Hip Arthroplasty, TotalPhase 3ENABLE-HipNCT06611319
ENhanced Recovery and ABbreviated LEngth of Anticoagulation for Thromboprophylaxis After Primary Hip Arthroplasty
A Phase 3 study testing Prevention of Venous Thromboembolism in people with Hip Arthroplasty, Total and Prevention of Venous Thromboembolism, run by Prof. Stavros Konstantinides, MD at 6 sites in 2 countries.
Trial summary
Surgical hip replacement (total hip arthroplasty, THA) is associated with a high risk of venous thromboembolism, but the appropriate duration of postoperative medical thromboprophylaxis ("anticoagulation") remains highly controversial. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hip Arthroplasty, Total, Prevention of Venous Thromboembolism
- What is being tested?
- Prevention of Venous Thromboembolism
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,932 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 26 Nov 2024to Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Age between 18 and 85 years
- Scheduled to undergo elective unilateral primary THA and eligible for perioperative management based on the ERAS protocol
- Baseline Timed Up and Go (TUG) test scoring \< 20 seconds, corresponding to a good mobility status before surgery
- Capability to understand and comply with the protocol requirements (e.g., sufficient knowledge of German language to answer the questionnaires, ability to swallow intact capsules).
- Pregnancy and contraception:
- Pregnancy test: Negative serum pregnancy test at screening for women of childbearing potential (WOCBP).
- Contraception: WOCBP and men who are able to father a child, willing to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of drug treatment and allowing for a safe wash out period of at least 5 days for female or for male subjects after the last dose of trial medication. This is a very conservative estimate, considering the 'worst case scenario' of a substantially prolonged half-life up to 13 hours (e.g., in older patients and/or those with renal dysfunction) (28), and calculating for at least 8 half-lives to ensure practically non-detectable levels and effects of rivaroxaban.
Who cannot join
- Previous DVT or PE
- Hip or lower limb fracture in the previous three months
- Major surgical procedure within the previous three months
- Active cancer defined as metastatic cancer, or cancer requiring chemotherapy or radiation therapy
- Active peptic ulcer disease, gastritis, or prior gastrointestinal bleeding
- Obesity with body mass index (BMI) \> 40 kg/m2 body surface area
Show all 18Show fewer
- Severe renal impairment defined as estimated glomerular filtration rate \< 30ml/min
- Severe hepatic impairment defined as Child Pugh Class B or C
- Uncontrolled intercurrent illness (i.e., active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, interstitial lung disease, serious gastrointestinal conditions [e.g., diarrhea, malabsorption], psychiatric illness)
- Active or recent major bleeding at any site, or presence of any major risk factor for bleeding, which, in the judgment of the investigator, may significantly increase the bleeding risk during postoperative anticoagulation treatment
- Any other medical condition representing a contraindication to discharge within 6 days after surgery
- Expected requirement for major surgery within a 90-day period post THA
- Need for long-term anticoagulation (e.g., atrial fibrillation, previous VTE)
- Need for chronic antiplatelet therapy except for acetylsalicylic acid (ASA) at a dose ≤ 100 mg daily or clopidogrel 75 mg daily
- Previous participation in this trial
- Life expectancy \< 6 months
- Participation in another interventional clinical trial within the last 30 days prior to inclusion, unless during the observational follow-up period
- History of hypersensitivity to the investigational medicinal product (IMP) or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the IMP
Trial locations and contacts
6 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
6 sites in 2 countries
Germany5 sites, 5 recruiting
- Recruiting
Evangelical Forest Hospital Berlin - Orthopaedics and Trauma Surgery
Berlin, 13589
Ulrich Nöth, Professor, +49 30 3702-1002, Ulrich.Noeth@jsd.de
Ulrich Nöth, Professor
- Recruiting
University Medical Center Dresden, University Center for Orthopaedics, Trauma & Plastic Surgery
Dresden, Saxony, 01307
Cornelia Lützner, Dr. rer. medic., +49 (0)351 458-13747, cornelia.luetzner@ukdd.de
Anne Schützer, +49 351 458 18610, anne.schuetzer@ukdd.de
- Recruiting
Sana Clinics Sommerfeld, Dpt. for Surgical Orthopaedics
Kremmen, Brandenburg, 16766
Andreas Halder, Professor, +4933055 5-2201, Andreas.Halder@sana-hu.de
Andreas Halder, Professor
- Recruiting
University Medical Center Mainz, Center for Orthopedics and Trauma Surgery
Mainz, Rhineland-Palatine, 55131
Valentina Nichelmann, +496131177198, valtentina.nichelmann@unimedizin-mainz.de
Yama Afghanyar, MD, +49 6131 172845, yama.afghanyar@unimedizin-mainz.de
- Recruiting
GPR Rüsselsheim Health and Care Center
Rüsselsheim am Main, Hesse, 65428
Manfred Krieger, MD, +496142 95630, krieger@gpr-mvz.de
Stephanie Uhl, +496142-882333, uhl@gp-ruesselsheim.de
Austria1 site, 1 recruiting
- Recruiting
Kepler University Medical Center, Orthopedics and Traumatology
Linz, Upper Austria, 4020
Viktoria Sperrer, MSc, +43 5 7680 83 78618, viktoria.sperrer@kepleruniklinikum.at
Christian Stadler, MD, +43 5 7680 83 73303, christian.stadler@kepleruniklinikum.at
About this study
Surgical hip replacement (total hip arthroplasty, THA) is associated with a high risk of venous thromboembolism, but the appropriate duration of postoperative medical thromboprophylaxis ("anticoagulation") remains highly controversial. The international randomized controlled trial (RCT) "ENhanced recovery and ABbreviated LEngth of Anticoagulation for Thromboprophylaxis after primary Hip Arthroplasty" (ENABLE-Hip) will enroll patients undergoing elective THA that are eligible for early mobilization after surgery. The trial will compare a regimen of short-duration (10-day) postoperative anticoagulation (experimental group) to standard-duration (35-day) postoperative anticoagulation (control group) using the direct oral anticoagulant Rivaroxaban (brand name: Xarelto) at the recommended dose. Thus, ENABLE-Hip will be the first major RCT to directly test an overall reduction in the duration of post-THA thromboprophylaxis instead of replacing one antithrombotic drug or regimen by another. Follow-up visits after hospital discharge will be on day 35 and on day 90 after surgery. The primary outcome is acute symptomatic proximal deep vein thrombosis, or symptomatic or fatal pulmonary embolism, within 90 days after surgery. If ENABLE-Hip will demonstrate 'non-inferiority' of the experimental intervention, its benefits will be obvious, as patients are spared many days of unnecessary (and potentially harmful in terms of bleeding risk) anticoagulation.
Read the detailed description
An increasing proportion of the ageing population in Europe and other parts of the world suffers from hip osteoarthritis and will need surgical joint arthroplasty at some time in their lives. Surgical total hip arthroplasty (THA) is associated with a high risk of venous thromboembolism (VTE), but the appropriate duration of postoperative anticoagulation remains highly controversial. Although current German guidelines continue to advocate anticoagulation for 28-35 days after THA, clinical practice recommendations in other countries are shifting towards much earlier discontinuation of anticoagulants - despite the absence of solid evidence backed by controlled data. The "Enhanced recovery and Abbreviated duration of Anticoagulation for thromboprophylaxis after primary hip Arthroplasty" (ENABLE-Hip) study is a multicentre investigator-initiated and academically sponsored prospective randomised active-control non-inferiority trial. A regimen of short-duration (10-day) prophylactic anticoagulation (experimental arm) will be compared to standard-duration (35-day) anticoagulation as per current guidelines (control arm). Patients will be mobilised early after surgery, following a standardised enhanced recovery protocol. Following randomisation and an initial two-day open-label period of prophylactic anticoagulation as per local protocol, treatment with the study drug (rivaroxaban at the standard, approved prophylactic dose of 10 mg daily) will be started and continued until 10 days after surgery. After this time, patients will be switched (in a double-blinded manner) to placebo in the experimental arm, or continue on active drug in the control arm, until a total of 35 days have elapsed since surgery. The primary outcome is acute symptomatic proximal deep vein thrombosis (DVT), or symptomatic or fatal pulmonary embolism (PE), within the first 3 months after surgery. Participating investigators will be advised to adhere to guideline recommendations regarding clinical suspicion of and diagnostic work-up for VTE. The planned study population of 2,932 patients will provide ≥ 80% power to reject the null hypothesis that δ ≥ 0.01 (where δ = difference between the two arms in symptomatic VTE probability within 3 months) and accept the alternative hypothesis that δ < 0.01, at an overall significance level α = 0.05. A formal interim analysis will be performed after 3-month follow-up of the first 1,760 randomised patients at a significance level α = 0.50, leading to stopping for futility if significance is not obtained, or if recalculation yields an overall sample size of > 3,200 patients. The trial has the potential to inform future national and European guidelines for this large and continuously growing patient population.
