Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
287
Countries
2
Sites
20
Left ventricular thrombosis.
The primary objective of this study is to compare the effect of apixaban versus warfarin with respect to thrombus resolution in patients with left ventricular thrombus after acute myocardial infarction (AMI).
Key facts
- Sponsor
- Karolinska Institutet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 9 Apr 2025 → ongoing
- Decision date (initial)
- 2026-03-31
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Hjärt-Lungfonden · ALF medel (SLL) · Vetenskapsrådet (VR)
External identifiers
- EU CT number
- 2024-514416-28-00
- ClinicalTrials.gov
- NCT06515730
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The primary objective of this study is to compare the effect of apixaban versus warfarin with respect to thrombus resolution in patients with left ventricular thrombus after acute myocardial infarction (AMI).
Secondary objectives 7
- To compare apixaban versus warfarin with respect to clinically relevant bleeding.
- To compare apixaban versus warfarin with respect to major bleeding.
- To compare apixaban versus warfarin with respect to separate bleeding outcomes.
- To compare apixaban versus warfarin with respect to major adverse cardiovascular events.
- To compare apixaban versus warfarin with respect to net clinical benefit defined as MACE (Major Adverse Cardiovascular Events) and clinically relevant bleeding.
- To compare apixaban versus warfarin with respect to ischemic stroke and systemic embolism.
- To evaluate the rate of thrombus recurrence one year after the index event.
Conditions and MedDRA coding
Left ventricular thrombosis.
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10000891 | Acute myocardial infarction | 100000004849 |
| 20.1 | LLT | 10080067 | Left ventricular thrombosis | 10007541 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Participants must be ≥ 18 years at the time of signing the informed consent.
- Left ventricular thrombus confirmed on transthoracic echocardiogram (TTE) or when inconclusive documented on cardiac magnet resonance imaging (MRI) or computed tomography (CT) on day 1-28 after the acute myocardial infarction.
- The subject has given their written consent to participate in the trial which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and study protocol.
- Criteria applicable only for female subjects: A) Women of childbearing potential must provide a negative pregnancy test at inclusion, not be breastfeeding and be willing and able to use highly effective contraception during the treatment and up to 3 months after the last dose of study drug; B) Women of non-childbearing potential must be 1 year post-menopausal.
Exclusion criteria 8
- Ongoing treatment with anticoagulant therapy due to: A) Mechanical heart valve prosthesis (not including transcatheter aortic valve replacement); B) Atrial fibrillation with or without significant mitral valve stenosis; C) Venous thromboembolism requiring anticoagulant therapy; D) Thrombophilia requiring anticoagulant therapy; E) Preexisting left ventricular thrombus already on anticoagulant therapy; F) Other reasons for anticoagulant therapy.
- High bleeding risk: A) Active non-trivial bleeding; B) Known chronic bleeding disorder; C) Severe anemia defined as hemoglobin < 80g/L; D) Thrombocytopenia defined as thrombocytes <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 (active substance or excipients).
- 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 that may interfere with participants safety and or compliance as judged at the discretion of the investigator.
- Any other condition, as judged by the investigator, that would make the participant unsafe or unsuitable for the study (anticipated non-compliance or vulnerability) or very short life expectancy < 6 months.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Thrombus resolution will be evaluated by TTE (Transthoracic echocardiogram), preferably contrast-enhanced, at 3 months. Should TTE be inconclusive, cardiac magnet resonance imaging (MRI) or cardiac computed tomography (CCT) is recommended to evaluate the primary endpoint.
Secondary endpoints 7
- Clinically relevant bleeding - BARC (Bleeding Academy Research Consortium) 2, 3 or 5 bleeding.
- Major bleeding BARC 3 or 5 bleeding.
- Individual bleeding endpoints (Fatal bleeding, intracranial hemorrhage, GI bleeding, urogenital bleeding and bleeding of other sources).
- Major adverse cardiovascular events (MACE). Composite of non-fatal myocardial infarction, non-fatal ischemic stroke and cardiovascular death.
- Net clinical benefit: Composite of MACE and BARC 2, 3 or 5 bleeding.
- Ischemic stroke and systemic embolism.
