Treatment With Aspirin Alone Versus Aspirin in Combination With Fondaparinux Before Early Coronary Assessment in Patients With Non-ST-Elevation Myocardial Infarction

NCT06710184 | Recruiting Phase 4

• 2 other identifiers: DAN-FOXY2024-517229-18-00
• Study Type: interventional
• Target: 5,076
• Locations: 1 country
• Sites: 10

Brief Summary

The main goal of this study is to compare two treatments in patients with a specific type of heart attack called Non-ST-elevation Myocardial Infarction (NSTEMI). The investigators want to find out whether using aspirin alone is as effective and safer than using aspirin together with a second blood thinner called fondaparinux. Both treatments will be given before a scheduled heart procedure called coronary angiography (CAG), which may include balloon dilation and stent placement (PCI) if needed. The current guidelines recommend using aspirin in combination with a second blood thinner like fondaparinux before CAG and possible PCI. However, these recommendations are based on studies from the 1990s, a time when invasive procedures were not standard practice for these patients. In contrast, nearly all patients with NSTEMI in Denmark (96%) now undergo CAG within 72 hours. This change in practice raises questions about whether the older studies still provide a valid foundation for today's guidelines. The study aims to answer two questions:

1. 1.Is aspirin alone as effective as aspirin combined with fondaparinux before early CAG and possible PCI?
2. 2.Is aspirin alone safer, with a lower risk of severe bleeding, compared to the combination treatment?

Conditions

Acute Myocardial Infarction (AMI); NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI)

Keywords

Acute Myocardial Infarction; Non-ST Segment Elevation Myocardial Infarction; Aspirin; Fondaparinux; Anticoagulation; Coronary Angiography; Percutaneus Coronary Intervention; Acute Coronay Syndrome; Early Invasive Treatment; Refractory ischemia; Bleeding risk; Mortality; Randomized Controlled Trial; New Myocardial Infarction; Non-inferiority Trial; Multicenter Study; Antithrombotic

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of mortality, new myocardial infarction, and clinical deterioration resulting in acute CAG

  Composite of 30-day mortality, 30-day new MI, and clinical deterioration resulting in acute CAG. The endpoints will be assessed through review of the patient's medical journal. New Myocardial infarction (MI): Defined as a new MI after the early invasive strategy. Clinical deterioration resulting in acute CAG: Defined as conversion to acute coronary angiography (CAG) before the scheduled. Indication for acute CAG is based on the ESC guidelines of "very high risk" NSTEMI (1):

  The primary endpoints will be assessed after day 30.

Secondary Outcomes (5)

• All-cause mortality

  Up to 10 years

• New Myocardial Infarction

  Up to 10 years

• Cerebrovascular accident (CVA)

  Up to 30 days

• Length of hospital stay

  Up to 30 days

• Left Ventricular Ejection Fraction at Discharge

  Up to 30 days

Other Outcomes (2)

• Severe bleeding

  Up to 30 days

• Severe thrombotic event

  Up to 30 days

Study Arms (2)

Aspirin alone

EXPERIMENTAL

Treatment with aspirin alone. The intervention is removal of treatment with fondaparinux

Drug: Aspirin

Standard Treatment - Aspirin and Fondaparinux

ACTIVE COMPARATOR

Standard treatment regime with Aspirin in combination with Fondaparinux.

Drug: Aspirin; Drug: Fondaparinux Sodium

Interventions

Aspirin DRUG

Aspirin bolus of 300 mg followed by 75 mg daily until CAG

Aspirin alone; Standard Treatment - Aspirin and Fondaparinux

Fondaparinux Sodium DRUG

Fondaprinux 2.5 mg subcutaneus daily until CAG (1.5 mg for patients with eGFR 20-50 ml/min/1.73m2)

Standard Treatment - Aspirin and Fondaparinux

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of NSTEMI verified by:
• Rise or/and fall in cardiac troponin (cTN) and
• Symptoms of acute ischemia or ECG-changes compatible with acute ischemia.
• Age above 18 years old
• Expected remaining lifespan above 1 year
• Informed consent

