Clinical trial NCT06523959: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Venous Thromboembolism
Bleeding
Keywords: angioembolisation
apixaban
bleeding
complications
deep vein thrombosis
direct oral anticoagulant
DOAC
embolisation
evidence-based medicine
gynecology
hemoglobin
hemorrhage
mortality
open label
postoperative
pragmatic
pulmonary embolism
randomized trial
RCT
re-operation
reintervention
surgery
thrombosis
thromboprophylaxis
transfusion
urology
venous thromboembolism
VTE
Lead sponsor: Clinical Urology and Epidemiology Working Group
Sponsor class: OTHER_GOV
Collaborators: name: Helsinki University Central Hospital
name: University of Helsinki
name: University College, London
name: Population Health Research Institute
name: Tabriz University of Medical Sciences
name: Tampere University Hospital
name: Turku University Hospital
name: Oulu University Hospital
name: North Karelia Central Hospital
name: Albany Medical College
name: PaijatHame Central Hospital
First posted: 2024-07-29
Enrollment: 5436
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a pragmatic randomized controlled, parallel group, open-label trial with a 1:1 randomization (block randomization) ratio.
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Incidence composite outcome of venous thromboembolism (VTE)
timeFrame: 90 days
Secondary outcomes:
measure: Incidence of symptomatic DVT
timeFrame: 90 days
measure: Incidence of symptomatic PE
timeFrame: 90 days
Other outcomes:
measure: Incidence of composite endpoint for major bleeding
timeFrame: 90 days
measure: Incidence of re-intervention or endovascular embolization to stop bleeding
timeFrame: 90 days
measure: Incidence of composite outcome of VTE
timeFrame: 30 days
measure: Incidence of composite endpoint for major bleeding
timeFrame: 30 days
measure: Incidence of re-intervention or endovascular embolization to stop bleeding
timeFrame: 30 days
measure: Incidence of symptomatic non-fatal PE
timeFrame: 90 days
measure: Incidence of symptomatic fatal PE
timeFrame: 90 days
measure: Incidence of bleeding leading to a postoperative hemoglobin <70 g/L
timeFrame: 90 days
measure: Incidence of transfusion of ≥1 unit of red blood cells
timeFrame: 90 days
measure: Incidence of bleeding that was judged to be the immediate cause of death
timeFrame: 90 days
measure: Incidence of bleeding requiring re-intervention to stop bleeding
timeFrame: 90 days
measure: Incidence of bleeding requiring endovascular embolization to stop bleeding
timeFrame: 90 days
measure: Overall mortality
timeFrame: 90 days
measure: Incidence of SUSARs potentially related to the study drug (apixaban)
timeFrame: 90 days
measure: Incidence of Serious Adverse Events (SAEs), any
timeFrame: 90 days
measure: Incidence of any potentially drug-related SAEs (serious), cardiac complications, cerebral complications, infectious complications, admittance to intensive care, reoperation or other intervention for other reason than bleeding and other complication
timeFrame: 90 days
measure: Incidence of critical organ bleeding
timeFrame: 90 days
measure: Cost-effectiveness of DOAC administration
timeFrame: 90 days
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital
Study officials:
affiliation: University of Helsinki and Helsinki University Hospital
name: Kari AO Tikkinen, Professor
role: PRINCIPAL_INVESTIGATOR
References: