Clinical trial NCT04753372: Rivaroxaban Plus Aspirin in Patients With Chronic Coronary Syndrome and High Ischemic Risk
Official title: Effectiveness and Safety of Low Dose Rivaroxaban Plus Aspirin in Patients With Chronic Coronary Syndrome and High Ischemic Risk
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease (CAD)
Peripheral Arterial Disease (PAD)
Keywords: Coronary Artery Disease (CAD)
peripheral arterial disease (PAD)
high ischemic risk
Lead sponsor: Maatschap Cardiologie Zwolle
Sponsor class: OTHER
Collaborators: name: Diagram B.V.
First posted: 2021-02-15
Enrollment: 645
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Female and male patients with a diagnosis of CCS and/or symptomatic PAD will be enrolled in the (outpatient) clinic within 4 weeks after the decision for treatment with rivaroxaban 2x2.5mg plus ASA (75-100mg) has been made by the investigator (according to label (indicated for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events)) and who consent to participate in the study.

Brief summary: Registry to describe the impact in terms of effectiveness and safety of the combination treatment of rivaroxaban 2.5 mg twice daily with aspirin on clinical outcomes and practices in a real-life Dutch patient population that are at high risk of ischemic events.

Detailed description: This study is a national multicentre (\~15 sites), prospective, single-arm, observational study in patients treated with rivaroxaban 2.5mg bid on top of ASA75-100mg OD (N=1000). Female and male patients with a diagnosis of CCS and/or symptomatic PAD will be enrolled in the (outpatient) clinic after the decision for treatment with rivaroxaban 2.5mg bid, co-administered with acetylsalicylic acid has been made by the treating physician.

The primary effectiveness endpoint is a composite of:

* Major Adverse Cardiac Events (MACE including stroke, cardiovascular mortality and myocardial infarction)
* Clinically driven coronary, peripheral or carotid revascularization
* Stent thrombosis at one year

The primary safety endpoint is Major Bleeding at one year. These major bleeding complications are analysed according to the International Society on Thrombosis and Haemostasis (ISTH) criteria as a composite of fatal bleeding, symptomatic bleeding into a critical organ (such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome), bleeding causing a fall in haemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells.

The secondary endpoints will be:

* Occurrence (and date) of stroke
* Occurrence (and date) of myocardial infarction
* Occurrence (and date) of cardiovascular death
* Occurrence (and date) of coronary revascularization procedures (PCI, CABG).
* Occurrence (and date) of peripheral revascularization procedures.
* Occurrence (and date) of carotid revascularization procedures.
* Occurrence (and date) of minor bleeding complications (according to ISTH)

In addition, all bleeding events including minor bleedings according to ISTH definitions will be reported.

Eligibility criteria: Inclusion Criteria:

* Adult (≥18 years) patient.
* Diagnosis of CAD and/or PAD and high risk of ischemic events.

  * Patients at high risk of ischaemic events include the following:
  * CAD + PAD
  * CAD + Recurrent MI (Previous MI followed by second MI)
  * CAD + diabetes mellitus (all types)
  * CAD + chronic kidney disease with eGFR 30-59 ml/min/1.73 m2 (CKD-EPI formula)
  * CAD + heart failure (ejection fraction ≥30% - 50%) and New York Heart Association (NYHA) class I or II;)
  * CAD + CHA2DS2VaSc ≥ 3 (for men) or ≥ 4 (for women)
* Patients can only be enrolled in the study if the decision to treat with rivaroxaban plus ASA has been made by the treating physician in advance and independent of study inclusion, however within 4 weeks prior to study inclusion.
* Treatment according to local marketing authorization, with rivaroxaban 2.5 mg \[BID\] and 80mg ASA / 100mg Carbasalate calcium. Treatment of rivaroxaban started within 4 weeks prior or 4 weeks after study inclusion.
* Patients who are willing to participate in this study (signed informed consent).

Exclusion Criteria:

* Hypersensitivity/allergy and known contraindication to ASA/Carbasalate calcium or rivaroxaban
* Patients with recent major bleeding, active bleeding, or history with:

  * History of major clinical bleeding or known coagulopathy
  * History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke
  * Known severe liver dysfunction
* Patients that have received any organ transplant or await any organ transplant
* Patient with anemia (Hb \< 6.0 mmol/L)
* Patient with active malignancy
* Patients with ejection fraction \< 30% and/or New York Heart Association (NYHA) class III or IV
* Patients with eGFR \< 30 ml/min/1.73m2 or undergoing dialysis
* Patients with liver failure accompanied with coagulopathy ( incl. Child-Pugh B and C)
* Patients with concomitant use of other anticoagulants or antiplatelet drugs
* Pregnant or lactating female
* Patients currently participating in another investigational drug or drug-coated device study

Primary outcomes:
measure: Primary Outcome Measures
timeFrame: one year
Secondary outcomes:
measure: Secondary Outcome Measures
timeFrame: one year
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: OLVG
city: Arnhem
country: Netherlands
facility: Rijnstate hospital
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch hospital
city: Den Haag
country: Netherlands
facility: Haaglanden Medisch Centrum
city: Den Haag
country: Netherlands
facility: Hagaziekenhuis
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Heerlen
country: Netherlands
facility: Zuyderland Medical Center
city: Meppel
country: Netherlands
facility: Isala Klinieken, location Meppel
city: Nieuwegein
country: Netherlands
facility: St. Antonius hospital
city: Tilburg
country: Netherlands
facility: Elisabeth-Tweesteden hospital
city: Venlo
country: Netherlands
facility: VieCuri
city: Zwolle
country: Netherlands
facility: Isala hospital
Study officials:
affiliation: Isala
name: Rik Hermanides, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: