Hip Fracture Surgery, Cardiovascular Prevention, Venous Thromboembolism (VTE)
Conditions
Keywords
rivaroxaban, acetylsalicylic acid, cardiovascular prevention, hip fracture surgery, myocardial injury, venous thromboembolism (VTE)
Brief summary
A third of patients undergoing surgery for a hip fracture develop a myocardial injury (i.e., an elevated troponin measurement), and these patients are at substantial risk of death and morbidity. Current prophylaxis strategies focus on preventing venous thromboembolism (VTE); however, arterial events are more common and carry a poor prognosis. The association of acetylsalicylic acid (ASA) 75-100 mg once daily and rivaroxaban 2.5 mg twice a day (the regimen used in the COMPASS trial) might prevent both VTE and arterial cardiovascular events. Among patients who have undergone hip fracture surgery and have evidence of myocardial injury, to explore the feasibility of a randomized controlled trial (RCT) comparing rivaroxaban 2.5 mg twice daily + low-dose ASA (75-100 mg) for 90 days, with standard VTE thromboprophylaxis for 30 days, for prevention of major cardiovascular events. The HIPSTER-Pilot is a multicenter, international, open-label, pilot RCT with blinded outcome adjudication. A total of 100 participants aged ≥45 years who received hip fracture surgery and experienced a myocardial injury will be randomized to receive either rivaroxaban 2.5 mg twice daily plus ASA 75-100 mg daily for 90 days or standard VTE prophylaxis with an anticoagulant for 30 days. The primary feasibility outcome will be the recruitment rate. Other feasibility measures include completeness of follow-up and adherence to the treatment. Exploratory clinical outcomes will be assessed. This pilot trial will provide information on the feasibility of conducting a larger RCT to evaluate the efficacy and safety of the COMPASS regimen for preventing arterial and venous thrombotic events after hip fracture surgery in patients who have had myocardial injury. The results of this feasibility study will inform the design of the full-scale trial.
Interventions
rivaroxaban 2.5 mg orally BID and ASA 75-100 mg OD for 90 days
Enoxaparin: 40 mg subcutaneously OD (or 30 mg subcutaneously BID); Dalteparin: 5000 IU subcutaneously OD (or alternative dosing based on institutional protocol); Tinzaparin: 4500 IU subcutaneous OD
DRUGFondaparinux
2.5 mg subcutaneously OD
Rivaroxaban 10 mg OD or apixaban 2.5 mg BID, started after surgery or after a period of LMWH.
Sponsors
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
International Network of VENous Thromboembolism Clinical Research Networks
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Statisticians.
Intervention model description
A total of 100 participants aged ≥45 years who received hip fracture surgery and experienced a myocardial injury will be randomized to receive either rivaroxaban 2.5 mg twice daily plus ASA 75-100 mg daily for 90 days or standard VTE prophylaxis with an anticoagulant for \ 30 days, as per the standard of care.
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥45 years, received surgery for a hip fracture due to a low-energy mechanism, and myocardial injury (i.e., an elevated troponin measurement).
Exclusion criteria
* Centers in which standard of care for VTE prophylaxis after hip fractures is ASA, alone or in combination with other drugs; patients with GFR \<15mL/min; patients with drug interactions and conditions that prevent the use of the standard of care or intervention \[Known allergy to the study drugs; pregnancy; an indication for anticoagulation, for dual antiplatelet therapy, for a P2Y12 inhibitor; already on rivaroxaban 2.5 mg twice daily + ASA before the fracture; bleeding diathesis that in the judgment of the investigator precludes the use of anticoagulant prophylaxis; history of significant hepatic disease (Child-Pugh B or C, see supplementary material) or any other condition that, in the judgment of the investigator, precludes the use of rivaroxaban; concomitant use of drugs that are strong inhibitors or strong inducers of P-glycoprotein (P-gp, e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus \[HIV\]-protease inhibitors, such as ritonavir) and/or Cytochrome P450 3A4 (CYP3A4)\]; expected requirement for major surgery post-arthroplasty within 90 days; women Persons of childbearing potential who are not abstinent or do not use appropriate contraception or are breast-feeding; unable or unwilling to provide consent; previous participation in the HIPSTER trial; participation in another anticoagulant or antiplatelet study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment rate | Through study completion, an average of 1 year. | Number of patients recruited per month per site |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FUP completion | assessed at 30 and 90 days | Proportion of patients with a complete follow up |
| Treatment adherence | 30 and 90 days for the intervention, pre-specified treatment duration as per standard of care for the control. | Proportion of number of days on treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clinically relevant nonmajor bleeding | From randomization to 90 days post-randomization. | — |
| Minor bleeding | From randomization to 90 days post-randomization. | — |
| Cardiovascular mortality | From randomization to 90 days post-randomization. | — |
| Quality of life (EQ-5D-5L) | 90 days | Measured with EQ-5D-5L |
| Hospitalizations | From randomization to 90-days post randomization. | The length of stay and re-hospitalizations as measures of resource utilization. |
| Bleeding independently associated with mortality after non-cardiac surgery (BIMS) | From randomization to 90 days post-randomization. | Bleeding leading to a postoperative haemoglobin \<70 g/L, transfusion of 1 unit of red blood cells, or bleeding that was judged to be the cause of death. |
| all-cause mortality, MI, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic objectively confirmted VTE | From randomization to 90 days post-randomization. | Composite. Also each individual component will be assessed. |
| Major bleeding events | From randomization to 90 days post-randomization. | Major bleeding events as defined by the ISTH. |
Countries
Canada, Italy
Contacts
Primary ContactFederico Germini, Doctor of Medicine
Backup ContactBambie Levoy-Jones, Honours Bachelor of Science
Outcome results
None listed