Enhanced recovery and abbreviated length of anticoagulation for thromboprophylaxis after primary hip arthroplasty rationale and design of the ENABLE-hip trial

Philipp Drees¹, Irene Schmidtmann², Manuel Herbst², Dorothea Becker³, Stefano Barco^{3

4}, Frederikus A Klok^{3

5}, Karsten Keller^{3

6}, Lukas Hobohm^{3

6}, Konstantinos C Christodoulou³, Christina Abele³, Rupert Bauersachs⁷, Walter Ageno⁸, Erik Lerkevang Grove^{9

10}, Henrik Kehlet¹¹, Friedhelm Hufen¹², Thomas Klonschinski¹, Yama Afghanyar¹, Lukas Eckhard¹³, Nadine Martin³, Susanne Fischer³, Stanislav Gorbulev¹⁴, Dominik Rath¹⁵, Anna C Mavromanoli^{3

16}, Claude Jabbour¹⁷, Irene Lang¹⁸, Francis Couturaud^{19

20

21}, Christian Heiss²², Harald Binder²³, Stavros Konstantinides²⁴

Affiliations

¹ Center for Orthopedics and Trauma Surgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
² Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁴ Department of Angiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Medicine-Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
⁶ Department of Cardiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁷ Cardioangiologic Center Bethanien CCB, Frankfurt Am Main, Germany.
⁸ Department of Internal Medicine, University of Padua, Padua, Italy.
⁹ Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
¹⁰ Department of Clinical Medicine, Faculty of Healthy, Aarhus University, Aarhus, Denmark.
¹¹ Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark.
¹² , Mainz, Germany.
¹³ Joint Surgery Center, Bad Kreuznach, Germany.
¹⁴ Interdisciplinary Center for Clinical Trials, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹⁵ Department of Cardiology and Angiology, University Hospital Tübingen, Tübingen, Germany.
¹⁶ University Hospital Zurich, Zurich, Switzerland.
¹⁷ Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany.
¹⁸ Department of Internal Medicine II, Medical University of Vienna, Cardiology, Austria.
¹⁹ Univ_Brest, INSERM U1304-GERBI, CIC INSERM, 1412, Brest, France.
²⁰ Département de Médecine Interne Et Pneumologie, CHU Brest, Brest, France.
²¹ FCRIN INNOVTE Network, Saint-Etienne, France.
²² Trauma, Hand and Reconstructive Surgery, Justus Liebig University, Giessen, Germany.
²³ Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
²⁴ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. stavros.konstantinides@unimedizin-mainz.de.

PMID: 40442449
PMCID: PMC12350570
DOI: 10.1007/s11239-025-03110-5

Enhanced recovery and abbreviated length of anticoagulation for thromboprophylaxis after primary hip arthroplasty rationale and design of the ENABLE-hip trial

Philipp Drees et al. J Thromb Thrombolysis. 2025 Aug.

. 2025 Aug;58(6):689-698.

doi: 10.1007/s11239-025-03110-5. Epub 2025 May 29.

Authors

Affiliations

¹ Center for Orthopedics and Trauma Surgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
² Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁴ Department of Angiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Medicine-Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
⁶ Department of Cardiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁷ Cardioangiologic Center Bethanien CCB, Frankfurt Am Main, Germany.
⁸ Department of Internal Medicine, University of Padua, Padua, Italy.
⁹ Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
¹⁰ Department of Clinical Medicine, Faculty of Healthy, Aarhus University, Aarhus, Denmark.
¹¹ Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark.
¹² , Mainz, Germany.
¹³ Joint Surgery Center, Bad Kreuznach, Germany.
¹⁴ Interdisciplinary Center for Clinical Trials, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹⁵ Department of Cardiology and Angiology, University Hospital Tübingen, Tübingen, Germany.
¹⁶ University Hospital Zurich, Zurich, Switzerland.
¹⁷ Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany.
¹⁸ Department of Internal Medicine II, Medical University of Vienna, Cardiology, Austria.
¹⁹ Univ_Brest, INSERM U1304-GERBI, CIC INSERM, 1412, Brest, France.
²⁰ Département de Médecine Interne Et Pneumologie, CHU Brest, Brest, France.
²¹ FCRIN INNOVTE Network, Saint-Etienne, France.
²² Trauma, Hand and Reconstructive Surgery, Justus Liebig University, Giessen, Germany.
²³ Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
²⁴ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. stavros.konstantinides@unimedizin-mainz.de.

