Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
10,078
Countries
1
Sites
15
Venous thromboembolism
DISTINCT 1: to determine whether in-hospital thrombosis prophylaxis only is as effective compared with the standard thrombosis prophylaxis approach to prevent symptomatic VTE after total knee and hip arthroplasty in patients with a low VTE risk. DISTINCT 2: to determine the incidence of symptomatic VTE after total knee…
Key facts
- Sponsor
- Academisch Ziekenhuis Leiden
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 23 Oct 2024 → ongoing
- Decision date (initial)
- 2024-08-12
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- ZonMw
External identifiers
- EU CT number
- 2023-510186-98-00
- WHO UTN
- U1111-1305-2311
- ClinicalTrials.gov
- NCT06581965
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Prophylaxis
DISTINCT 1: to determine whether in-hospital thrombosis prophylaxis only is as effective compared with the standard thrombosis prophylaxis approach to prevent symptomatic VTE after total knee and hip arthroplasty in patients with a low VTE risk.
DISTINCT 2: to determine the incidence of symptomatic VTE after total knee and hip arthroplasty in patients with an intermediate VTE risk.
DISTINCT 3: to determine whether intensified thrombosis prophylaxis is more effective and equally safe compared with standard thrombosis prophylaxis to prevent symptomatic VTE in patients with a high VTE risk by comparing symptomatic VTE and bleeding complications.
Secondary objectives 6
- To compare risks of clinically relevant non-major bleeds between the targeted thrombosis prophylaxis approach and the standard approach.
- To compare the cost-effectiveness of the targeted thrombosis prophylaxis approach with the standard approach.
- To determine the incidence of prosthetic joint infection, overall and in subgroups.
- To compare patient reported outcome measures in the targeted thrombosis prophylaxis approach with the standard approach.
- To investigate the effect of VTE, bleeding and prosthetic joint infections on the functional outcomes after THA and TKA.
- To determine the incidence of myocardial infarction, stroke and death overall and in subgroups.
Conditions and MedDRA coding
Venous thromboembolism
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Subjects scheduled to undergo an elective Total Hip Arthroplasty or Total Knee Arthroplasty
- Subjects aged 18 years or older
Exclusion criteria 10
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Number of VTEs in the first 3 months postoperative
- Number of major bleeds in the first 3 months postoperative.
Secondary endpoints 8
- Clinically relevant non major bleeding
- Impact of events on QALY’s
- Healthcare costs
- Prosthetic joint infections
- Patient reported outcome measures
- Myocardial infarction
- Ischemic stroke
- Death
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SUB25425 · Substance
- Active substance
- Apixaban
- Pharmaceutical form
- FILM COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 40 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25425 · Substance
- Active substance
- Apixaban
- Pharmaceutical form
- FILM COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 40 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 9
SUB03372MIG · Substance
- Active substance
- Nadroparin Calcium
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 2850 IU international unit(s)
- Max total dose
- 79800 IU international unit(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB11889MIG · Substance
- Active substance
- Dalteparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 2500 IU international unit(s)
- Max total dose
- 70000 IU international unit(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB03372MIG · Substance
- Active substance
- Nadroparin Calcium
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 5700 IU international unit(s)
- Max total dose
- 159600 IU international unit(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB11889MIG · Substance
- Active substance
- Dalteparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 5000 IU international unit(s)
- Max total dose
- 140000 IU international unit(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25417 · Substance
- Active substance
- Dabigatran
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 220 mg milligram(s)
- Max total dose
- 6160 mg milligram(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB11933MIG · Substance
- Active substance
- Enoxaparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 4000 IU international unit(s)
- Max total dose
- 112000 IU international unit(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB29263 · Substance
- Active substance
- Rivaroxaban
- Pharmaceutical form
- FILM COATED TABLETS
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 280 mg milligram(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25425 · Substance
- Active substance
- Apixaban
- Pharmaceutical form
- FILM COATED TABLETS
- Route of administration
- ORAL
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 140 mg milligram(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB11933MIG · Substance
- Active substance
- Enoxaparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 2000 IU international unit(s)
- Max total dose
- 56000 IU international unit(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 3
SUB181082 · Substance
- Active substance
- Andexanet Alfa
- Pharmaceutical form
- LYOPHILIZED POWDER FOR PREPARATION FOR INJECTION (8)
- Route of administration
- INFUSION
- Max daily dose
- 1760 mg milligram(s)
- Max total dose
- 1760 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cofact 500 IE poeder en oplosmiddel voor oplossing voor injectie.
PRD2291635 · Product
- Active substance
- Human Coagulation Factor Ix
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INFUSION
- Max daily dose
- 2500 U unit(s)
- Max total dose
- 2500 U unit(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD01 — COAGULATION FACTOR IX, II, VII AND X IN COMBINATION
- Marketing authorisation
- RVG 17060
- MA holder
- PROTHYA BIOSOLUTIONS NETHERLANDS B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cofact 250 IE poeder en oplosmiddel voor oplossing voor injectie.
