Dual Therapy With Dabigatran/Ticagrelor Versus Dual Therapy With Dabigatran/Clopidogrel in ACS Patients With Indication for NOAC Undergoing PCI (RE-DUAL PCI)

RE-DUAL PCI Real Life Registry Dual Therapy With Dabigatran/Ticagrelor Versus Dual Therapy With Dabigatran/Clopidogrel in ACS Patients With Indication for NOAC Undergoing PCI

A real world registry to compare dual therapy with Dabigatran/Ticagrelor to dual therapie with Dabigatran/Clopidogrel in patients with an indication for NOAC undergoing PCI in the setting of ACS. Hypothesis: Dual therapy with Dabigatran/Ticagrelor will be non-inferior in reducing the risk of bleeding compared to Dual therapy with Dabigatran/Clopidogrel (RE-DUAL PCI trial based) in patients with an indication for NOAC undergoing PCI in the setting of ACS. Thromboembolic events, stent thrombosis and death will be evaluated for estimation of events between both groups. Data will be pooled for this secondary endpoint with data from the upcoming WOEST-3 trial to compare both treatments.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction; Myocardial Ischemia; Coronary Artery Disease; Atrial Fibrillation
• Intervention / Treatment: Drug: Dabigatran + clopidogrel; Drug: Dabigatran + Ticagrelor

Detailed Description

The REDUAL PCI Registry will we be an open-label multicenter registry based randomised controlled trial (RBRCT) within the ZON-HR collaboration in 4 of the 6 centers in the Netherlands: Maastricht Universitair Medisch Centrum (Maastricht), Zuyderland (Heerlen and Sittard), Vie Curi (Venlo) and Radboud Medisch Centrum (Nijmegen). Isala (Zwolle) and Canisius Wilhelmina ziekenhuis (Nijmegen) will not be part of this study. This study is Investigator initiated with an unrestricted grant from Boehringer Ingelheim (subsidising party). This study is also to be noted as a Post Authorisation Safety Study (PASS). Patients 1000 patients with an indication for NOAC, who underwent successful PCI with Drug Eluting Stent (DES) in the setting of ACS will be included and randomised at each of the 4 centers of the ZON-HR. After randomisation, patients will be treated with Dual therapy with Dabigatran/Clopidogrel or with Dabigatran/ Ticagrelor. A total of 1000 patients in 4 centers will be included: 250 patients in each center. In each center inclusion and randomisation will be executed within 48 hours after PCI. Inclusions are expected to be done within 1 year. After inclusion of the interventional (Dual therapy with Dabigatran/Ticagrelor) and control group (Dual therapy with Dabigatran/Clopidogrel), follow-up of 1 year is planned.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Heerlen, Limburg, Netherlands, 6419PC
      • Recruiting
      • Zuyderland MC
      • Contact: Patty Winkler; Phone Number: +31 6 53368084; Email: p.winkler@zuyderland.nl
      • Sub-Investigator: Jasper Luijkx

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients having an indication for a NOAC or will start with oral anticoagulation (NOAC). Permanent, persistent or paroxysmal atrial fibrillation are eligible.
• PCI and successful stenting with DES for ACS (unstable angina pectoris, NSTEMI, STEMI)
• Written informed consent.

Exclusion Criteria:

• Patients unable or unwilling to comply with the protocol or with life expectancy shorter than the duration of the study
• Glomerular filtration rate < 30 ml/min
• Heart valve prosthesis (mechanical or biological)
• Cardiogenic shock

• Contra-indication for Dabigatran, Ticagrelor or Clopidogrel

  • Liver dysfunction (ALAT, ASAT, Alkaline phosphatase > 3x upper limit of normal) or liver disease (like hepatitis A, B, C)
  • Lesion or condition with a significant risk of serious bleeding, such as; current or recent gastrointestinal ulceration; malignant neoplasms with more bleeding risk; recent brain / spinal cord injury; recent surgery on the brain, spinal cord or eyes; recent or history of intracranial haemorrhage; oesophageal varices; arteriovenous malformations; vascular aneurysms; o severe intraspinal or intracerebral vascular abnormalities.
  • comedication with cyclosporine, itraconazole, ketoconazole (systemic) and glecaprevir / pibrentasvir, dronedarone, rifampicine, carbamazepine, St. Jan's wort or phenytoin o Comedication with tacrolimus is not recommended.
• Allergy to for Dabigatran, Ticagrelor or Clopidogrel
• Pregnancy
• Significant thrombocytopenia (platelet count < 50x10 9/L)
• Major bleeding according to BARC ≥3 within the past 6 months.
• Weight < 50 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Dabigatran/Clopidogrel; Patiënt receive standard care, with dabigatran + clopidogrel 75mg once daily up to 12 months.	Drug: Dabigatran + clopidogrel; Patiënt interventional treatment, with dabigatran + clopidogrel (plavix) 75mg once daily up to 12 months.
EXPERIMENTAL: Dabigatran/Ticagrelor; Patiënt receive standard care, with dabigatran + ticagrelor 90mg twice daily up to 12 months.	Drug: Dabigatran + Ticagrelor; Patiënt interventional treatment, with dabigatran + ticagrelor (Brilique) 90mg twice daily up to 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding	Bleeding defined as BARC bleeding score ≥2	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Infarction	Myocardial Infarction	12 months
Cerebrovascular accident	Cerebrovascular accident, ischemic of haemorrhagic	12 months
Systemic Embolic Complications	Systemic Embolic Complications	12 months
Death	Death	12 months
Combined endpoint of ischemic events	All secondary outcomes combined into one endpoint	12 months

Collaborators and Investigators

• Sponsor: Zuyderland Medisch Centrum
• Collaborators: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 23, 2020
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): July 1, 2023

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: December 23, 2020
• First Posted (ACTUAL): December 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Arrhythmias, Cardiac; Coronary Disease; Myocardial Infarction; Infarction; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Atrial Fibrillation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Ticagrelor; Clopidogrel; Dabigatran
• Other Study ID Numbers: METCZ20200196

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