You may not qualify if:

• Treatment with any anticoagulants before enrollment and randomization
• Including any direct anticoagulant (DOAC), LMWH, UFH or warfarin.
• Not possible with CAG and PCI within 72 hours
• Unsuitable for CAG and possible PCI due to poor condition
• Estimated glomerular filtration rate (eGFR) \< 20 ml/min/1.73m2
• Known liver disease
• Active bleeding or high risk of bleeding where treatment with Fondaparinux is contraindicated.
• Anemia (B-Hemoglobin \< 6.0 mmol/l)
• Pregnancy or breastfeeding
• Endocarditis
• Indication for acute CAG before enrollment and randomization:
• ST-elevation Myocardial Infarction (STEMI)
• Patients classified as "Very High Risk" according to ESC guidelines, defined as(1):
• Hemodynamic instability (in need of inotropic support) or cardiogenic shock (DANGER-SHOCK criteria (20)) at time of admission.
• Acute heart failure because of presumed acute ischemia

Sponsors & Collaborators

• Danske Regioner: collaborator
• Aalborg University Hospital: collaborator
• Odense University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Randers Regional Hospital: collaborator
• Viborg Regional Hospital: collaborator
• Sydvestjysk Hospital Esbjerg: collaborator
• Lillebaelt Hospital, Kolding and Vejle, Denmark: collaborator
• Hospital of Southern Jutland: collaborator
• Horsens Hospital: collaborator
• Gødstrup Hospital: collaborator
• University of Aarhus: lead

Study Sites (10)

Regionshospitalet Gødstrup

Herning, Region Midt, 7400, Denmark

RECRUITING

Regionshospitalet Horsens

Horsens, Region Midt, 8700, Denmark

NOT YET RECRUITING

Regionshospitalet Viborg

Viborg, Region Midt, Denmark

RECRUITING

Aalborg Universitetshospital

Aalborg, Region Nord, 9000, Denmark

NOT YET RECRUITING

Sygehus Søndejylland, Aabenraa

Aabenraa, Region Syd, 6200, Denmark

RECRUITING

Esbjerg Sygehus

Esbjerg, Region Syd, 6700, Denmark

NOT YET RECRUITING

Sygehus Lillebælt, Kolding

Kolding, Region Syd, 6000, Denmark

RECRUITING

Odense Universitetshospital

Odense, Region Syd, 5000, Denmark

RECRUITING

Sygehus Lillebælt, Vejle

Vejle, Region Syd, 7100, Denmark

RECRUITING

Aarhus University Hospital, Department of Cardiology

Aarhus N, 8200, Denmark

RECRUITING

Related Publications (19)

• Kvalitetsudviklingsprogram RK. Dansk Hjerteregister - Årsrapport 2022. 2022.

  BACKGROUND

• Ashkan E, Pedersen CK, Høfsten DE, et al. Behandlingsvejledning I Akut Koronart Syndrom Dansk Cardiologisk Selskab.

  BACKGROUND

• Moller JE, Engstrom T, Jensen LO, Eiskjaer H, Mangner N, Polzin A, Schulze PC, Skurk C, Nordbeck P, Clemmensen P, Panoulas V, Zimmer S, Schafer A, Werner N, Frydland M, Holmvang L, Kjaergaard J, Sorensen R, Lonborg J, Lindholm MG, Udesen NLJ, Junker A, Schmidt H, Terkelsen CJ, Christensen S, Christiansen EH, Linke A, Woitek FJ, Westenfeld R, Mobius-Winkler S, Wachtell K, Ravn HB, Lassen JF, Boesgaard S, Gerke O, Hassager C; DanGer Shock Investigators. Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock. N Engl J Med. 2024 Apr 18;390(15):1382-1393. doi: 10.1056/NEJMoa2312572. Epub 2024 Apr 7.

  PMID: 38587239 BACKGROUND

• Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.

  PMID: 21670242 BACKGROUND

• Cohen M, Adams PC, Parry G, Xiong J, Chamberlain D, Wieczorek I, Fox KA, Chesebro JH, Strain J, Keller C, et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation. 1994 Jan;89(1):81-8. doi: 10.1161/01.cir.89.1.81.

