Avoiding Risks of Thrombosis and Bleeding in Surgery (ARTS) Trial

Phase 4

Recruiting

• Conditions: Venous Thromboembolism; Bleeding
• Interventions: Drug: Apixaban 2.5 MG

• Registration Number: NCT06523959
• Lead Sponsor: Clinical Urology and Epidemiology Working Group

Brief Summary

The ARTS trial is a pragmatic, international, multicenter, randomized controlled open label trial comparing a DOAC - oral factor Xa inhibitor apixaban - to no anticoagulant among 5,436 patients undergoing abdominal or pelvic surgery at sufficiently similar (and not high) risk of VTE and bleeding that the net impact - benefit or harm - of thromboprophylaxis remains in doubt.

Detailed Description

Deep vein thrombosis and pulmonary embolism - collectively known as venous thromboembolism VTE - and major bleeding are serious surgical complications leading to poorer patient-reported quality of life and mortality. Pharmacological thromboprophylaxis is an established strategy for reducing VTE risk but balancing it with increased bleeding, particularly after major surgery, poses challenges. Guidelines typically recommend pharmacological thromboprophylaxis for patients at higher, but not lower risk of VTE, without clearly defining procedure or patient selection. There is particular uncertainty regarding the balance of potential benefits and harms of pharmacological thromboprophylaxis in patients who are at a lower estimated risk of VTE postoperatively, in patients with a baseline VTE risk in the range of 2%. In these patients, the risk of major bleeding may be similar to or could potentially outweigh the relatively lower risk of VTE complications, such that the net clinical benefit of routine pharmacological thromboprophylaxis remains unclear.

"Avoiding Risks of Thrombosis and Bleeding in Surgery (ARTS)" is a large, randomized, multicenter study, comparing a direct oral anticoagulant (DOAC) called apixaban in patients undergoing abdominal and pelvic surgeries. Half of the 5436 patients will be randomized to receive apixaban after surgery for 28 days with standard of care mechanical prophylaxis - to a control group with no anticoagulation but with standard of care mechanical prophylaxis.

ARTS trial will be the first to compare anticoagulation with DOACs (apixaban) versus no anticoagulation in a population of urologic, gynecologic and abdominal surgical patients. Any of the possible outcomes of 1) A clear net benefit in favor of apixaban or 2) A clear net benefit to not using prophylaxis or 3) a sufficiently close tradeoff that predictive factors and patients' values and preferences regarding bleeding versus thrombosis determines the decision, will substantially enhance evidence-based peri-operative care.

Study Timeline

• Study Start: 2024-06-06
• Status Verified: 2024-07
• Study First Submitted: 2024-07-05
• Study First Submitted QC: 2024-07-23
• Last Update Submitted: 2024-07-23
• Study First Posted: 2024-07-29
• Last Update Posted: 2024-07-29
• Primary Completion: 2028-09-30
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 5436

Inclusion Criteria

• Informed consent provided
• Adult patients (≥18 years);
• Undergoing elective abdominal or pelvic surgery at similar (and not high) risk of VTE and bleeding

Exclusion Criteria

• Inability to provide informed consent

• Patient with active bleeding/hemorrhage during the last 6 months if not expected to be treated by surgery planned

• Lesion or condition if considered a significant risk factor for major bleeding

  a. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities

• Anticoagulant treatment, antiplatelet treatment or omega-3 dietary supplement during previous 7 days preceding surgery and/or requiring within 30 days post-surgery

• Patient who had during previous 6 months or are expected require within 30 days post-surgery chemotherapy/radiation or hormone therapy for cancer

• Known thrombophilia

• Known bleeding disorder

• Substantial liver impairment (for instance INR 1.4 or more during last 60 days)

• eGRF <30 mL/min/1.73 m2

• Platelet count <100 × 109/L (that is, 100 000 mg/L)

• Hb <90 g/L (that is, <9 g/dL)

• ALT >2 × upper limit of normal

• Known allergy to apixaban

• Taking strong inhibitors or inductors of both CYP 3A4 and P-glycoprotein, such as anti-seizure medications (e.g. phenytoin, fosphenytoin, carbamazepine), azole-antimycotics (e.g. ketoconazole, itraconazole), HIV-protease inhibitors (e.g. ritonavir, indinavir) and rifampicin

• Concomitant procedures with high risk of VTE/bleeding

• Previous VTE

• Pregnant or breast-feeding female patients

• Female participants who have had periods in the last 12 months and who are not using highly reliable contraception: (i) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); ii) progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); iii) intrauterine device (IUD); iv) intrauterine hormone-releasing system (IUS); v) bilateral tubal occlusion; vi) vasectomized partner; and vii) sexual abstinence from heterosexual intercourse during the entire period of risk associated with the study treatments

• Previous randomization in this trial

• Any reason why, in the opinion of the investigator(s), the patient should not participate

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apixaban	Apixaban 2.5 MG	Apixaban 2.5mg (i.e Eliquis® 2,5mg tablet) orally twice daily for 28 days (with standard of care mechanical prophylaxis)

Primary Outcome Measures

Name	Time	Method
Incidence composite outcome of venous thromboembolism (VTE)	90 days	Defined as symptomatic deep vein thrombosis (DVT), or symptomatic non-fatal or fatal pulmonary embolism (PE)

Secondary Outcome Measures

Name	Time	Method
Incidence of symptomatic PE	90 days	Defined as symptomatic non-fatal of fatal pulmonary embolism (PE)
Incidence of symptomatic DVT	90 days	Defined as symptomatic deep vein thrombosis

Trial Locations

Locations (1)

Helsinki University Hospital; 🇫🇮 Helsinki, Finland