TILE pilot trial study protocol: Tinzaparin Lead-in to Prevent the Post-Thrombotic syndrome study protocol

BMJ Open. 2023 Oct 31;13(10):e064715. doi: 10.1136/bmjopen-2022-064715.


Introduction: The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency due to a prior ipsilateral deep venous thrombosis (DVT). This is a frequent complication that develops in 20%-50% of patients after a proximal DVT and is associated with significant healthcare, economic and societal consequences. In the absence of effective and well-tolerated treatment options for established PTS, effective preventative measures are needed. Anticoagulation itself reduces the risk of PTS, and low-molecular-weight heparin may reduce this further through anti-inflammatory properties targeting the initial acute inflammatory phase of DVT.

Methods and analysis: The Tinzaparin Lead-In to Prevent the Post-Thrombotic syndrome pilot trial is an investigator-initiated, multicentre, open-label assessor-blinded trial that will randomise patients with first acute symptomatic common femoral or iliac DVT to receive either a 3-week lead-in course of tinzaparin, followed by rivaroxaban (experimental arm) or rivaroxaban alone (control arm). Its primary objectives are to assess: (1) proportion of PTS at 6 months using the Villalta scale and (2) study feasibility, which consists of (a) the proportion of screened patients eligible for the study, (2) the proportion of eligible patients recruited and (c) the proportion of recruited patients adherent to treatment (defined as at least 80% of drug taken). This study will determine the feasibility of a subsequent larger definitive trial. Secondary outcomes include change of quality of life scores, PTS severity, global improvement, patient satisfaction, bleeding, recurrent venous thromboembolism, leg pain, death and lost to follow-up. Target recruitment will be a total of 60 participants, recruited at 5-6 centres.

Ethics and dissemination: Primary ethics approval was received from the Sunnybrook Health Sciences Center Research Ethics Board (approval ID 3315). Results of the study will be disseminated via peer-reviewed presentation at scientific conferences and open access publication.

Trial registration number: NCT04794569.

Keywords: Anticoagulation; HAEMATOLOGY; Thromboembolism.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / adverse effects
  • Humans
  • Multicenter Studies as Topic
  • Pilot Projects
  • Postthrombotic Syndrome* / etiology
  • Postthrombotic Syndrome* / prevention & control
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Rivaroxaban / therapeutic use
  • Tinzaparin
  • Treatment Outcome
  • Venous Thromboembolism* / drug therapy


  • Anticoagulants
  • Rivaroxaban
  • Tinzaparin

Associated data

  • ClinicalTrials.gov/NCT04794569

Grants and funding