- Being tested
- Prevention of Venous Thromboembolism, Placebo Oral Tablet
- Keywords
- Thromboprophylaxis after hip surgery, Rivaroxaban, Abbreviated length of Anticoagulation, Enhanced recovery after surgery, Fast-track surgery, Early mobilization, Pulmonary embolism, Deep vein thrombosis
- Medical subject headings
- Pulmonary Embolism, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prevention of Venous ThromboembolismDrug
Also called Rivaroxaban, Xarelto, anticoag, Direct oral anticoagulant
Direct oral anticoagulant
Placebo Oral TabletDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Abbreviated lenght of thromboprophylaxis | Experimental | Rivaroxaban from day 3-10; Placebo from day 11-35 after surgery Receives: Drug: Prevention of Venous Thromboembolism; Drug: Placebo Oral Tablet |
| Standard of care | Active comparator | Rivaroxaban from day 3-35 after surgery Receives: Drug: Prevention of Venous Thromboembolism |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy endpoint is the rate of acute symptomatic or fatal VTE
acute symptomatic or fatal VTE, defined as (i) symptomatic DVT of the popliteal or more proximal leg veins (femoral or iliac veins) or inferior vena cava; or (ii) symptomatic (segmental or more proximal) or fatal PE, occurring in the first 90 days after surgery and confirmed by objective testing.
Measured: within 90 days after surgery
Secondary outcomes (12)
Length of hospital stay
duration of inpatient stay
Measured: within 90 days after surgery
Changes in patient-reported hip joint-specific disability
assessment is made following surgery measured by the HOOS-12 score
Measured: within 90 days after surgery
Rate of clinically relevant non-major bleedings
it does not meet the criteria for major bleeding, but results in hospitalization, aspiration of a wound, or a wound hematoma complicated by infection.
Measured: within 90 days after surgery
Rate of death from any cause
rate of death from any cause
Measured: within 90 days after surgery
Rate of isolated symptomatic distal DVT
rate of symptomatic distal DVT
Measured: within 90 days after surgery
Rate of myocardial infarction (MI) or stroke
rate of MI or stroke
Measured: within 90 days after surgery
Rate of readmission to the hospital
rate of readmissions to the hospital
Measured: within 90 days after surgery
Number and terms of serious adverse events (SAEs)
number of SAEs during study duration
Measured: within 90 days after surgery
Change in patient mobility
measured by Range of motion (ROM) and Timed up and Go (TUG) score
Measured: within 90 days after surgery
Amount of postoperative healthcare resource utilization
visits to health care providers and rehospitalization, employment status
Measured: within 35 days after surgery
Rate of major bleedings
fulfils at least one of the following criteria: (i) fatal (ii) bleeding into a critical area or organ (iii) surgical site bleeding that causes hemodynamic instability (iv) non-surgical site bleeding causing a fall in hemoglobin level of ≥ 20 g L-1, or leading to transfusion of ≥ 2 units of whole blood or red blood cells (v) surgical site bleeding that requires a second intervention (open, arthroscopic, endovascular), or hemarthron of sufficient size to delay mobilization or wound healing
Measured: within 90 days after surgery
Generic quality of life measured by EQ-5D-5L
The EQ-5D is not an abbreviation and is the correct term to use in print or verbally.
EQ-5D-5L consists of 2 parts:
- descriptive system consists of 5 dimensions with 5 levels each. A score of 5 at a minimum means best health state; a score of 25 at a maximum means worst health state.
- EQ VAS: a scale from 0 (worst health state) to 100 (best health state) is provided.
This questionnaire is to be completed by the patient for the current day.
Measured: within 90 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2024
- Study start26 Nov 2024
- Primary completionMar 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for Hip Arthroplasty, TotalStudies 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
- Investigator-initiated and academically sponsored multicenter randomized double blind active-control non-inferiority trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,932 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Stavros Konstantinides, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Stavros Konstantinides, MD, Johannes Gutenberg University Mainz
- Investigators
- Stavros V. Konstantinides, MD, Univ.-Prof., Study chair, University Medical Center Mainz, Center for Thrombosis and HemostasisPhilipp Drees, MD, Univ.-Prof., Study chair, University Medical Center Mainz, Center for Orthopedics and Trauma Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06611319
- Sponsor's protocol ID
- 23-01496
- Other IDs
- 2023-507490-18-00, 2023
- Acronym
- ENABLE-Hip
- Status last verified
- Jan 2025
- First submitted
- 23 Sep 2024
- Last updated
- 16 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat Med. 2011 Dec 10;30(28):3267-84. doi: 10.1002/sim.4102. Epub 2010 Nov 30.
PubMed 22105690Mohr K, Mildenberger P, Neusius T, Christodoulou KC, Farmakis IT, Kaier K, Barco S, Klok FA, Hobohm L, Keller K, Becker D, Abele C, Bruch L, Ewert R, Schmidtmann I, Wild PS, Rosenkranz S, Konstantinides SV, Binder H, Valerio L; FOCUS Investigators. Estimated annual healthcare costs after acute pulmonary embolism: results from a prospective multicentre cohort study. Eur Heart J Qual Care Clin Outcomes. 2025 May 1;11(3):334-342. doi: 10.1093/ehjqcco/qcae050.
PubMed 38950900Klein JP, Logan B, Harhoff M, Andersen PK. Analyzing survival curves at a fixed point in time. Stat Med. 2007 Oct 30;26(24):4505-19. doi: 10.1002/sim.2864.
PubMed 17348080Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.
PubMed 21830957Hood BR, Cowen ME, Zheng HT, Hughes RE, Singal B, Hallstrom BR. Association of Aspirin With Prevention of Venous Thromboembolism in Patients After Total Knee Arthroplasty Compared With Other Anticoagulants: A Noninferiority Analysis. JAMA Surg. 2019 Jan 1;154(1):65-72. doi: 10.1001/jamasurg.2018.3858.
PubMed 30347089Farmakis IT, Kaier K, Hobohm L, Mohr K, Valerio L, Barco S, Konstantinides SV, Binder H. Healthcare resource utilisation and associated costs after low-risk pulmonary embolism: pre-specified analysis of the Home Treatment of Pulmonary Embolism (HoT-PE) study. Clin Res Cardiol. 2025 Feb;114(2):168-176. doi: 10.1007/s00392-023-02355-5. Epub 2024 Jan 3.
PubMed 38170252Schoene D, Wu SM, Mikolaizak AS, Menant JC, Smith ST, Delbaere K, Lord SR. Discriminative ability and predictive validity of the timed up and go test in identifying older people who fall: systematic review and meta-analysis. J Am Geriatr Soc. 2013 Feb;61(2):202-8. doi: 10.1111/jgs.12106. Epub 2013 Jan 25.
PubMed 23350947Prather H, Harris-Hayes M, Hunt DM, Steger-May K, Mathew V, Clohisy JC. Reliability and agreement of hip range of motion and provocative physical examination tests in asymptomatic volunteers. PM R. 2010 Oct;2(10):888-95. doi: 10.1016/j.pmrj.2010.05.005.
PubMed 20970757Gandek B, Roos EM, Franklin PD, Ware JE Jr. A 12-item short form of the Hip disability and Osteoarthritis Outcome Score (HOOS-12): tests of reliability, validity and responsiveness. Osteoarthritis Cartilage. 2019 May;27(5):754-761. doi: 10.1016/j.joca.2018.09.017. Epub 2018 Nov 10.
PubMed 30419279Nilsdotter AK, Lohmander LS, Klassbo M, Roos EM. Hip disability and osteoarthritis outcome score (HOOS)--validity and responsiveness in total hip replacement. BMC Musculoskelet Disord. 2003 May 30;4:10. doi: 10.1186/1471-2474-4-10. Epub 2003 May 30.
