Oral Blood Thinners for Hip Fracture

(HIP PRO Pilot Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Prism Schneider, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Calgary

Must not be taking: Blood thinners

Disqualifiers: Delayed presentation, Cancer, Bleeding disorder, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

As our Canadian population ages, hip fractures in these older adults are becoming very common. The best treatment for the majority of these injuries is urgent treatment with surgery. However, the hip fracture itself, the surgery required, and the immobility following these injuries are all risk factors for developing blood clots in the legs (deep vein thrombosis or DVT) and blood clots in the lungs (pulmonary embolism or PE). These complications are a common cause of death in patients with hip fractures and often result in prolonged medical treatment and hospital stays. Patients with hip fractures who require surgery are traditionally given injectable blood thinners to help prevent blood clots; however, these medications are costly, may not be tolerated well, and can be difficult to take, as prescribed. Oral blood thinning medications are being used more commonly, but it is unknown which of these medications is the most effective in preventing blood clots in patients after a hip fracture. Thrombelastography (TEG) technology uses a small sample of blood to evaluate a person's clotting ability. Our research has used TEG technology to evaluate blood clotting risk after hip fracture surgery and the investigators have found that platelets may play an important role in abnormal blood clotting after a hip fracture. The investigators have also shown that acetylsalicylic acid (ASA or Aspirin) may help reduce the abnormal platelet hyperactivity associated with blood clotting. This medication warrants investigation for blood clot prevention after hip fracture. The investigators propose to directly compare different oral medication regimens after hip fracture surgery, in order to determine which is safest and most effective in preventing blood clots. Our multi-disciplinary research team includes physicians, surgeons, and scientists with experience evaluating different medications for blood clot prevention. Our results will help determine the best medical treatment for preventing DVT and PE, which will benefit patients with hip fractures worldwide.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients who have been on certain blood thinners like Warfarin, DOACs, or chronic aspirin use in the three months before the hip fracture. It's best to discuss your current medications with the trial team to see if they affect your eligibility.

What data supports the effectiveness of the drugs Acetylsalicylic acid (ASA) and Rivaroxaban for hip fracture?

Research shows that both aspirin (ASA) and rivaroxaban are effective in preventing blood clots after surgeries like knee and hip replacements, which are similar to hip fracture surgeries. They have been found to prevent conditions like deep vein thrombosis (DVT) and pulmonary embolism (PE) without significantly increasing bleeding risks.

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Is it safe to use oral blood thinners like aspirin and rivaroxaban for hip fracture?

Research shows that both aspirin and rivaroxaban are generally safe for use in preventing blood clots after surgeries like hip and knee replacements. They do not significantly increase the risk of major bleeding or other serious side effects.

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How is the drug for hip fracture different from other treatments?

This treatment combines low-dose aspirin (acetylsalicylic acid, ASA) and rivaroxaban, both of which are anticoagulants (blood thinners) that help prevent blood clots. Unlike some other treatments, this combination is taken orally and is specifically studied for its effectiveness in preventing blood clots after hip fracture surgery, offering a potentially convenient and effective option.

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Eligibility Criteria

This trial is for adults aged 50 or older who have a hip fracture that needs surgery and got to the hospital within 24 hours of injury. They can be on low-dose anti-platelet therapy like aspirin. People with cancer-related fractures, those who can't follow up, took lots of blood thinners post-injury, or have certain bleeding/clotting disorders can't join.

Inclusion Criteria

I am currently taking a single anti-platelet medication.

Signed informed consent or surrogate consent to participate in study

I am 50 or older and need surgery for a hip fracture that happened within the last day.

Exclusion Criteria

I am under 50 years old.

I have been on blood thinners like Warfarin or aspirin for the last three months before my hip fracture.

I have a fracture around my hip replacement.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either rivaroxaban 10 mg daily or ASA 81 mg daily for 35 days post hip fracture surgery

5 weeks

Daily medication administration

Follow-up

Participants are monitored for safety and effectiveness, including VTE and bleeding complications, with assessments at various intervals

12 weeks

2-week, 4-week, 6-week, and 12-week follow-up visits

Long-term Follow-up

Participants are monitored for mortality and healthcare costs over a 12-month period

12 months

Participant Groups

The study compares oral blood thinners Rivaroxaban (10mg) and ASA (81mg) in preventing blood clots after hip fracture surgery. It aims to find out which one is safer and more effective using TEG technology to monitor clotting ability.

Group I: acetylsalicylic acid (ASA) 81mg daily Experimental Treatment 1 Intervention

acetylsalicylic acid (ASA) 81mg daily for 35 days post hip fracture surgery

Group II: Rivaroxaban 10mg Experimental Treatment 1 Intervention

Rivaroxaban 10mg daily for 35 days post hip fracture surgery

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Foothills Medical Centre Calgary, Canada

The Ottawa Hospital Ottawa, Canada

Royal Columbian Hospital New Westminster, Canada

Who Is Running the Clinical Trial?

