Apixaban for Venous thromboembolism

Inclusion criteria

• {"criterion_text":"- Informed consent"}
• {"criterion_text":"- Adult patients (≥18 years) at screening"}
• {"criterion_text":"- Undergoing abdominal or pelvic surgery at similar (and not high) risk of VTE and bleeding"}

Exclusion criteria

• {"criterion_text":"- Inability to provide informed consent"}
• {"criterion_text":"- Platelet count <100 × 109/L (that is, 100 000 mg/L)"}
• {"criterion_text":"- Hb <90 g/L (that is, <9 g/dL)"}
• {"criterion_text":"- ALT >2 times upper limit of normal"}
• {"criterion_text":"- Known allergy to apixaban"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Concomitant procedures with high risk of VTE/bleeding"}
• {"criterion_text":"- Previous VTE"}
• {"criterion_text":"- Pregnant or breast-feeding female patients"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Previous randomization in this trial"}
• {"criterion_text":"- Patient with active bleeding/hemorrhage during the last 6 months if not expected to be treated by surgery planned"}
• {"criterion_text":"- Any reason why, in the opinion of the investigator(s), the patient should not participate"}
• {"criterion_text":"- Lesion or condition if considered a significant risk factor for major bleeding \ta) 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"}
• {"criterion_text":"- Anticoagulant treatment, antiplatelet treatment or omega-3 dietary supplement during previous 7 days preceding surgery and/or requiring within 30 days post-surgery"}
• {"criterion_text":"- Patient who had during previous 6 months or are expected require within 30 days post-surgery chemotherapy/ radiation or hormone therapy for cancer"}
• {"criterion_text":"- Known thrombophilia"}
• {"criterion_text":"- Known bleeding disorder"}
• {"criterion_text":"- Substantial liver impairment (for instance INR 1.4 or more during last 60 days)"}
• {"criterion_text":"- eGRF <30 mL/min/1.73 m2"}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Incidence measured at 90 days; composite defined as symptomatic DVT or symptomatic non-fatal or fatal PE."}

Secondary endpoints

• {"endpoint_text":"- Incidence of symptomatic DVT (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of symptomatic deep vein thrombosis."}
• {"endpoint_text":"- Incidence of symptomatic non-fatal or fatal PE (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of symptomatic non-fatal or fatal pulmonary embolism."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Incidence measured at 90 days; major bleeding composite defined as postoperative Hb <70 g/L, transfusion ≥1 unit RBCs, or bleeding judged immediate cause of death."}
• {"endpoint_text":"- Safety outcome 2. Incidence of bleeding requiring re-intervention or endovascular embolization to stop bleeding (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of bleeding requiring re-intervention or endovascular embolization."}
• {"endpoint_text":"- Other/Tertiary Outcome 1. Incidence of composite outcome of VTE, defined as symptomatic DVT, or symptomatic non-fatal or fatal PE (at 30 days)","definition_or_measurement_approach":"Incidence measured at 30 days of composite VTE (symptomatic DVT or symptomatic non-fatal/fatal PE)."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Incidence measured at 30 days using same major bleeding composite definition."}
• {"endpoint_text":"- Other/Tertiary Outcome 3. Incidence of bleeding requiring re-intervention or endovascular embolization to stop bleeding (at 30 days)","definition_or_measurement_approach":"Incidence measured at 30 days of bleeding requiring re-intervention or endovascular embolization."}
• {"endpoint_text":"- Other/Tertiary Outcome 4. Incidence of symptomatic non-fatal PE (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of symptomatic non-fatal pulmonary embolism."}
• {"endpoint_text":"- Other/Tertiary Outcome 5. Incidence of symptomatic fatal PE (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of symptomatic fatal pulmonary embolism."}
• {"endpoint_text":"- Other/Tertiary Outcome 6. Incidence of bleeding leading to a postoperative hemoglobin <70 g/L (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of bleeding leading to postoperative Hb <70 g/L."}
• {"endpoint_text":"- Other/Tertiary Outcome 7. Incidence of transfusion of ≥1 unit of red blood cells (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of transfusion of ≥1 unit RBCs."}
• {"endpoint_text":"- Other/Tertiary Outcome 8. Incidence of bleeding that was judged to be the immediate cause of death (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of bleeding judged to be immediate cause of death."}
• {"endpoint_text":"- Other/Tertiary Outcome 9. Incidence of bleeding requiring re-intervention to stop bleeding (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of bleeding requiring re-intervention."}
• {"endpoint_text":"- Other/Tertiary Outcome 10. Incidence of bleeding requiring endovascular embolization to stop bleeding (at 90 days)","definition_or_measurement_approach":"Incidence measured at 90 days of bleeding requiring endovascular embolization."}
• {"endpoint_text":"- Other/Tertiary Outcome 11. Overall mortality (at 90 days)","definition_or_measurement_approach":"All-cause mortality measured at 90 days."}
• {"endpoint_text":"- Other/Tertiary Outcome 12. Suspected unexpected serious adverse reactions (SUSARs) potentially related to the study drug (apixaban) (at 90 days)","definition_or_measurement_approach":"Incidence of SUSARs potentially related to apixaban measured at 90 days."}
• {"endpoint_text":"- Other/Tertiary Outcome 13. Serious Adverse Events (SAEs), any (at 90 days) •\tAny 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","definition_or_measurement_approach":"Incidence of any SAEs and specified categories measured at 90 days; details recorded in CRF."}
• {"endpoint_text":"- Other/Tertiary Outcome 14. Critical organ bleeding (at 90 days) •\tIntracranial, intraocular, intraspinal, pericardial, retroperitoneal, intra-articular, and/or intramuscular bleeding with compartment syndrome","definition_or_measurement_approach":"Incidence measured at 90 days of critical organ bleeding as specified."}
• {"endpoint_text":"- Other/Tertiary Outcome 15. Cost-effectiveness of DOAC administration (at 90 days)","definition_or_measurement_approach":"Cost-effectiveness analysis of DOAC administration evaluated at 90 days."}

Finland

Earliest CTIS Part Ii Submission Date

06-03-2024

Latest Decision Or Authorization Date

10-04-2024

Processing Time Days

35

Number Of Sites

13

Number Of Participants

1000

Primary sponsor

Full Name

HUS-yhtymae

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Finland

Third parties

• {"country":"","full_name":"Helsinki and Uusimaa Hospital District","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Turku University Hospital","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Finnish Medical Foundation","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Tampere University Hospital","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Oulu University Hospital","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Sigrid Jusélius Foundation","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Academy of Finland","duties_or_roles":"","organisation_type":""}