PubMed 12777182Blasimann A, Dauphinee SW, Staal JB. Translation, cross-cultural adaptation, and psychometric properties of the German version of the hip disability and osteoarthritis outcome score. J Orthop Sports Phys Ther. 2014 Dec;44(12):989-97. doi: 10.2519/jospt.2014.4994. Epub 2014 Nov 13.
PubMed 25394689Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9.
PubMed 21479777Halvorsen 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 36017553Steffel J, Collins R, Antz M, Cornu P, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Vanassche T, Potpara T, Camm AJ, Heidbuchel H; External reviewers. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021 Oct 9;23(10):1612-1676. doi: 10.1093/europace/euab065. No abstract available.
PubMed 33895845Kutzner KP, Meyer A, Bausch M, Schneider M, Rehbein P, Drees P, Pfeil J. Outcome of an "Enhanced Recovery" Program in Contemporary Total Hip Arthroplasty in Germany. Z Orthop Unfall. 2020 Apr;158(2):214-220. doi: 10.1055/a-0946-2523. Epub 2019 Sep 16. English, German.
PubMed 31525792
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ENhanced Recovery and ABbreviated LEngth of Anticoagulation for Thromboprophylaxis After Primary Hip Arthroplasty
- ClinicalTrials.gov ID
- NCT06611319
- Acronym / sponsor ID
- ENABLE-Hip / 23-01496
- Keywords
- Thromboprophylaxis after hip surgery, Rivaroxaban, Abbreviated length of Anticoagulation, Enhanced recovery after surgery, Fast-track surgery, Early mobilization, Pulmonary embolism, Deep vein thrombosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,932 participants (estimated)
- Lead sponsor
- Prof. Stavros Konstantinides, MDUniversity, hospital or other
- Study start
- 26 Nov 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 24 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Surgical hip replacement (total hip arthroplasty, THA) is associated with a high risk of venous thromboembolism, but the appropriate duration of postoperative medical thromboprophylaxis ("anticoagulation") remains highly controversial. The international randomized controlled trial (RCT) "ENhanced recovery and ABbreviated LEngth of Anticoagulation for Thromboprophylaxis after primary Hip Arthroplasty" (ENABLE-Hip) will enroll patients undergoing elective THA that are eligible for early mobilization after surgery. The trial will compare a regimen of short-duration (10-day) postoperative anticoagulation (experimental group) to standard-duration (35-day) postoperative anticoagulation (control group) using the direct oral anticoagulant Rivaroxaban (brand name: Xarelto) at the recommended dose. Thus, ENABLE-Hip will be the first major RCT to directly test an overall reduction in the duration of post-THA thromboprophylaxis instead of replacing one antithrombotic drug or regimen by another. Follow-up visits after hospital discharge will be on day 35 and on day 90 after surgery. The primary outcome is acute symptomatic proximal deep vein thrombosis, or symptomatic or fatal pulmonary embolism, within 90 days after surgery. If ENABLE-Hip will demonstrate 'non-inferiority' of the experimental intervention, its benefits will be obvious, as patients are spared many days of unnecessary (and potentially harmful in terms of bleeding risk) anticoagulation.