PMID: 40442449
PMCID: PMC12350570
DOI: 10.1007/s11239-025-03110-5

Abstract

Surgical total hip arthroplasty (THA) is associated with high risk of venous thromboembolism (VTE), but the appropriate duration of postoperative anticoagulation remains controversial. "Enhanced Recovery and Abbreviated Length of Anticoagulation for Thromboprophylaxis After Primary Hip Arthroplasty" (ENABLE-Hip) is a multicenter investigator-initiated and academically sponsored randomized double-blind active-control non-inferiority trial. Patients will be mobilized early after surgery, following a standardized enhanced recovery protocol. After an initial open-label prophylactic anticoagulation as per local standard of care until day 2 after surgery, treatment with rivaroxaban (10 mg once daily) will be started on day 3 and continued until day 10. Subsequently, patients will be switched to placebo in the experimental arm, or continue on active drug in the control arm, until a total of 35 days. The primary endpoint is acute symptomatic or fatal VTE within 3 months. A sample size of 2,932 patients will provide ≥ 80% power to reject the null hypothesis that δ ≥ 0.01 (δ = difference between the two arms in symptomatic VTE probability) at a significance level α = 0.05. An interim analysis will be performed after 3-month follow-up of the first 1,760 randomized patients at a significance level α = 0.50, leading to stop for futility if significance is not obtained, or if recalculation yields a sample size of > 3,200 patients. ENABLE-Hip will be the first major randomized trial to test an overall reduction in the duration of post-THA thromboprophylaxis and will inform future guideline recommendations concerning this continuously growing patient population.Trial registration: ClinicalTrials.gov Identifier: NCT06611319.

Keywords: Anticoagulation; Randomized controlled trial; Thromboprophylaxis; Total hip arthroplasty; Venous thromboembolism.

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Conflict of interest statement

Declarations. Conflict of interest: FAK received research funding from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, The Dutch Heart Foundation, and the Horizon Europe Program, all outside this work and paid to his institution. LH reports lecture/consultancy fees from Boston Scientific, INARI Medical, MSD and Johnson & Johnson, outside the submitted work. WA has participated in advisory boards for Astra Zeneca, Bayer, BMS-Pfizer, Leo Pharma, Norgine, Sanofi and Viatris. ELG has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Organon, Lundbeck Pharma and Novo Nordisk. He is investigator in studies sponsored by AstraZeneca, Idorsia and Bayer, and has received unrestricted research grants from Boehringer Ingelheim. IML has relationships with drug companies including AOP-Health, Actelion-Janssen, MSD, United Therapeutics, Pulnovo, Medtronic, NovoNordisk and Daiichi. In addition to being investigator in trials involving these companies, relationships include consultancy service, research grants, and membership of scientific advisory boards. FC reports having received research grant support from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme, GlaxoSmithKline, Chiesi and Astra Zeneca and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme, Leo Pharma, Sanofi and Chiesi. RB reports research support by the Bavarian State Ministry of Health, FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti), VIATRIS and personal fees from Bayer, Bristol Myers Squibb, LEO Pharma, Pfizer, VIATRIS outside the submitted work. SVK reports research grants or contracts to his institution from Bayer AG, Daiichi Sankyo, Boston Scientific Corp., Penumbra Inc., and Inari Medical; and personal consulting fees from Daiichi Sankyo, Boston Scientific Corp., Penumbra Inc. and Inari Medical, all outside the submitted work. All other authors declare no conflicts of interest.

References

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Enhanced recovery and abbreviated length of anticoagulation for thromboprophylaxis after primary hip arthroplasty rationale and design of the ENABLE-hip trial

Affiliations

Enhanced recovery and abbreviated length of anticoagulation for thromboprophylaxis after primary hip arthroplasty rationale and design of the ENABLE-hip trial

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical