Avoiding Risks of Thrombosis and bleeding in Surgery (ARTS) trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

HUS-yhtymae

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

31 May 2024 → ongoing

Decision date (initial)

2024-04-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Helsinki and Uusimaa Hospital District · Turku University Hospital · Finnish Medical Foundation · Tampere University Hospital · Oulu University Hospital · Sigrid Jusélius Foundation · Academy of Finland

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy, Safety

To evaluate the benefits and risks of thromboprophylaxis with apixaban (oral factor Xa inhibitor) DOAC therapy (with standard of care mechanical thromboprophylaxis) compared with no anticoagulant (with standard of care mechanical thromboprophylaxis) for patients undergoing urologic, gynecologic, and general abdominal surgery procedures, where patients are at sufficiently similar (and not high) risks of VTE and bleeding such that the net impact of pharmacological thromboprophylaxis remains uncertain

Conditions and MedDRA coding

Venous thromboembolism (in surgical patients)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Informed consent
2. Adult patients (≥18 years) at screening
3. Undergoing abdominal or pelvic surgery at similar (and not high) risk of VTE and bleeding

Exclusion criteria 20

1. Inability to provide informed consent
2. Patient with active bleeding/hemorrhage during the last 6 months if not expected to be treated by surgery planned
3. 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
4. Anticoagulant treatment, antiplatelet treatment or omega-3 dietary supplement during previous 7 days preceding surgery and/or requiring within 30 days post-surgery
5. Patient who had during previous 6 months or are expected require within 30 days post-surgery chemotherapy/ radiation or hormone therapy for cancer
6. Known thrombophilia
7. Known bleeding disorder
8. Substantial liver impairment (for instance INR 1.4 or more during last 60 days)
9. eGRF <30 mL/min/1.73 m2
10. Platelet count <100 × 109/L (that is, 100 000 mg/L)
11. Hb <90 g/L (that is, <9 g/dL)
12. ALT >2 times upper limit of normal
13. Known allergy to apixaban
14. 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
15. Concomitant procedures with high risk of VTE/bleeding
16. Previous VTE
17. Pregnant or breast-feeding female patients
18. 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
19. Previous randomization in this trial
20. Any reason why, in the opinion of the investigator(s), the patient should not participate

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence composite outcome of venous thromboembolism (VTE), defined as symptomatic deep vein thrombosis (DVT), or symptomatic non-fatal or fatal pulmonary embolism (PE) (at 90 days)

Secondary endpoints 19

1. Incidence of symptomatic DVT (at 90 days)
2. Incidence of symptomatic non-fatal or fatal PE (at 90 days)
3. Safety outcome 1. Incidence of composite endpoint for major bleeding, defined as bleeding leading to a postoperative hemoglobin <70 g/L, transfusion of ≥1 unit of red blood cells, or bleeding that was judged to be the immediate cause of death (at 90 days)
4. Safety outcome 2. Incidence of bleeding requiring re-intervention or endovascular embolization to stop bleeding (at 90 days)
5. Other/Tertiary Outcome 1. Incidence of composite outcome of VTE, defined as symptomatic DVT, or symptomatic non-fatal or fatal PE (at 30 days)
6. Other/Tertiary Outcome 2. Incidence of composite endpoint for major bleeding, defined as bleeding leading to a postoperative hemoglobin <70 g/L, transfusion of ≥1 unit of red blood cells, or bleeding that was judged to be the immediate cause of death (at 30 days)
7. Other/Tertiary Outcome 3. Incidence of bleeding requiring re-intervention or endovascular embolization to stop bleeding (at 30 days)
8. Other/Tertiary Outcome 4. Incidence of symptomatic non-fatal PE (at 90 days)
9. Other/Tertiary Outcome 5. Incidence of symptomatic fatal PE (at 90 days)
10. Other/Tertiary Outcome 6. Incidence of bleeding leading to a postoperative hemoglobin <70 g/L (at 90 days)
11. Other/Tertiary Outcome 7. Incidence of transfusion of ≥1 unit of red blood cells (at 90 days)
12. Other/Tertiary Outcome 8. Incidence of bleeding that was judged to be the immediate cause of death (at 90 days)
13. Other/Tertiary Outcome 9. Incidence of bleeding requiring re-intervention to stop bleeding (at 90 days)
14. Other/Tertiary Outcome 10. Incidence of bleeding requiring endovascular embolization to stop bleeding (at 90 days)
15. Other/Tertiary Outcome 11. Overall mortality (at 90 days)
16. Other/Tertiary Outcome 12. Suspected unexpected serious adverse reactions (SUSARs) potentially related to the study drug (apixaban) (at 90 days)
17. Other/Tertiary Outcome 13. Serious Adverse Events (SAEs), any (at 90 days) • Any potentially drug-related SAEs, cardiac complications (serious), cerebral complications (serious), infectious complications (serious), admittance to intensive care, reoperation or other intervention for other reason than bleeding and other complication, details available at the CRF
18. Other/Tertiary Outcome 14. Critical organ bleeding (at 90 days) • Intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intra-articular, and/or intramuscular bleeding with compartment syndrome
19. Other/Tertiary Outcome 15. Cost-effectiveness of DOAC administration (at 90 days)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

HUS-yhtymae

Sponsor organisation

HUS-yhtymae

Address

Haartmaninkatu 4

City

Helsinki

Postcode

00290

Country

Finland

Scientific contact point

Organisation

HUS Helsinki University Hospital

Contact name

Vatsakeskus/ ARTS Project office

Public contact point

Organisation

HUS Helsinki University Hospital

Contact name

Vatsakeskus/ ARTS Project office

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications