Treatment With Apixaban Versus Warfarin in Patients With Left Ventricular Thrombus After Acute Myocardial Infarction (RESOLVE-AMI)

RandomizEd compariSOn of Apixaban Versus Warfarin in Patients With Left VEntricular Thrombus After Acute Myocardial Infarction (RESOLVE-AMI)

The optimal anticoagulant for the treatment of left ventricular (LV) thrombus following acute myocardial infarction (AMI) is unclear. The aim of this multicenter randomized study is to evaluate the efficacy of apixaban versus warfarin with respect to thrombus resolution in patients with LV thrombus after AMI.

Study Overview

• Status: Recruiting
• Conditions: Acute Myocardial Infarction; Left Ventricular Thrombus
• Intervention / Treatment: Drug: Apixaban; Drug: Warfarin

• Study Type: Interventional
• Enrollment (Estimated): 212
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eva Olofsson; Phone Number: +46707780897; Email: moa.simonsson@ki.se
• Study Contact Backup: Name: Stina Smetana; Phone Number: +46725841182; Email: stina.smetana@ki.se

Study Locations

• Sweden
  • Falun, Sweden
    • Not yet recruiting
    • Falu Lasarett
    • Contact: Elin Falås, MD; Phone Number: +46 23 49 00 00; Email: elin.falas@gmail.com
  • Gothenburg, Sweden
    • Not yet recruiting
    • Sahlgrenska University Hospital
    • Contact: Annica Ravn-Fischer, MD, PhD; Phone Number: +46 31 342 10 00; Email: annica.ravn-fischer@vgregion.se
  • Gothenburg, Sweden
    • Not yet recruiting
    • Sahlgrenska University hospital, Mölndal
    • Contact: Georgios Mourtzinis, MD, PhD; Phone Number: +46 31 342 10 00; Email: georgios.mourtzinis@vgregion.se
  • Gothenburg, Sweden
    • Not yet recruiting
    • Sahlgrenska University hospital, Östra
    • Contact: Katarina Glise-Sandblad Glise Sandblad, MD, PhD; Phone Number: +46 31 342 10 00; Email: katarina.glise.sandblad@vgregion.se
  • Linköping, Sweden
    • Not yet recruiting
    • Linkoping University Hospital
    • Contact: Mats Pettersson, MD, PhD; Phone Number: +46 10 103 00 00; Email: Mats.Pettersson@regionostergotland.se
  • Lund, Sweden
    • Recruiting
    • Skånes Universitetssjukhus Lund
    • Contact: Josef Dankiewicz, MD, PhD; Phone Number: + 46 4617 10 00; Email: josef.dankiewicz@gmail.com
  • Malmö, Sweden
    • Not yet recruiting
    • Skånes University hospital, Malmö
    • Contact: Helena Grauen Larsen, MD, PhD; Phone Number: +46 40 33 10 00; Email: Helena.GrauenLarsen@skane.se
  • Nörrköping, Sweden
    • Not yet recruiting
    • Vrinnevi Hospital
    • Contact: Malgorzata Pierscinska-Jedra, MD; Phone Number: +46 10 103 00 00; Email: Malgorzata.Pierscinska-Jedra@regionostergotland.se
  • Stockholm, Sweden
    • Not yet recruiting
    • Sodersjukhuset
    • Contact: Robin Hofmann, MD, PhD; Phone Number: +46 8 123 610 00; Email: robin.hofmann@regionstockholm.se
  • Stockholm, Sweden, 17177
    • Recruiting
    • Karolinska Insitutet
    • Contact: Moa Simonsson, MD, PhD; Phone Number: +46707411272; Email: moa.simonsson@regionstockholm.se
  • Stockholm, Sweden
    • Not yet recruiting
    • Danderyds Hospital
    • Contact: Mika Skeppholm; Phone Number: + 46 8 123 550 00; Email: mika.skeppholm@regionstockholm.se
  • Stockholm, Sweden
    • Recruiting
    • Karolinska Univerity Hospital
    • Contact: Moa Simonsson, MD, PhD; Phone Number: +46 707411272; Email: moa.simonsson@ki.se
  • Stockholm, Sweden
    • Not yet recruiting
    • Sankt Gorans Hospital
    • Contact: Emil Grönlund, MD; Phone Number: +46 8 587 010 00; Email: emil.gronlund@capiostgoran.se
  • Uppsala, Sweden
    • Not yet recruiting
    • Uppsala Akademiska hospital
    • Contact: Christina Christersson; Phone Number: +46 18 611 00 00; Email: Christina.Christersson@medsci.uu.se
  • Västerås, Sweden
    • Not yet recruiting
    • Västmanlands hospital, Västerås
    • Contact: Anders Nordfors, MD, PhD; Phone Number: +46 21 17 30 00; Email: anders.nordfors@regionvastmanland.se
  • Örebro, Sweden
    • Not yet recruiting
    • Orebro University Hospital
    • Contact: Robin Gustafsson, MD, PhD; Phone Number: +46 19 602 10 00; Email: robin.gustafsson@regionorebrolan.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years at the time of signing the informed consent
• LV thrombus confirmed on TTE* day 1-28 after the AMI
• Signed informed consent
• Criteria applicable only for female subjects: Women of childbearing potential must provide a negative pregnancy test not be breastfeeding and be willing and able to use highly effective contraception. Women of non-childbearing potential must be 1 year post-menopausal.

