BMJ Open (Mar 2024)
Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial
- ,
- Saskia le Cessie,
- Nick van Es,
- Michiel Coppens,
- Karina Meijer,
- Suzanne C Cannegieter,
- Saskia Middeldorp,
- Menno V Huisman,
- Frederikus A Klok,
- Geert-Jan Geersing,
- Annette W G van der Velden,
- Elske M van den Akker-van Marle,
- Albert T A Mairuhu,
- M Elske van den Akker-van Marle,
- Laura M Faber,
- Saskia le Cessie,
- Tjerk de Nijs,
- Remy H H Bemelmans,
- Coen van Guldener,
- Marcel A van de Ree,
- Marieke J.H. Wermer,
- Tessa Elling,
- Carolien van Netten,
- Milou A M Stals,
- Rick Roos,
- J Louise I Burggraaf-van Delft,
- Nienke van Rein,
- Jan-Willem K van den Berg,
- Coty Y Bruggeman,
- Marissa Cloos-van Balen,
- Matthijs Eefting,
- Yvonne Ende-Verhaar,
- Wouter K de Jong,
- Fleur Kleijwegt,
- Ted Koster,
- Cees Kroon,
- Saskia Kuipers,
- Jenneke Leentjens,
- Dieuwke Luijten,
- Ilse Schrover,
- Janneke Swart-Heikens,
- Yavuz Bilgin,
- Marleen Goddrie,
- Pieter Jobse,
- Suzanne Jong,
- Brianne Murphy,
- Carla Boekholt,
- Danick Werner,
- Laura Kratz,
- Marjolein Kremers,
- Monique Schilders,
- Gideon Hajer,
- Bas Langeveld,
- Saskia Teunisse-de Recht,
- Annemiek Bogerd,
- Ymke Broers,
- Stan Kolman,
- Sanjay Sankatsing,
- Lenneke van Tol,
- Edith Beishuizen,
- Shantie Bharatsingh,
- Edith Boersma,
- Annemarie van der Kraan-Donker,
- Sabine van Arnhem,
- Fransien Croon-de Boer,
- Ad Dees,
- J P (Hanneke) van Embden,
- Roxane Heller,
- Merel Hoogendorp,
- Roel Jonkhoff,
- Roel J J M van de Laar,
- Corry Leunis-de Ruiter,
- Patricia Scherpenisse-Klopstra,
- Tom L H Stellema,
- Kim Warink,
- Lizanne E van den Akker,
- Eleonora C Camilleri,
- Tess R C Huibregtse,
- Ingeborg de Jonge,
- Ruben Y Kok,
- Inger N Kunnekes,
- Lejla Mahic,
- Hinke C Nagtegaal,
- Petra J Noordijk,
- Hülya Oztürk,
- Alexia M van der Ploeg,
- Nienke van Rein,
- Vibeke Schmidt,
- Anne-Marie Schuitemaker,
- Vera C Slootweg,
- Mark J R Smeets,
- Milou Thibaudier,
- Marco Dam,
- Swopkje de Jong,
- Hanneke van der Velde,
- Evertine Abbink,
- Carlinda Bresser,
- Simone Sissing,
- Soerajja Bhoelan,
- Èmese Heijkoop,
- Francien Huisman,
- Mark Lenssen,
- Anja B U Makelburg,
- Karen H Thedinga,
- Marja A J Voskuilen,
- Femke Yspeerd,
- Sandra Brookman,
- Titia Lamberts,
- Inge Paas,
- Janneke Swart Heikens,
- Janneke van den Brink,
- Wouter K de Jong,
- Aline van de Vendel,
- Ellis S. van Etten
Affiliations
- Antimicrobial Resistance Research Group, Centre for Neonatal and Paediatric Infection, St George`s University of London, London, UK
- Saskia le Cessie
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Nick van Es
- Department of Vascular Medicine, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, The Netherlands
- Michiel Coppens
- Department of Vascular Medicine, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, The Netherlands
- Karina Meijer
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Suzanne C Cannegieter
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Saskia Middeldorp
- Department of Internal Medicine, Radboud university medical center, Nijmegen, Gelderland, The Netherlands
- Menno V Huisman
- Department of Medicine-Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Frederikus A Klok
- Department of Medicine-Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Geert-Jan Geersing
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Annette W G van der Velden
- Department of Internal Medicine, Martini Ziekenhuis, Groningen, Groningen, The Netherlands
- Elske M van den Akker-van Marle
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Albert T A Mairuhu
- Department of Internal Medicine, Haga Hospital, Den Haag, Zuid-Holland, The Netherlands
- M Elske van den Akker-van Marle
- Laura M Faber
- Saskia le Cessie
- Tjerk de Nijs
- Remy H H Bemelmans
- Department of Internal Medicine, Ziekenhuis Gelderse Vallei, Ede, Gelderland, The Netherlands
