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

Official title

Avoiding Risks of Thrombosis and Bleeding in Surgery (ARTS) Trial: An International Randomised Controlled Trial Evaluating Apixaban Versus No Anticoagulation in Patients Undergoing General Abdominal, Gynecologic and Urologic Surgery

Overview

Avoiding Risks of Thrombosis and bleeding in Surgery (ARTS) trial is a pragmatic, international, multicenter, randomized controlled open label trial comparing a direct oral anticoagulant (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 venous thromboembolism (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.

Interventions

• Drug Apixaban 2.5 MG
  To evaluate the benefits and risks of thromboprophylaxis with oral factor Xa inhibitor Apixaban compared to No anticoagulation

Primary outcome measures

• Incidence composite outcome of venous thromboembolism (VTE) [Time frame: 90 days]

Secondary outcome measures (2)

• Incidence of symptomatic DVT [Time frame: 90 days]
• Incidence of symptomatic PE [Time frame: 90 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Finland · 1 center

• Helsinki University Hospital — Helsinki

Identifiers

NCT: NCT06523959 · CLUE-ARTS-2023 · 2023-508147-43-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