Detailed description
An increasing proportion of the ageing population in Europe and other parts of the world suffers from hip osteoarthritis and will need surgical joint arthroplasty at some time in their lives. Surgical total hip arthroplasty (THA) is associated with a high risk of venous thromboembolism (VTE), but the appropriate duration of postoperative anticoagulation remains highly controversial. Although current German guidelines continue to advocate anticoagulation for 28-35 days after THA, clinical practice recommendations in other countries are shifting towards much earlier discontinuation of anticoagulants - despite the absence of solid evidence backed by controlled data. The "Enhanced recovery and Abbreviated duration of Anticoagulation for thromboprophylaxis after primary hip Arthroplasty" (ENABLE-Hip) study is a multicentre investigator-initiated and academically sponsored prospective randomised active-control non-inferiority trial. A regimen of short-duration (10-day) prophylactic anticoagulation (experimental arm) will be compared to standard-duration (35-day) anticoagulation as per current guidelines (control arm). Patients will be mobilised early after surgery, following a standardised enhanced recovery protocol. Following randomisation and an initial two-day open-label period of prophylactic anticoagulation as per local protocol, treatment with the study drug (rivaroxaban at the standard, approved prophylactic dose of 10 mg daily) will be started and continued until 10 days after surgery. After this time, patients will be switched (in a double-blinded manner) to placebo in the experimental arm, or continue on active drug in the control arm, until a total of 35 days have elapsed since surgery. The primary outcome is acute symptomatic proximal deep vein thrombosis (DVT), or symptomatic or fatal pulmonary embolism (PE), within the first 3 months after surgery. Participating investigators will be advised to adhere to guideline recommendations regarding clinical suspicion of and diagnostic work-up for VTE. The planned study population of 2,932 patients will provide ≥ 80% power to reject the null hypothesis that δ ≥ 0.01 (where δ = difference between the two arms in symptomatic VTE probability within 3 months) and accept the alternative hypothesis that δ < 0.01, at an overall significance level α = 0.05. A formal interim analysis will be performed after 3-month follow-up of the first 1,760 randomised patients at a significance level α = 0.50, leading to stopping for futility if significance is not obtained, or if recalculation yields an overall sample size of > 3,200 patients. The trial has the potential to inform future national and European guidelines for this large and continuously growing patient population.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Investigator-initiated and academically sponsored multicenter randomized double blind active-control non-inferiority trial
| Arm | Type | Receives |
|---|---|---|
| Abbreviated lenght of thromboprophylaxis | Experimental | Drug: Prevention of Venous Thromboembolism, Drug: Placebo Oral TabletRivaroxaban from day 3-10; Placebo from day 11-35 after surgery |
| Standard of care | Active comparator | Drug: Prevention of Venous ThromboembolismRivaroxaban from day 3-35 after surgery |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent
- Age between 18 and 85 years
- Scheduled to undergo elective unilateral primary THA and eligible for perioperative management based on the ERAS protocol
- Baseline Timed Up and Go (TUG) test scoring \&lt; 20 seconds, corresponding to a good mobility status before surgery
- Capability to understand and comply with the protocol requirements (e.g., sufficient knowledge of German language to answer the questionnaires, ability to swallow intact capsules).
Key exclusion criteria (18 listed)
- Previous DVT or PE
- Hip or lower limb fracture in the previous three months
- Major surgical procedure within the previous three months
- Active cancer defined as metastatic cancer, or cancer requiring chemotherapy or radiation therapy
- Active peptic ulcer disease, gastritis, or prior gastrointestinal bleeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prevention of Venous ThromboembolismAlso: Rivaroxaban, Xarelto, anticoag, Direct oral anticoagulantDirect oral anticoagulant | Drug | Abbreviated lenght of thromboprophylaxis, Standard of care |
| Placebo Oral TabletPlacebo | Drug | Abbreviated lenght of thromboprophylaxis |
Primary outcome
The primary efficacy endpoint is the rate of acute symptomatic or fatal VTE
Time frame: within 90 days after surgery
acute symptomatic or fatal VTE, defined as (i) symptomatic DVT of the popliteal or more proximal leg veins (femoral or iliac veins) or inferior vena cava; or (ii) symptomatic (segmental or more proximal) or fatal PE, occurring in the first 90 days after surgery and confirmed by objective testing.
12 secondary outcomes
Length of hospital stay
Time frame: within 90 days after surgery
Changes in patient-reported hip joint-specific disability
Time frame: within 90 days after surgery
Rate of clinically relevant non-major bleedings
Time frame: within 90 days after surgery
Rate of death from any cause
Time frame: within 90 days after surgery
Rate of isolated symptomatic distal DVT
Time frame: within 90 days after surgery
Rate of myocardial infarction (MI) or stroke
Time frame: within 90 days after surgery
Rate of readmission to the hospital
Time frame: within 90 days after surgery
Number and terms of serious adverse events (SAEs)
Time frame: within 90 days after surgery
Change in patient mobility
Time frame: within 90 days after surgery
Amount of postoperative healthcare resource utilization
Time frame: within 35 days after surgery
Rate of major bleedings
Time frame: within 90 days after surgery
Generic quality of life measured by EQ-5D-5L
Time frame: within 90 days after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2025.
- Background: PubMed 22105690Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat Med. 2011 Dec 10;30(28):3267-84. doi: 10.1002/sim.4102. Epub 2010 Nov 30.