  PMID: 8281698 BACKGROUND

• Gurfinkel EP, Manos EJ, Mejail RI, Cerda MA, Duronto EA, Garcia CN, Daroca AM, Mautner B. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. J Am Coll Cardiol. 1995 Aug;26(2):313-8. doi: 10.1016/0735-1097(95)80001-w.

  PMID: 7608429 BACKGROUND

• Theroux P, Ouimet H, McCans J, Latour JG, Joly P, Levy G, Pelletier E, Juneau M, Stasiak J, deGuise P, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988 Oct 27;319(17):1105-11. doi: 10.1056/NEJM198810273191701.

  PMID: 3050522 BACKGROUND

• Cohen M, Adams PC, Hawkins L, Bach M, Fuster V. Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). Am J Cardiol. 1990 Dec 1;66(19):1287-92. doi: 10.1016/0002-9149(90)91155-y.

  PMID: 2244556 BACKGROUND

• Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators; Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006 Apr 6;354(14):1464-76. doi: 10.1056/NEJMoa055443. Epub 2006 Mar 14.

  PMID: 16537663 BACKGROUND

• Eikelboom JW, Anand SS, Malmberg K, Weitz JI, Ginsberg JS, Yusuf S. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet. 2000 Jun 3;355(9219):1936-42. doi: 10.1016/S0140-6736(00)02324-2.

  PMID: 10859038 BACKGROUND

• Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. JAMA. 1996 Sep 11;276(10):811-5.

  PMID: 8769591 BACKGROUND

• Cook BW. Anticoagulation management. Semin Intervent Radiol. 2010 Dec;27(4):360-7. doi: 10.1055/s-0030-1267849.

  PMID: 22550377 BACKGROUND

• Schiele F. Fondaparinux and acute coronary syndromes: update on the OASIS 5-6 studies. Vasc Health Risk Manag. 2010 Apr 15;6:179-87. doi: 10.2147/vhrm.s6099.

  PMID: 20407625 BACKGROUND

• Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth. 2014 Sep;58(5):515-23. doi: 10.4103/0019-5049.144643.

  PMID: 25535411 BACKGROUND

• Zaman AG, Helft G, Worthley SG, Badimon JJ. The role of plaque rupture and thrombosis in coronary artery disease. Atherosclerosis. 2000 Apr;149(2):251-66. doi: 10.1016/s0021-9150(99)00479-7.

  PMID: 10729375 BACKGROUND

• Bhatt DL, Hulot JS, Moliterno DJ, Harrington RA. Antiplatelet and anticoagulation therapy for acute coronary syndromes. Circ Res. 2014 Jun 6;114(12):1929-43. doi: 10.1161/CIRCRESAHA.114.302737.

  PMID: 24902976 BACKGROUND

• Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Dec 23;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017. Epub 2014 Sep 23. No abstract available.

  PMID: 25260718 BACKGROUND

• Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Juni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. No abstract available.

  PMID: 37622654 BACKGROUND

• Fur CB, Olsen NT, Lassen JF, Eftekhari A, Stengaard C, Pedersen CK, Rasmussen MB, Terkelsen CJ. Design and rationale of aspirin versus aspirin and fondaparinux prior to early invasive strategy in patients with NSTEMI: The FOXY trial. Am Heart J. 2026 Feb;292:107274. doi: 10.1016/j.ahj.2025.09.006. Epub 2025 Sep 11.

  PMID: 40945808 DERIVED

MeSH Terms

Conditions

Ischemia

Interventions

Aspirin; Fondaparinux

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Oligosaccharides; Polysaccharides; Carbohydrates

Central Study Contacts

Christian B Fur, MD

CONTACT

+4524918071; chbyni@rm.dk

Christian J Terkelsen, MD, PhD, DmSC

CONTACT

christian.terkelsen@skejby.rm.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, open-label, non-inferiority, randomized controlled trial

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: November 29, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 4, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (10)