NCT04436978

Brief Summary

The optimal antithrombotic management in patients with coronary artery disease (CAD) and concomitant atrial fibrillation (AF) is unknown. AF patients are treated with oral anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor, to prevent stent thrombosis (ST) and myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with triple antithrombotic therapy (TAT, i.e. OAC plus aspirin and P2Y12 inhibitor) to prevent ischemic complications. However, TAT doubles or even triples the risk of major bleeding complications. More recently, several clinical studies demonstrated that omitting aspirin, a strategy known as dual antithrombotic therapy (DAT) is safer compared to TAT with comparable efficacy. However, pooled evidence from recent meta-analyses suggests that patients treated with DAT are at increased risk of MI and ST. Insights from the AUGUSTUS trial showed that aspirin added to OAC and clopidogrel for 30 days, but not thereafter, resulted in fewer severe ischemic events. This finding emphasizes the relevance of early aspirin administration on ischemic benefit, also reflected in the current ESC guideline. However, because we consider the bleeding risk of TAT unacceptably high, we propose to use a short course of DAPT (omitting OAC for 1 month). There is evidence from the BRIDGE study that a short period of omitting OAC is safe in patients with AF. In this study, these patients are treated with DAPT, which also prevents stroke, albeit not as effective as OAC. This temporary interruption of OAC will allow aspirin treatment in the first month post-PCI where the risk of both bleeding and stent thrombosis is greatest. The WOEST 3 trial is a multicentre, open-label, randomised controlled trial investigating the safety and efficacy of one month DAPT compared to guideline-directed therapy consisting of OAC and P2Y12 inhibitor combined with aspirin up to 30 days. We hypothesise that the use of short course DAPT is superior in bleeding and non-inferior in preventing ischemic events. The primary safety endpoint is major or clinically relevant non-major bleeding as defined by the ISTH at 6 weeks after PCI. The primary efficacy endpoint is a composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis at 6 weeks after PCI.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,000

participants targeted

Target at P75+ for phase_4

Timeline
20mo left

Started Jan 2023

Longer than P75 for phase_4

Geographic Reach
2 countries

20 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress68%
Jan 2023Dec 2027

First Submitted

Initial submission to the registry

June 16, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 18, 2020

Completed
2.6 years until next milestone

Study Start

First participant enrolled

January 11, 2023

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

December 15, 2023

Status Verified

December 1, 2023

Enrollment Period

4.7 years

First QC Date

June 16, 2020

Last Update Submit

December 14, 2023

Conditions

Keywords

Acute Coronary SyndromeMyocardial InfarctionAtrial FibrillationAtrial FlutterSTEMI - ST Elevation Myocardial InfarctionNSTEMI - Non-ST Segment Elevation MIOral AnticoagulantNOAC - Novel Oral AnticoagulantDOAC - Direct Oral AnticoagulantDAPT - Dual Antiplatelet TherapyAntithrombotic TherapyDual TherapyTriple TherapyBleedingThrombosisStrokeStent ThrombosisSystemic EmbolismPercutaneous coronary interventionCoronary artery disease

Outcome Measures

Primary Outcomes (2)

  • Primary safety endpoint

    Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis

    6 weeks

  • Primary efficacy endpoint

    Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis

    6 weeks

Secondary Outcomes (11)

  • Bleeding complications

    6 months

  • Thrombotic complications

    6 months

  • Net clinical benefit

    6 weeks, 3 months, 6 months

  • Clinical symptom severity

    6 weeks, 3 months, 6 months

  • All-cause death

    6 weeks, 3 months, 6 months

  • +6 more secondary outcomes

Other Outcomes (1)

  • Quality of life as assessed by the EuroQol-5D-5L questionnaire

    6 weeks, 3 months, 6 months

Study Arms (2)

First month DAPT

ACTIVE COMPARATOR

30-day DAPT (aspirin + P2Y12 inhibitor). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor. Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines. NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.

Drug: 30-day DAPT

Guideline-directed therapy

ACTIVE COMPARATOR

Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor. Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines. NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.

Drug: Guideline-directed therapy

Interventions

DAPT (aspirin + P2Y12 inhibitor) during the first 30 days following PCI. After 30 days, all patients will be treated with edoxaban and a P2Y12 inhibitor.

