Hip Fracture SurgeryPhase 3HIPSTER-PilotNCT07228663
Hip Fracture Surgery Arterial and Venous Thrombotic Events Prevention
A Phase 3 study testing rivaroxaban and ASA, Low-molecular weight heparin and Fondaparinux in people with Hip Fracture Surgery and Cardiovascular Prevention, run by McMaster University at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Hip Fracture Surgery, Cardiovascular Prevention, Venous Thromboembolism (VTE)
- What is being tested?
- rivaroxaban and ASA, Low-molecular weight heparin and Fondaparinux
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Dec 2025to 1 Dec 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥45 years, received surgery for a hip fracture due to a low-energy mechanism, and myocardial injury (i.e., an elevated troponin measurement).
Who cannot join
- 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.
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
Canada2 sites
St.Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
James Douketis, Doctor of Medicine, 905-521-6178, jdouket@mcmaster.ca
James Douketis, Doctor of Medicine
Juravinski Hospital
Hamilton, Ontario, L8V 1C3
Flavia Kessler Borges, Doctor of Medicine, 905-527-4322 ext. 40654, kesslerf@mcmaster.ca
Flavia Kessler Borges, Doctor of Medicine
Italy1 site
Humanitas Research Hospital
Milan
Corrado Lodigiani, Doctor of Medicine, +39 0282244656, corrado.lodigiani@humanitas.it
Corrado Lodigiani, Doctor of Medicine
About this study
Official title: Rivaroxaban Plus Acetylsalicylic Acid Versus Standard of Care for Arterial and Venous Cardiovascular Prevention After Hip Fracture Surgery in Patients With Myocardial Injury: a Pilot Randomized Trial
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.
- Being tested
- rivaroxaban and ASA, Low-molecular weight heparin, Fondaparinux, Direct Oral Anticoagulant (DOAC)
- Keywords
- rivaroxaban, acetylsalicylic acid, cardiovascular prevention, hip fracture surgery, myocardial injury, venous thromboembolism (VTE)
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rivaroxaban and ASADrug
Also called acetylsalicylic acid, Xarelto
rivaroxaban 2.5 mg orally BID and ASA 75-100 mg OD for 90 days
Low-molecular weight heparinDrug
Also called enoxaparin, dalteparin, tinzaparin
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
FondaparinuxDrug
Also called arixtra
2.5 mg subcutaneously OD
Direct Oral Anticoagulant (DOAC)Drug
Also called rivaroxaban, apixaban
Rivaroxaban 10 mg OD or apixaban 2.5 mg BID, started after surgery or after a period of LMWH.
| Study group | Role | What they receive |
|---|---|---|
| rivaroxaban plus ASA | Active comparator | rivaroxaban 2.5mg twice daily plus ASA 75-100mg daily for 90 days Receives: Drug: rivaroxaban and ASA |
| standard VTE prophylaxis with an anticoagulant | Active comparator | Institution's standard of care for thromboprophylaxis with a low-dose anticoagulant for ~30 days (as per the standard of care). Regimens could include low-molecular-weight heparin, fondaparinux, or direct oral anticoagulant. Receives: Drug: Low-molecular weight heparin; Drug: Fondaparinux; Drug: Direct Oral Anticoagulant (DOAC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment rate
Number of patients recruited per month per site
Measured: Through study completion, an average of 1 year.
Secondary outcomes (2)
FUP completion
Proportion of patients with a complete follow up
Measured: assessed at 30 and 90 days
Treatment adherence
Proportion of number of days on treatment
Measured: 30 and 90 days for the intervention, pre-specified treatment duration as per standard of care for the control.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2025
- Study start1 Dec 2025 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Hip Fracture SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network, International Network of VENous Thromboembolism Clinical Research Networks
- Responsible party
- Principal investigator, Federico Germini, McMaster University
- Investigators
- Federico Germini, Doctor of Medicine, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07228663
- Sponsor's protocol ID
- HIPSTER-2024
- Acronym
- HIPSTER-Pilot
- Status last verified
- Aug 2025
- First submitted
- 16 Aug 2025
- Last updated
- 14 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Available to share upon reasonable request, but will likely not unblind before completing a full-scale trial.
Publications
Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. doi: 10.1056/NEJMoa1712746.
PubMed 29466159Schulman S, Angeras U, Bergqvist D, Eriksson B, Lassen MR, Fisher W; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010 Jan;8(1):202-4. doi: 10.1111/j.1538-7836.2009.03678.x. Epub 2009 Oct 30.
PubMed 19878532Roshanov PS, Eikelboom JW, Sessler DI, Kearon C, Guyatt GH, Crowther M, Tandon V, Borges FK, Lamy A, Whitlock R, Biccard BM, Szczeklik W, Panju M, Spence J, Garg AX, McGillion M, VanHelder T, Kavsak PA, de Beer J, Winemaker M, Le Manach Y, Sheth T, Pinthus JH, Siegal D, Thabane L, Simunovic MRI, Mizera R, Ribas S, Devereaux PJ. Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study establishing diagnostic criteria and prognostic importance. Br J Anaesth. 2021 Jan;126(1):163-171. doi: 10.1016/j.bja.2020.06.051. Epub 2020 Aug 5.