University of Calgary Lead Sponsor

Canadian Institutes of Health Research (CIHR) Collaborator

References

1. Germany pubmed.ncbi.nlm.nih.gov

Aspirin versus Rivaroxaban to Prevent Venous Thromboembolism after Total Knee Arthroplasty: A Double-blinded, Randomized Controlled Trial. [2022] Objective  Aspirin (acetylsalicylic acid, ASA) and rivaroxaban are anticoagulants that have increased in popularity due to ease of use in the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA). The present study aimed to evaluate the efficacy of ASA compared with that of rivaroxaban on VTE prophylaxis in patients who underwent TKA. Method  Forty patients who had primary knee osteoarthritis and would undergo TKA were randomized into two groups. In total, 20 patients in the ASA group used oral aspirin, at a dose of 300 mg/day, for VTE prophylaxis after TKA, while 20 patients in the rivaroxaban group received oral rivaroxaban, at a dose of 10 mg/day. On days 4 and 14 after the operation, deep vein thrombosis (DVT) in the lower limbs on the operated side was detected through duplex ultrasonography. Other complications were recorded for 14 days. Results  There were no positive findings of DVT detected with duplex ultrasonography in the groups of patients, and the occurrence of pulmonary embolism was not observed. In total, 4 patients had subcutaneous ecchymosis on the fourth postoperative day (2 patients in the ASA group and 2 patients in the rivaroxaban group; p  = 1.0), and another 4 patients on the fourteenth postoperative day (1 patient in the ASA group and 3 patients in the rivaroxaban group; p  = 0.292). No cases of wound hematoma, major organ bleeding, wound infection, or reoperation were observed in the sample. Conclusion  Aspirin and rivaroxaban had comparable efficacy to prevent VTE, without increasing the incidence of wound complications and bleeding after TKA.

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rivaroxaban thromboprophylaxis after arthroplasty of the hip or knee: retrospective cohort study. [2023] Introduction Venous thromboembolism (VTE) is a potentially fatal complication of hip arthroplasty and knee arthroplasty. The National Institute for Health and Care Excellence recommend rivaroxaban for VTE prevention. Amid concerns over bleeding complications, the modified thromboprophylaxis policy of Chelsea and Westminster Hospital (CWH; London, UK) advises enoxaparin given after surgery in the inpatient setting followed by rivaroxaban upon hospital discharge. This retrospective study investigated the efficacy and safety of rivaroxaban in this novel, modified venous-prophylaxis regimen in a surgical orthopaedic cohort at CWH. Methods A total of 479 patients who received modified thromboprophylaxis treatment at CWH after hip arthroplasty or knee arthroplasty between April 2013 and October 2014 formed the study cohort. Seven outcomes based on efficacy and safety while undergoing treatment with rivaroxaban were investigated: symptomatic deep-vein thrombosis (DVT), pulmonary embolism (PE), death, stroke, myocardial infarction (MI), major bleeding episodes (MBEs) and non-major bleeding episodes (NMBEs). Median follow-up was 369 days. Fisher's exact and Mann-Whitney U-tests were adopted to identify associations with these outcomes. Results Prevalence of symptomatic PE, DVT, death, stroke and MI during treatment was zero. One (0.2%) MBE and nine (1.9%) NMBEs occurred. The MBE (a wound haematoma) required a return to theatre for aspiration. Off-treatment VTEs occurred in four (0.8%) patients after completion of a course of rivaroxaban, and were associated with known risk factors. Conclusions Rivaroxaban is an effective and safe anticoagulant for thromboprophylaxis after hip arthroplasty or knee arthroplasty if used in a modified regimen involving enoxaparin administered in the inpatient setting followed by rivaroxaban upon hospital discharge.

3. England pubmed.ncbi.nlm.nih.gov

Combination of Superficial and Deep Blocks with Rivaroxaban. [2015] Rivaroxaban is a new Xa inhibitor indicated for thromboprophylaxis in patients undergoing joint arthroplasty. This study was designed to assess the risk of major bleeding from the combination of either a single or a continuous deep, superficial, and plexus block and the use of rivaroxaban for thromboprophylaxis following joint arthroplasty.

4. Australia pubmed.ncbi.nlm.nih.gov

Comparison of the Efficacy and Safety of Aspirin and Rivaroxaban Following Enoxaparin Treatment for Prevention of Venous Thromboembolism after Hip Fracture Surgery. [2023] To compare the efficacy and safety of aspirin with rivaroxaban following treatment with enoxaparin for prevention of venous thromboembolism (VTE) after hip fracture surgery (HFS).