- Background: PubMed 38950900Mohr K, Mildenberger P, Neusius T, Christodoulou KC, Farmakis IT, Kaier K, Barco S, Klok FA, Hobohm L, Keller K, Becker D, Abele C, Bruch L, Ewert R, Schmidtmann I, Wild PS, Rosenkranz S, Konstantinides SV, Binder H, Valerio L; FOCUS Investigators. Estimated annual healthcare costs after acute pulmonary embolism: results from a prospective multicentre cohort study. Eur Heart J Qual Care Clin Outcomes. 2025 May 1;11(3):334-342. doi: 10.1093/ehjqcco/qcae050.
- Background: PubMed 17348080Klein JP, Logan B, Harhoff M, Andersen PK. Analyzing survival curves at a fixed point in time. Stat Med. 2007 Oct 30;26(24):4505-19. doi: 10.1002/sim.2864.
- Background: PubMed 21830957Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.
- Background: PubMed 30347089Hood BR, Cowen ME, Zheng HT, Hughes RE, Singal B, Hallstrom BR. Association of Aspirin With Prevention of Venous Thromboembolism in Patients After Total Knee Arthroplasty Compared With Other Anticoagulants: A Noninferiority Analysis. JAMA Surg. 2019 Jan 1;154(1):65-72. doi: 10.1001/jamasurg.2018.3858.
- Background: PubMed 38170252Farmakis IT, Kaier K, Hobohm L, Mohr K, Valerio L, Barco S, Konstantinides SV, Binder H. Healthcare resource utilisation and associated costs after low-risk pulmonary embolism: pre-specified analysis of the Home Treatment of Pulmonary Embolism (HoT-PE) study. Clin Res Cardiol. 2025 Feb;114(2):168-176. doi: 10.1007/s00392-023-02355-5. Epub 2024 Jan 3.
- Background: PubMed 23350947Schoene D, Wu SM, Mikolaizak AS, Menant JC, Smith ST, Delbaere K, Lord SR. Discriminative ability and predictive validity of the timed up and go test in identifying older people who fall: systematic review and meta-analysis. J Am Geriatr Soc. 2013 Feb;61(2):202-8. doi: 10.1111/jgs.12106. Epub 2013 Jan 25.
- Background: PubMed 20970757Prather H, Harris-Hayes M, Hunt DM, Steger-May K, Mathew V, Clohisy JC. Reliability and agreement of hip range of motion and provocative physical examination tests in asymptomatic volunteers. PM R. 2010 Oct;2(10):888-95. doi: 10.1016/j.pmrj.2010.05.005.
- Background: PubMed 30419279Gandek B, Roos EM, Franklin PD, Ware JE Jr. A 12-item short form of the Hip disability and Osteoarthritis Outcome Score (HOOS-12): tests of reliability, validity and responsiveness. Osteoarthritis Cartilage. 2019 May;27(5):754-761. doi: 10.1016/j.joca.2018.09.017. Epub 2018 Nov 10.
- Background: PubMed 12777182Nilsdotter AK, Lohmander LS, Klassbo M, Roos EM. Hip disability and osteoarthritis outcome score (HOOS)--validity and responsiveness in total hip replacement. BMC Musculoskelet Disord. 2003 May 30;4:10. doi: 10.1186/1471-2474-4-10. Epub 2003 May 30.
- Background: PubMed 25394689Blasimann A, Dauphinee SW, Staal JB. Translation, cross-cultural adaptation, and psychometric properties of the German version of the hip disability and osteoarthritis outcome score. J Orthop Sports Phys Ther. 2014 Dec;44(12):989-97. doi: 10.2519/jospt.2014.4994. Epub 2014 Nov 13.
- Background: PubMed 21479777Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Stavros V. Konstantinides, MD, Univ.-Prof. study chair
University Medical Center Mainz, Center for Thrombosis and Hemostasis
Philipp Drees, MD, Univ.-Prof. study chair
University Medical Center Mainz, Center for Orthopedics and Trauma Surgery
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Prevention of Venous Thromboembolism in people with Hip Arthroplasty, Total and Prevention of Venous Thromboembolism, run by Prof. Stavros Konstantinides, MD at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nadine Martin, Dr. (+496131178376, nadine.martin@unimedizin-mainz.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary efficacy endpoint is the rate of acute symptomatic or fatal VTE (time frame: within 90 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06611319, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2025.