First month DAPT

Guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)

Guideline-directed therapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients ≥ 18 years
  • Undergoing successful PCI (either ACS or elective PCI)
  • History of or newly diagnosed (\<72 hours after PCI/ACS) atrial fibrillation or flutter with a long-term (≥ 1 year) indication for OAC

You may not qualify if:

  • Contra indication to edoxaban, aspirin or all P2Y12 inhibitors
  • Current indication for OAC besides atrial fibrillation/flutter (e.g. venous thromboembolism)
  • \<12 months after any stroke
  • CHADSVASc score ≥7
  • Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2)
  • Mechanical heart valve prosthesis
  • Intracardiac thrombus or apical aneurysm requiring OAC
  • Poor LV function (LVEF \<30%) with proven slow-flow
  • History of intracranial haemorrhage
  • Active bleeding on randomization
  • History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding, unless the causative factor has been permanently resolved
  • Recent (\<1 month) gastrointestinal haemorrhage, unless the causative factor has been permanently resolved.
  • Known coagulopathy
  • Severe anaemia requiring blood transfusion or thrombocytopenia \<50 × 109/L
  • BMI \>40 or bariatric surgery
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

ASZ Aalst

Aalst, Belgium

RECRUITING

UZ Antwerpen

Antwerp, Belgium

RECRUITING

Imelda Ziekenhuis

Bonheiden, Belgium

RECRUITING

UZ Brussel

Brussels, Belgium

RECRUITING

Ziekenhuis Oost-Limburg

Genk, Belgium

RECRUITING

AZ Maria Middelares Gent

Ghent, Belgium

RECRUITING

Jan Yperman

Ieper, Belgium

NOT YET RECRUITING

AZ Groeninge

Kortrijk, Belgium

RECRUITING

UZ Leuven

Leuven, Belgium

RECRUITING

AZ Delta

Roeselare, Belgium

RECRUITING

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

RECRUITING

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

OLVG

Amsterdam, Netherlands

RECRUITING

Catharina Ziekenhuis

Eindhoven, Netherlands

RECRUITING

Treant Zorggroep

Emmen, Netherlands

RECRUITING

Zuyderland Ziekenhuis

Heerlen, Netherlands

NOT YET RECRUITING

Tergooi MC

Hilversum, Netherlands

RECRUITING

St. Antonius Hospital

Nieuwegein, Netherlands

RECRUITING

Hagaziekenhuis

The Hague, Netherlands

RECRUITING

Elisabeth Tweesteden Ziekenhuis

Tilburg, Netherlands

RECRUITING

Related Publications (1)

  • Verburg A, Bor WL, Kucuk IT, Henriques JPS, Vink MA, Ruifrok WT, Plomp J, Heestermans TACM, Schotborgh CE, Vlaar PJ, Magro M, Rikken SAOF, van den Broek WWA, van Mieghem CAG, Cornelis K, Rosseel L, Dujardin KS, Vandeloo B, Vandendriessche T, Ferdinande B, van 't Hof AWJ, Tijssen JGP, Limbruno U, De Caterina R, Rubboli A, Angiolillo DJ, Adriaenssens T, Dewilde W, Ten Berg JM. Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial. EuroIntervention. 2024 Jul 15;20(14):e898-e904. doi: 10.4244/EIJ-D-24-00100.

MeSH Terms

Conditions

Acute Coronary SyndromeMyocardial InfarctionAtrial FibrillationAtrial FlutterST Elevation Myocardial InfarctionNon-ST Elevated Myocardial InfarctionHemorrhageStrokeEmbolismCoronary Artery DiseaseThrombosis

Interventions

2'-deoxythymidylyl-(3'-5')-2'-deoxyadenosine

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisArrhythmias, CardiacCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesEmbolism and ThrombosisCoronary DiseaseArteriosclerosisArterial Occlusive Diseases

Study Officials

  • Jurriën M ten Berg, Prof, MD

    St. Antonius Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: The study is designed as a multicentre open label randomized controlled superiority trial with regards to safety and non-inferiority trial with regards to efficacy. Participating study centres will enrol patients undergoing PCI who have previously or newly diagnosed AF and indication for NOAC. As soon as possible, but within 72 hours after PCI, patients will be randomized 1:1 to either * 30 days DAPT (asprin + P2Y12 inhibitor), followed by guideline-directed therapy (edoxaban + P2Y12 inhibitor) * Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor dr.

Study Record Dates

First Submitted

June 16, 2020

First Posted

June 18, 2020

Study Start

January 11, 2023

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

December 15, 2023

Record last verified: 2023-12

Data Sharing

IPD Sharing
Will share

Will individual participant data be available? Yes What data in particular will be shared? Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices). What other documents will be available? Study Protocol, informed consent form, clinical study report When will data be available (start and end dates)? Within 1 year following article publication. End date to be determined. With whom? Researchers who provide a methodologically sound proposal. For what types of analyses? To achieve aims in the approved proposal. By what mechanism will data be made available? Proposals should be directed to as.verburg@antoniusziekenhuis.nl. To gain access, data requestors will need to sign a data access agreement.

Shared Documents
STUDY PROTOCOL, ICF, CSR
Time Frame
Within 1 year following article publication. End date to be determined.
Access Criteria
Researchers who provide a methodologically sound proposal.

Locations