inDividual, Targeted thrombosIS Prophylaxis Versus the Standard 'One Size Fits All' Approach in Patients Undergoing Total hIp or Total kNee replaCemenT

NCT06581965 | Recruiting Phase 4 DMC

• 3 other identifiers: P24.0312023-510186-98-00U1111-1305-2311
• Study Type: interventional
• Target: 10,078
• Locations: 1 country
• Sites: 10

Brief Summary

After hip or knee replacement all patients receive a standardized treatment with blood thinners, this medication is called thrombosis prophylaxis. However, despite this standard treatment some individuals still develop venous thrombosis (VTE), while others experience bleeding. This indicates that not all patients have the same VTE risk following surgery. Individualizing the amount of thrombosis prophylaxis following surgery might lead to less thrombotic and bleeding events. In this study the investigators individualize the treatment with thrombosis prophylaxis based on the medical history of a patient. The main questions this study aims to answer are: Can thrombosis prophylaxis be shortened in patients with a low VTE risk to decrease the risk of bleeding without increasing the risk of VTE? Does an increase in the dose and duration of thrombosis prophylaxis in patients with a high VTE risk reduce the risk of VTE without inducing an unacceptable risk of bleeds? Researchers will compare both the shortened treatment in low VTE risk patients and the intensified and extended treatment in high VTE risk patients with the standard treatment to assess the risk of VTE and bleeding in comparison to the standard treatment. Participants will receive 4 questionnaires to evaluate whether they have experienced a VTE or bleed. For this study no additional hospital visits are necessary.

Conditions

Venous Thromboembolism; Venous Thromboses; Pulmonary Embolism; Deep Vein Thrombosis

Keywords

Venous thromboembolism; Prophylaxis; Individualized Medicine; Total hip arthroplasty; Total knee arthroplasty; Randomized controlled trial

Outcome Measures

Primary Outcomes (2)

• Venous thromboembolic events

  Number of VTEs in the first 3 months postoperative.

  90 days postoperative

• Major bleeding

  Number of major bleeds in the first 3 months postoperative.

  90 days postoperative

Secondary Outcomes (10)

• Clinically relevant non major bleeding

  90 days postoperative

• Impact of events on QALY's

  90 days and 1 year postoperative

• Healthcare costs

  90 days and 1 year postoperative

• Prosthetic joint infections

  90 days postoperative

• Patient reported quality of life

  90 days and 1 year postoperative

Study Arms (5)

DISTINCT 1 short duration prophylaxis

EXPERIMENTAL

Patients with a low VTE risk (predicted 3-months postoperative VTE risk \<1%) based on the TRiP(plasty) score. (Nemeth, 2024)

Other: Short duration prophylaxis

DISTINCT 1 control

ACTIVE COMPARATOR

Patients with a low VTE risk (predicted 3-months postoperative VTE risk \<1%) based on the TRiP(plasty) score. (Nemeth, 2024)

Other: Control

DISTINCT 2 observational arm

OTHER

Patients with an intermediate VTE risk (predicted 3-months postoperative VTE risk ≥1%-≤1.5%) based on the TRiP(plasty) score. (Nemeth, 2024)

Other: Control

DISTINCT 3 extended prophylaxis

EXPERIMENTAL

Patients with a high VTE risk (predicted 3-months postoperative VTE risk \>1.5%) based on the TRiP(plasty) score. (Nemeth, 2024)

Other: Higher intensity and longer duration prophylaxis

DISTINCT 3 control

ACTIVE COMPARATOR

Patients with a high VTE risk (predicted 3-months postoperative VTE risk \>1.5%) based on the TRiP(plasty) score. (Nemeth, 2024)

Other: Control

Interventions

Short duration prophylaxis OTHER

Only during hospitalization: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guideline "Antitrombotisch beleid". First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use (same type as used for control group).

DISTINCT 1 short duration prophylaxis

Higher intensity and longer duration prophylaxis OTHER

The use of any thrombocyte aggregation inhibitors should be discontinued 5 days prior to surgery. Day 0-2: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guidelines. First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use. Day 3: Apixaban 5mg b.i.d., continued until 6 weeks after surgery, conditional on the fact that no active bleeding of the surgical wound can be observed. In case of active bleeding, the prophylactic dose of thrombosis prophylaxis is continued. Thereafter, in case no active bleeding has been observed for 24 hours, the 5mg b.i.d. apixaban treatment will be started. The 5mg b.i.d. apixaban dose will be adjusted to 2.5mg b.i.d. in case of an impaired kidney function (defined as eGFR 10-30ml/min).