Exclusion Criteria:

• Ongoing* treatment with anticoagulant therapy due to Mechanical heart valve prosthesis Atrial fibrillation with or without significant mitral valve stenosis Venous thromboembolism requiring anticoagulant therapy Thrombophilia requiring anticoagulant therapy Preexisting LV thrombus already treated with anticoagulant therapy Other reasons for anticoagulant therapy
• High bleeding risk Active non-trivial bleeding Known chronic bleeding disorder Severe anemia defined as hemoglobin < 80g/L Thrombocytopenia defined as platelet count < 80 x 10^9
• Known significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) or known hepatic insufficiency classified as Child-Pugh C or D at randomization
• Known allergy, intolerance or hypersensitivity to either of the study interventions
• Any contraindication for the use of an anticoagulant or listed in the local labelling for apixaban or warfarin.
• Participation in other study investigating effects and safety of anticoagulant treatment.
• Known current alcohol or drug abuse
• Any other condition, as judged by the investigator, that would make the participant unsafe or unsuitable for the study or life expectancy < 6 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apixaban; Apixaban 5 mg twice a day, reduced to 2.5 mg twice a day for participants with any 2 of following criteria: age > 80 years, serum creatinine > 133 μmol/L or body weight <60 kg. Participants with severe renal failure defined as creatinine clearance 15-29 ml/min/1.73 m2, should also receive the reduced dose of 2.5 mg twice a day.	Drug: Apixaban; 5 mg tablet twice a daily with dose reduction according to label; Other Names: Eliquis
Active Comparator: Warfarin; Warfarin 2,5 mg once daily with individual dosing according to coagulation assays with an international normalized ratio (INR) goal of 2.0-3.0. Bridging with low-molecular-weight-heparin with a dose of dalteparin 200 units/kg but maximum 18 000 units or enoxaparin 150 units/kg, until therapeutic INR is recommended.	Drug: Warfarin; 2.5 mg tablet once daily, with individual dosing according to coagulation tests; Other Names: Waran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and proportion of participants with thrombus resolution at 3 months	Thrombus resolution will be evaluated on transthoracic echocardiogram (TTE*) at 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Separate bleeding outcomes at 3 and 12 months	Separate bleeding outcomes defined as fatal, intracranial, gastro-intestinal uro-genital or other bleeding	3 and 12 months
Stroke or systemic embolism at 3 and 12 months	Composite of ischemic stroke or systemic embolism	3 and 12 months
LV thrombus status at 12 months	Recurrence (or in absence of resolution of LV thrombus at 3 months, persistence) of LV thrombus on TTE at 12 months	12 months
Clinically relevant bleeding at 3 and 12 months	Clinical relevant bleeding defined as Bleeding Academy Research Consortium (BARC) 2, 3 or 5 bleeding. The BARC bleeding scale ranges from 0 to 5, where 0 is equal to no bleeding, with increasing severity from 1 through 5, where 5 represents fatal bleeding. Major bleeding is most often defined as BARC 3 and 5. BARC 4 bleeding is coronary artery bypass grafting (CABG) related bleeding.	3 and 12 months
Severe bleeding at 3 and 12 months	Severe bleeding defined as BARC 3 or 5. For definition of the BARC bleeding scale please see Outcome 2 above.	3 and 12 months
Major adverse cardiovascular outcomes (MACE) at 3 and 12 months	MACE is defined as a composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death	3 and 12 months
Net adverse clinical outcomes	Composite of MACE and. BARC 2, 3 or 5 bleeding. For definition of MACE and BARC bleeding scale please see Outcome 2 and 5 above.	3 and 12 months

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: The Swedish Research Council; Swedish Heart Lung Foundation; Karolinska Trial Alliance; Stockholm County Council ALF/PPG
• Investigators: Principal Investigator: Moa Simonsson, MD, PhD, Department of Medicine Solna, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2025
• Primary Completion (Estimated): April 8, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: warfarin; Apixaban
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Embolism and Thrombosis; Myocardial Ischemia; Ischemia; Thrombosis; Myocardial Infarction; Infarction; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Apixaban; Warfarin
• Other Study ID Numbers: RESOLVE-AMI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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