PubMed 32768179Avery KN, Williamson PR, Gamble C, O'Connell Francischetto E, Metcalfe C, Davidson P, Williams H, Blazeby JM; members of the Internal Pilot Trials Workshop supported by the Hubs for Trials Methodology Research. Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies. BMJ Open. 2017 Feb 17;7(2):e013537. doi: 10.1136/bmjopen-2016-013537.
PubMed 28213598National Guideline Centre (UK). Venous thromboembolism in over 16s: Reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. London: National Institute for Health and Care Excellence (NICE); 2018 Mar. Available from http://www.ncbi.nlm.nih.gov/books/NBK493720/
PubMed 29697228Halvorsen S, Mehilli J, Cassese S, Hall TS, Abdelhamid M, Barbato E, De Hert S, de Laval I, Geisler T, Hinterbuchner L, Ibanez B, Lenarczyk R, Mansmann UR, McGreavy P, Mueller C, Muneretto C, Niessner A, Potpara TS, Ristic A, Sade LE, Schirmer H, Schupke S, Sillesen H, Skulstad H, Torracca L, Tutarel O, Van Der Meer P, Wojakowski W, Zacharowski K; ESC Scientific Document Group. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J. 2022 Oct 14;43(39):3826-3924. doi: 10.1093/eurheartj/ehac270. No abstract available.
PubMed 36017553Duceppe E, Parlow J, MacDonald P, Lyons K, McMullen M, Srinathan S, Graham M, Tandon V, Styles K, Bessissow A, Sessler DI, Bryson G, Devereaux PJ. Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery. Can J Cardiol. 2017 Jan;33(1):17-32. doi: 10.1016/j.cjca.2016.09.008. Epub 2016 Oct 4.
PubMed 27865641Devereaux PJ, Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, Borges FK, Martinez-Zapata MJ, Wang CY, Xavier D, Ofori SN, Wang MK, Efremov S, Landoni G, Kleinlugtenbelt YV, Szczeklik W, Schmartz D, Garg AX, Short TG, Wittmann M, Meyhoff CS, Amir M, Torres D, Patel A, Duceppe E, Ruetzler K, Parlow JL, Tandon V, Fleischmann E, Polanczyk CA, Lamy A, Astrakov SV, Rao M, Wu WKK, Bhatt K, de Nadal M, Likhvantsev VV, Paniagua P, Aguado HJ, Whitlock RP, McGillion MH, Prystajecky M, Vincent J, Eikelboom J, Copland I, Balasubramanian K, Turan A, Bangdiwala SI, Stillo D, Gross PL, Cafaro T, Alfonsi P, Roshanov PS, Belley-Cote EP, Spence J, Richards T, VanHelder T, McIntyre W, Guyatt G, Yusuf S, Leslie K; POISE-3 Investigators. Tranexamic Acid in Patients Undergoing Noncardiac Surgery. N Engl J Med. 2022 May 26;386(21):1986-1997. doi: 10.1056/NEJMoa2201171. Epub 2022 Apr 2.
PubMed 35363452Douketis JD, Spyropoulos AC, Murad MH, Arcelus JI, Dager WE, Dunn AS, Fargo RA, Levy JH, Samama CM, Shah SH, Sherwood MW, Tafur AJ, Tang LV, Moores LK. Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline. Chest. 2022 Nov;162(5):e207-e243. doi: 10.1016/j.chest.2022.07.025. Epub 2022 Aug 11.
PubMed 35964704Sheth T, Natarajan MK, Hsieh V, Valettas N, Rokoss M, Mehta S, Jolly S, Tandon V, Bezerra H, Devereaux PJ. Incidence of thrombosis in perioperative and non-operative myocardial infarction. Br J Anaesth. 2018 Apr;120(4):725-733. doi: 10.1016/j.bja.2017.11.063. Epub 2017 Nov 21.
PubMed 29576113Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, Patel MR, Fanelli F, Capell WH, Diao L, Jaeger N, Hess CN, Pap AF, Kittelson JM, Gudz I, Matyas L, Krievins DK, Diaz R, Brodmann M, Muehlhofer E, Haskell LP, Berkowitz SD, Hiatt WR. Rivaroxaban in Peripheral Artery Disease after Revascularization. N Engl J Med. 2020 May 21;382(21):1994-2004. doi: 10.1056/NEJMoa2000052. Epub 2020 Mar 28.
PubMed 32222135Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
PubMed 15842354Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O'Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, Stork S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S; COMPASS Investigators. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017 Oct 5;377(14):1319-1330. doi: 10.1056/NEJMoa1709118. Epub 2017 Aug 27.
PubMed 28844192Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S, Yusuf S; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1494-503. doi: 10.1056/NEJMoa1401105. Epub 2014 Mar 31.
PubMed 24679062Devereaux PJ, Duceppe E, Guyatt G, Tandon V, Rodseth R, Biccard BM, Xavier D, Szczeklik W, Meyhoff CS, Vincent J, Franzosi MG, Srinathan SK, Erb J, Magloire P, Neary J, Rao M, Rahate PV, Chaudhry NK, Mayosi B, de Nadal M, Iglesias PP, Berwanger O, Villar JC, Botto F, Eikelboom JW, Sessler DI, Kearon C, Pettit S, Sharma M, Connolly SJ, Bangdiwala SI, Rao-Melacini P, Hoeft A, Yusuf S; MANAGE Investigators. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet. 2018 Jun 9;391(10137):2325-2334. doi: 10.1016/S0140-6736(18)30832-8.
PubMed 29900874