DISTINCT 3 extended prophylaxis

Control OTHER

4 weeks: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guidelines. First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use.

Also known as: Standard treatment

DISTINCT 1 control; DISTINCT 2 observational arm; DISTINCT 3 control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled to undergo an elective total hip arthroplasty or total knee arthroplasty
• Aged 18 years or older

You may not qualify if:

• Primary arthroplasty for fractures
• Revision surgery
• Hemiarthroplasty
• Pregnancy
• Current use of therapeutic anticoagulant therapy of any type (e.g., LMWH, DOAC, vitamin K antagonist)
• A contraindication for either study drug
• Insufficient knowledge of the Dutch language
• Insufficient mental or physical ability to fulfil trial requirements
• Active malignancy (i.e. cancer diagnosis within six months before surgery (excluding basal-cell or squamous-cell carcinoma of the skin), recently recurrent or progressive cancer or any cancer that required anti-cancer treatment within six months before surgery)
• Patients using thrombocyte aggregation inhibitors that cannot be temporarily discontinued at the discretion of their treating physician

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (10)

Gelre Ziekenhuizen

Apeldoorn, Gelderland, 7334 DZ, Netherlands

RECRUITING

Zuyderland

Geleen, Limburg, 6162 BG, Netherlands

RECRUITING

Anna Ziekenhuis

Geldrop, North Brabant, 5564EH, Netherlands

RECRUITING

Bravis ziekenhuis

Roosendaal, North Brabant, 4708 AE, Netherlands

NOT YET RECRUITING

Elisabeth-TweeSteden Ziekenhuis

Tilburg, North Brabant, 5022GC, Netherlands

RECRUITING

OLVG

Amsterdam, North Holland, 1091AC, Netherlands

RECRUITING

Bergman Clinics

Naarden, North Holland, 1411DE, Netherlands

RECRUITING

Isala ziekenhuis

Zwolle, Overijssel, 8025AB, Netherlands

RECRUITING

Alrijne

Leiderdorp, South Holland, 2353 GA, Netherlands

RECRUITING

Reinier Haga Orthopedisch Centrum

Zoetermeer, South Holland, 2725NA, Netherlands

RECRUITING

Related Publications (2)

• Nemeth B, Smeets M, Pedersen AB, Kristiansen EB, Nelissen R, Whyte M, Roberts L, de Lusignan S, le Cessie S, Cannegieter S, Arya R. Development and validation of a clinical prediction model for 90-day venous thromboembolism risk following total hip and total knee arthroplasty: a multinational study. J Thromb Haemost. 2024 Jan;22(1):238-248. doi: 10.1016/j.jtha.2023.09.033. Epub 2023 Nov 22.

  PMID: 38030547 BACKGROUND

• Kok RY, van Bodegom-Vos L, Ettema HB, Groenwold RHH, van den Hout WB, Huisman MV, Klok FA, Nelissen RGHH, van Rein N, van Veen M, Vehmeijer SBW, Wiegerinck JJI, Cannegieter SC, Nemeth B. Study protocol for the DISTINCT trial: inDividual, targeted thrombosIS prophylaxis versus the standard 'one-size-fits-all' approach in patients undergoing Total hIp or total kNee replaCemenT - a national, multicentre, randomised, multiarm, open-label trial. BMJ Open. 2025 Oct 6;15(10):e101180. doi: 10.1136/bmjopen-2025-101180.

  PMID: 41057196 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Study Officials

• Banne Nemeth, dr

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Banne Nemeth, dr

CONTACT

+31715264037; B.Nemeth@lumc.nl

Ruben Y Kok, drs

CONTACT

+31715265633; R.Y.Kok@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Blinded endpoint adjudication
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoctoral researcher Clinical epidemiology

Model Details: This trial consists of 3 study arms. DISTINCT 1 (low VTE risk \<1.0%): randomized (2 arms) DISTINCT 2 (intermediate VTE risk 1.0%-1.5%): observational DISTINCT 3 (high VTE risk \>1.5%): randomized (2 arms) Participants will be allocated to a study arm based on their predicted VTE risk which is determined by the TRiP(plasty) score.

Study Record Dates

• First Submitted: August 25, 2024
• First Posted: September 3, 2024
• Study Start: November 11, 2024
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): February 1, 2031
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

NL (10)