PRD377834 · Product
- Active substance
- Human Coagulation Factor Ix
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INFUSION
- Max daily dose
- 2500 U unit(s)
- Max total dose
- 2500 U unit(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD01 — COAGULATION FACTOR IX, II, VII AND X IN COMBINATION
- Marketing authorisation
- RVG 17060
- MA holder
- PROTHYA BIOSOLUTIONS NETHERLANDS B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Academisch Ziekenhuis Leiden
- Sponsor organisation
- Academisch Ziekenhuis Leiden
- Address
- Albinusdreef 2
- City
- Leiden
- Postcode
- 2333 ZA
- Country
- Netherlands
Scientific contact point
- Organisation
- Academisch Ziekenhuis Leiden
- Contact name
- Study team DISTINCT trial
Public contact point
- Organisation
- Academisch Ziekenhuis Leiden
- Contact name
- Study team DISTINCT trial
Locations
1 EU/EEA country · 15 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 10,078 | 15 |
| Rest of world | — | 0 | — |
Investigational sites
ZorgSaam Ziekenhuis
Orthopedic surgery, Wielingenlaan 2, 4535 PA, Terneuzen
St. Antonius Ziekenhuis
Orthopedic surgery, P. O. Box 2500, 3430 EM, Nieuwegein
Leids Universitair Medisch Centrum (LUMC)
Clinical epidemiology, Albinusdreef 2, 2333 ZA, Leiden
Bergman Clinics Nederland B.V.
Orthopedic surgery, Gooimeer 11, 1411 DE, Naarden
Gelre Hospitals
Orthopedic surgery, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn
Equipe Zorgbedrijven Nederland B.V.
Orthopedic surgery, Flight Forum 130, 5657 DD, Eindhoven
Stichting Elisabeth-Tweesteden Ziekenhuis
Orthopedic surgery, Hilvarenbeekseweg 60, 5022 GC, Tilburg
Stichting St. Anna Zorggroep
Orthopedic surgery, Bogardeind 2, 5664 EH, Geldrop
Reinier Haga Groep Orthopedisch Centrum B.V.
Orthopedic surgery, Toneellaan 2, 2725 NA, Zoetermeer
Stichting OLVG
Orthopedic surgery, Jan Tooropstraat 164, 1061 AE, Amsterdam
Bravis Ziekenhuis
Orthopedic surgery, Boerhaavelaan 25, 4708 AE, Roosendaal
Zuyderland Medisch Centrum Stichting
Orthopedic surgery, Dr. H. Van Der Hoffplein 1, 6162 BG, Geleen
Alrijne Zorggroep Stichting
Orthopedic surgery, Simon Smitweg 1, 2353 GA, Leiderdorp
Isala Klinieken Stichting
Orthopedic surgery, Dokter Van Heesweg 2, 8025 AB, Zwolle
Groene Hart Ziekenhuis
Orthopedic surgery, Bleulandweg 10, 2803 HH, Gouda
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-10-23 | 2024-11-14 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 37 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol 2023-510186-98 | 5.0 |
| Protocol (for publication) | D1_ Protocol 2023-510186-98-00 track-changes | 5.0 |
| Protocol (for publication) | D1_ Protocol supplement 1 literature_review | 1 |
| Protocol (for publication) | D1_ Protocol supplement 2 recruitment considerations | 1 |
| Protocol (for publication) | D1_ Protocol supplement 3 Castor compliance with laws and regulations | 1 |
| Protocol (for publication) | D1_ Protocol supplement 4 monitoring plan | 1 |
| Protocol (for publication) | D1_ Protocol supplement 5 Quality Assurance Plan | 1 |
| Protocol (for publication) | D1_ Supplement 4_Monitoring plan track-changes | 1 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire 12 months | 1 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire 2 weeks | 1 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire 2 weeks track-changes | 1 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire 3 months | 4.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire 3 months track-changes | 4.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire 6 weeks | 4.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire 6 weeks track-changes | 4.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire alternative follow-up 3 months | 1 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire baseline | 1 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire baseline track-changes | 1 |
| Recruitment arrangements (for publication) | K1_ recruitment procedure NL | 1 |
| Recruitment arrangements (for publication) | K2_ Recruitment material flyer | 1 |
| Recruitment arrangements (for publication) | K2_ Recruitment material information website LUMC | 1 |
| Recruitment arrangements (for publication) | K2_ Recruitment material Storyboard Animation video general | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF adults DISTINCT 1 | 3.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF adults DISTINCT 2 | 3.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF adults DISTINCT 3 | 3.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material storyboard animation video DISTINCT1 | 1 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material storyboard animation video DISTINCT2 | 1 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material storyboard animation video DISTINCT3 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Apixaban 2 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Apixaban 2,5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Apixaban 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Dabigatran | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Dalteparin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Enoxaparin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Nadroparin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC Rivaroxaban | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_NL 2023-510186-98 | 1 |
Application history
8 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-29 | Netherlands | Acceptable 2024-08-05
|
2024-08-12 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-09-10 | Netherlands | Acceptable 2024-08-05
|
2024-09-10 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-04 | Netherlands | Acceptable | 2024-11-29 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-13 | Netherlands | Acceptable 2025-03-07
|
2025-03-07 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-05-16 | Netherlands | Acceptable | 2025-06-30 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-07-23 | Netherlands | Acceptable 2025-08-11
|
2025-08-11 |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-10-29 | Netherlands | Acceptable | 2025-11-14 |
| 8 | SUBSTANTIAL MODIFICATION | SM-7 | 2026-03-11 | Netherlands | Acceptable | 2026-03-20 |