- Coen van Guldener
- Department of Internal Medicine, Amphia Ziekenhuis, Breda, North Brabant, The Netherlands
- Marcel A van de Ree
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Marieke J.H. Wermer
- Tessa Elling
- Carolien van Netten
- Milou A M Stals
- Rick Roos
- Department of Internal Medicine, Haga Hospital, Den Haag, Zuid-Holland, The Netherlands
- J Louise I Burggraaf-van Delft
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Nienke van Rein
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Jan-Willem K van den Berg
- Department of Pulmonology, Isala Klinieken, Zwolle, Overijssel, The Netherlands
- Coty Y Bruggeman
- Department of Internal Medicine, Martini Ziekenhuis, Groningen, Groningen, The Netherlands
- Marissa Cloos-van Balen
- Department of Internal Medicine, Groene Hart Ziekenhuis, Gouda, Zuid-Holland, The Netherlands
- Matthijs Eefting
- Department of Internal Medicine, Ikazia Ziekenhuis, Rotterdam, Zuid-Holland, The Netherlands
- Yvonne Ende-Verhaar
- Department of Internal Medicine, Medisch Centrum Haaglanden, Den Haag, Zuid-Holland, The Netherlands
- Wouter K de Jong
- Department of Pulmonology, Ziekenhuis Gelderse Vallei, Ede, Gelderland, The Netherlands
- Fleur Kleijwegt
- Department of Internal Medicine, Rode Kruis Ziekenhuis, Beverwijk, Noord-Holland, The Netherlands
- Ted Koster
- Department of Internal Medicine, Groene Hart Ziekenhuis, Gouda, Zuid-Holland, The Netherlands
- Cees Kroon
- Department of Internal Medicine, Ziekenhuis Nij Smellinghe, Drachten, Friesland, The Netherlands
- Saskia Kuipers
- Department of Internal Medicine, ADRZ, Goes, Zeeland, The Netherlands
- Jenneke Leentjens
- Department of Internal Medicine, Radboud university medical center, Nijmegen, Gelderland, The Netherlands
- Dieuwke Luijten
- Department of Medicine-Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Ilse Schrover
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Janneke Swart-Heikens
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Yavuz Bilgin
- Marleen Goddrie
- Pieter Jobse
- Suzanne Jong
- Brianne Murphy
- Carla Boekholt
- Danick Werner
- Laura Kratz
- Marjolein Kremers
- Monique Schilders
- Gideon Hajer
- Bas Langeveld
- Saskia Teunisse-de Recht
- Annemiek Bogerd
- Ymke Broers
- Stan Kolman
- Sanjay Sankatsing
- Lenneke van Tol
- Edith Beishuizen
- Shantie Bharatsingh
- Edith Boersma
- Annemarie van der Kraan-Donker
- Sabine van Arnhem
- Fransien Croon-de Boer
- Ad Dees
- J P (Hanneke) van Embden
- Roxane Heller
- Merel Hoogendorp
- Roel Jonkhoff
- Roel J J M van de Laar
- Corry Leunis-de Ruiter
- Patricia Scherpenisse-Klopstra
- Tom L H Stellema
- Kim Warink
- Lizanne E van den Akker
- Eleonora C Camilleri
- Tess R C Huibregtse
- Ingeborg de Jonge
- Ruben Y Kok
- Inger N Kunnekes
- Lejla Mahic
- Hinke C Nagtegaal
- Petra J Noordijk
- Hülya Oztürk
- Alexia M van der Ploeg
- Nienke van Rein
- Vibeke Schmidt
- Anne-Marie Schuitemaker
- Vera C Slootweg
- Mark J R Smeets
- Milou Thibaudier
- Marco Dam
- Swopkje de Jong
- Hanneke van der Velde
- Evertine Abbink
- Carlinda Bresser
- Simone Sissing
- Soerajja Bhoelan
- Èmese Heijkoop
- Francien Huisman
- Mark Lenssen
- Anja B U Makelburg
- Karen H Thedinga
- Marja A J Voskuilen
- Femke Yspeerd
- Sandra Brookman
- Titia Lamberts
- Inge Paas
- Janneke Swart Heikens
- Janneke van den Brink
- Wouter K de Jong
- Aline van de Vendel
- Ellis S. van Etten
- DOI
- https://doi.org/10.1136/bmjopen-2023-078676
- Journal volume & issue
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Vol. 14,
no. 3
Abstract
Introduction Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks.Methods and analysis The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients.Ethics and dissemination The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences.Trial registration number NCT06087952.