- Recurrence of LV thrombus at 12 months.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Eliquis 5 mg film-coated tablets
PRD1722225 · Product
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF02 — -
- Marketing authorisation
- EU/1/11/691/014
- MA holder
- BRISTOL-MYERS SQUIBB/PFIZER EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Eliquis 2.5 mg film-coated tablets
PRD1722226 · Product
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF02 — -
- Marketing authorisation
- EU/1/11/691/015
- MA holder
- BRISTOL-MYERS SQUIBB/PFIZER EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
PRD9483319 · Product
- Active substance
- Warfarin Sodium
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 2.5 mg milligram(s)
- Max total dose
- 2.5 mg milligram(s)
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AA03 — WARFARIN
- Marketing authorisation
- 6897
- MA holder
- ORIFARM HEALTHCARE A/S
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 2
OPTISON 0.19 mg/ml dispersion for injection
PRD10888759 · Product
- Active substance
- Perflutren
- Pharmaceutical form
- DISPERSION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 3.0 ml millilitre(s)
- Max total dose
- 8.7 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V08DA01 — MICROSPHERES OF HUMAN ALBUMIN
- Marketing authorisation
- EU/1/98/065/001
- MA holder
- GE HEALTHCARE AS
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SonoVue 8 microlitres/mL powder and solvent for dispersion for injection
PRD451459 · Product
- Active substance
- Sulfur Hexafluoride
- Pharmaceutical form
- DISPERSION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 8.0 µl microlitre(s)
- Max total dose
- 2.0 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V08DA05 — SULFUR HEXAFLUORIDE
- Marketing authorisation
- EU/1/01/177/002
- MA holder
- BRACCO INTERNATIONAL BV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Karolinska Institutet
- Sponsor organisation
- Karolinska Institutet
- Address
- Nobels Vag 6
- City
- Solna
- Postcode
- 171 65
- Country
- Sweden
Scientific contact point
- Organisation
- Karolinska Institutet
- Contact name
- FOU
Public contact point
- Organisation
- Karolinska Institutet
- Contact name
- FOU
Locations
2 EU/EEA countries · 20 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Authorised, recruitment pending | 75 | 2 |
| Sweden | Ongoing, recruiting | 212 | 18 |
| Rest of world | — | 0 | — |
Investigational sites
Rigshospitalet
Department of Cardiology, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Oe
Aarhus Universitetshospital
Department of Cardiology, Palle Juul-Jensens Boulevard 99, 8200, Århus
Region Gotland
Department of Medicine, Visby, S:t Goransgatan 5, Visby Domkyrkofors., Visby
Region Blekinge
Department of Cardiology, Thoracic centre, Lasarettsvagen, 371 85, Karlskrona
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Kardiologi, Bla Straket 5, Goteborgs Annedal, Goteborg
Falu Lasarett
Kardiologikliniken, Lasarettvagen 10, Kardiologiska kliniken/Hjartmottagningen, Falun
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Medicin och akutsjukvård, Goteborgsvagen 31, Fassberg, Molndal
Region Oerebro Laen
Kardiologi, Sodra Grev Rosengatan, 701 85, Orebro
Region Oestergoetland
Kardiologikliniken, Universitetssjukhuset I Linkoping, 581 85, Linkoping
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Medicin, Geriatrik och Akutmedicin, Diagnosvagen 11, Harlanda, Gothenburg
Danderyds Sjukhus AB
Kardiologi, Morbygardsvagen 88, 182 88, Danderyd
Karolinska University Hospital
ME kardiologi, Eugeniavagen 3, 171 64, Solna
Region Skane Skanes Universitetssjukhus
Kardiologi, Entregatan 7, 222 42, Lund
Capio S:t Goerans Sjukhus AB
Hjärtkliniken, Sankt Goransplan 1, Vastermalm, Stockholm
Karolinska University Hospital
Medicine, Halsovagen, Flemingsberg, Huddinge
Västerås Regional Hospital
Medicinkliniken, Regionhuset 721 89 Västerås, Sweden, västerås
Region Skane Skanes Universitetssjukhus
Kardiologi, Ruth Lundskogs Gata 3, Malmo St Johannes, Malmo
Södersjukhuset Sachsska Barnsjukhuset
Kardiologikliniken, Sjukhusbacken 10, 118 83, Stockholm
Uppsala University Hospital
ME kardiologi, Akademiska Sjukhuset, 751 85, Uppsala
Vrinnevisjukhuset I Norrkoeping Region Oestergoetland
Kardiologkliniken, S Borg, Gamla Ovagen 25, Norrkoping
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Sweden | 2025-04-09 | 2025-04-09 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 14 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | 3.0 RESOLVE-AMI studieprotokoll | 1 |
| Protocol (for publication) | RESOLVE-AMI studieprotokoll | 1 |
| Protocol (for publication) | RESOLVE-AMI studieprotokoll TC | 1 |
| Protocol (for publication) | Summary of Changes SM-1_Changes EU trial number | 1 |
| Recruitment arrangements (for publication) | Recruitment arrangements | 2 |
| Recruitment arrangements (for publication) | Resolve-AMI Forfarande-for-rekrytering-och-samtyckesprocess | 1 |
| Subject information and informed consent form (for publication) | Aarhus Informed Consent 2 | 2 |
| Subject information and informed consent form (for publication) | Informed Consent DK | 2 |
| Subject information and informed consent form (for publication) | Informed Consent form | 1 |
| Subject information and informed consent form (for publication) | Informed Consent TC | 1 |
| Subject information and informed consent form (for publication) | Summary of Changes IC SM-1 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Produktresume Eliquis 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Waran tablet SmPC | 1 |
| Synopsis of the protocol (for publication) | RESOLVE-AMI Synopsis | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-08-13 | Sweden | Acceptable 2024-11-04
|
2024-11-04 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-01-10 | Sweden | Acceptable | 2025-03-10 |
| 3 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-09-08 | Sweden | Acceptable | 2025-09-24 |
| 4 | SUBSEQUENT ADDITION OF MSC | APP-4 | 2025-12-22 | 2026-03-31 |