontos MC, Abouzaki N, Melchior R, Mueller G, Garnett J, Canada J, Carbone S, Buckley LF, Wohlford G, Kadariya D, Trankle CR, Oddi Erdle C, Sculthorpe R, Puckett L, DeWilde C, Shah K, Angiolillo DJ, Vetrovec G, Biondi-Zoccai G, Arena R, Abbate A. Rationale and design of the Virginia Commonwealth University-Anakinra Remodeling Trial-3 (VCU-ART3): A randomized, placebo-controlled, double-blinded, multicenter study. Clin Cardiol. 2018 Aug;41(8):1004-1008. doi: 10.1002/clc.22988. Epub 2018 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): December 23, 2018
• Study Completion (Actual): December 23, 2018

Study Registration Dates

• First Submitted: September 4, 2013
• First Submitted That Met QC Criteria: September 20, 2013
• First Posted (Estimate): September 25, 2013

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 3, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: HM20000024; 1R34HL121402-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No