5. England pubmed.ncbi.nlm.nih.gov

Low-molecular-weight heparin versus rivaroxaban in orthopedic surgery. [2013] From the ORTHO-TEP registry on joint replacement arthroplasty (hip and knee) from Dresden, Germany, three periods of different prophylactic regimens have been compared. In the present paper, results from low-molecular-weight heparin and rivaroxaban have been analyzed, with rivaroxaban showing a benefit concerning both effect and side effects. Clinical end points are used, the results being in line with published data from randomized studies. Inclusion in the registry of consecutive patients is important to illustrate generalizability of results obtained in randomized trials. This review discusses the problem with using historical comparisons to draw firm conclusions.

6. Brazil pubmed.ncbi.nlm.nih.gov

Venous thromboembolism prophylaxis after total knee arthroplasty (TKA): aspirin vs. rivaroxaban. [2022] To compare the efficacy and safety of aspirin and rivaroxaban in preventing venous thromboembolism (VTE) after total knee arthroplasty (TKA).

7. New Zealand pubmed.ncbi.nlm.nih.gov

Therapeutic potential of rivaroxaban in the prevention of venous thromboembolism following hip and knee replacement surgery: a review of clinical trial data. [2022] Rivaroxaban (Bayer AG, Leverkusen, Germany) is a highly selective direct inhibitor of factor Xa. It has completed Phase III clinical trials evaluating its efficacy and safety against enoxaparin in the prophylaxis against venous thromboembolism (VTE) in orthopedic patients following primary total hip and total knee arthroplasty. Rivaroxaban has been extensively studied worldwide in 12,729 patients in the Regulation of Coagulation in Major Orthopedic Surgery Reducing the Risk of DVT and PE (RECORD) program. Pivotal clinical trials have demonstrated the superior efficacy in reducing total VTE in comparison with both the North American and European regimens of enoxaparin. Safety of the drug was found to be excellent, with no demonstrable cardiovascular or hepatic effects and no statistically significant increase in major bleeding. A pooled analysis of data collected on the patients from the four RECORD trials revealed rivaroxaban to be the first antithrombotic agent to demonstrate superiority over another antithrombotic (enoxaparin) in reducing symptomatic VTE and all-cause mortality. While there was a significant difference in the composite safety endpoint of major and clinically relevant nonmajor bleeding in the pooled analysis with the use of rivaroxaban compared with enoxaparin, there was no significant difference in major bleeding or in any other bleeding.

8. England pubmed.ncbi.nlm.nih.gov

Rivaroxaban, a new, oral, direct factor Xa inhibitor for thromboprophylaxis after major joint arthroplasty. [2019] The new oral, antithrombotic drug rivaroxaban is a direct factor Xa inhibitor, which can restrict thrombin generation both in vitro and in vivo. It has a predictable dose-dependent pharmacokinetic and pharmacodynamic profile and is well tolerated. In patients undergoing total hip or knee arthroplasty, rivaroxaban, 10 mg once daily started 6 - 8 h after the operation, had a significantly better antithrombotic efficacy and a comparable safety when compared with enoxaparin. Furthermore in all studies performed the drug had no adverse influence on the liver function in comparison with enoxaparin. In conclusion, rivaroxaban is a potent and safe new compound for antithrombotic prophylaxis in orthopaedic surgery.

9. Belgium pubmed.ncbi.nlm.nih.gov

[Rivaroxaban (Xarelto): new anticoagulant inhibitor of factor Xa]. [2015] (Xarelto, Bayer Schering Pharma) is a new anticoagulant with a good oral bioavailability, acting as a potent, selective direct inhibitor of factor Xa. It is indicated in the prevention of venous thromboembolism in adult patients after total hip replacement or total knee replacement surgery. In four large clinical trials (RECORD), oral rivaroxaban was more effective than subcutaneous enoxaparin in preventing postoperative venous thromboembolism in patients undergoing such surgery, and this superior efficacy was achieved without significant increase in the incidence of major bleeding episodes. Rivaroxaban offers several advantages as compared with low-molecular-weight heparin preparations and oral coumarinic agents. Its use is easy with only one 10 mg tablet per day and does not require coagulation blood monitoring or dose adjustment. This promising new anticoagulant is currently evaluated in several clinical trials testing other potential indications, among which acute coronary syndrome and atrial fibrillation.

10. United States pubmed.ncbi.nlm.nih.gov

A systematic review on the effect of aspirin in the prevention of post-operative arterial thrombosis in patients undergoing total hip and total knee arthroplasty. [2018] Major surgery is associated with increased risk of venous thromboembolism (VTE), which is decreased by anticoagulant drugs. Evidence is growing that major surgery is associated with increased risk of arterial thrombosis (AT). With the aim of testing aspirin ability in reducing the risk of post-operative AT, we performed a systematic review of studies in which acetylsalicylic acid (ASA) was compared to anticoagulant drugs in VTE prophylaxis of patients undergoing total hip replacement (THR) or total knee replacement (TKR).