A Prospective Study to Assess the Risk Factors That Contribute to Thrombosis in Patients With Lower Limb Injuries. (TILLIRI)

A Prospective Multicentre Study to Assess the Risk Factors That Contribute to Thrombosis in Patients With Lower Limb Injuries (R)Requiring Immobilisation to Identify High Risk Patients Requiring Thromboprophylaxis.

• This study is aimed at identifying patients at high risk for Venous Thrombo-Embolism (VTE) (clots in the veins of legs or clots in the lungs) who have lower limb injuries treated with immobilisation of the lower limb. The study aims to identify high risk patients, who may benefit from thromboprophylaxis (blood thinning medication) to prevent such clots forming.
• To do this we will collect data on 3500 patients who present with lower limb injury requiring immobilisation to the Emergency Departments of the six hospitals named.
• We will assess their risk factors for venous thrombosis at the time of presentation and contact them at twelve weeks to assess if they have had a VTE in order to develop a risk scoring system which can be used to predict the likelihood of VTE development
• This risk scoring system can then be used to identify high risk patients who may benefit from thromboprophylaxis.

Study Overview

• Status: Recruiting
• Conditions: Thromboses, Venous; Lower Limb Injury

Detailed Description

Currently, there is wide variation in the provision of venous thromboembolism (VTE) prophylaxis for patients who suffer lower limb trauma and require lower limb immobilisation. Current United Kingdom guidelines recommend assessing competing risks of VTE and bleeding followed by shared decision-making with the patient on prescription of pharmacological thromboprophylaxis (VTE thromboprophylaxis). However, current American College of Chest Physicians (ACCP) guidelines do not recommend VTE thromboprophylaxis for this group. The largest study carried out to date, the Prevention of Thrombosis after Lower Leg Plaster Cast (POT-CAST) randomised controlled trial 1 identified a very low rate of VTE (1.8%) in the non-intervention arm. This study concluded that thromboprophylaxis was not justified for patients with lower limb trauma who required lower limb immobilisation. However, it recommended that further studies are required to see if it is possible to identify a high risk cohort of patients who may benefit from VTE thromboprophylaxis. No large prospective study has been published to date to assess if it is possible to identify this high risk group.

The Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study was a case-control study designed to identify risk factors for a first VTE. A sub-analysis of this study reviewed 230 patients who had lower limb trauma with cast immobilisation who developed VTE. Based on this data a risk assessment score was derived (termed "L-TRiP" [Leiden-Thrombosis Risk Prediction for patients with cast immobilization] score) in order to identify high risk patients who may benefit from VTE prophylaxis. However, this risk assessment tool has not been prospectively validated in a study.

We have carried out a pilot study to assess the feasibility of a large scale, adequately powered multi-centre study aimed at prospective identification of a high VTE-risk group of patients. This study was presented at the International Society on Thrombosis and Haemostasis meeting in Berlin in 2017.5 Utilizing data from this pilot study, we now aim to perform a multi-centre study with sufficient power to determine whether it is feasible to identify a high risk group of patients with lower limb trauma requiring immobilisation who will benefit from thromboprophylaxis The POT-CAST study determined that the rate of venous thrombo-embolism (VTE) in patients with lower limb trauma requiring a cast was 1.8%. This low rate does not justify VTE prophylaxis for all patients who require a cast. However there may be a high risk group with a rate of VTE high enough to suggest that consideration of VTE prophylaxis may be appropriate. This study will prospectively gather risk factor data on patients at the time of initial presentation post trauma with follow up at 12 weeks to identify those patients who have experienced a symptomatic VTE episode. This data will then be used to identify a group with a high VTE risk which future studies can utilise to target this high risk group to assess if VTE prophylaxis is of benefit.

• Study Type: Observational
• Enrollment (Anticipated): 3500

Contacts and Locations

• Study Contact: Name: denis okeeffe, MBBCH; Phone Number: 00353868049118; Email: denis.okeeffe@hse.ie
• Study Contact Backup: Name: Michael Watts, MD; Phone Number: 00353889865154; Email: Michael.Watts@hse.ie

Study Locations

• Ireland
  • Limerick, Ireland, V94YVHO
    • Recruiting
    • Denis OKeeffe
    • Contact: denis okeeffe, MBBCH; Phone Number: 00353868049118; Email: denis.okeeffe@hse.ie
    • Contact: michael watts, MD; Phone Number: 00353879865154; Email: Michael.Watts@hse.ie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients who present to the Emergency Departments of participating centres with lower limb injury over 18 requiring lower limb immobilisation.

Description

Inclusion Criteria:

• All patients who present to the Emergency Department with lower limb trauma requiring lower limb immobilisation. Aged over 18

Exclusion Criteria:

Patient unable to give consent Previous Venous thromboembolism

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Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the number of patients who develop venous thromboembolism within a 12 week period after a lower limb injury requiring immobilisation	All patients who present to the emergency department with lower limb injury ,require lower limb immobilisation and consent to the study will be enrolled in the study. At 12 weeks we will measure the number of patients who have developed a symptomatic venous thromboembolism confirmed by scanning to measure the rate of VTE in this population group.	12 weeks post trauma and lower limb immobilisation
The identification and measurement of the risk factors that contribute to the development of venous thromboembolism in patients with lower limb injury requiring immobilisation	To record in each participant individual thrombosis risk factors based on the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study ( MEGA study) . To identify which of these factors are significantly associated with the development of venous thromboembolism in this population group.	12 weeks post trauma and immobilisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify a high risk group that will benefit from chemical prophylaxis	To combine the individual measured risk factors to develop a score that will identify a group of participants who are at high risk of thrombosis and will benefit from chemical prophylaxis	12 weeks post trauma and immobilisation

Collaborators and Investigators

• Sponsor: University of Limerick
• Investigators: Principal Investigator: denis okeeffe, MBBCH, University of Limerick

Publications and helpful links

General Publications

• van Adrichem RA, Nemeth B, Algra A, le Cessie S, Rosendaal FR, Schipper IB, Nelissen RGHH, Cannegieter SC; POT-KAST and POT-CAST Group. Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting. N Engl J Med. 2017 Feb 9;376(6):515-525. doi: 10.1056/NEJMoa1613303. Epub 2016 Dec 3.
• Guyatt GH, Akl EA, Crowther M, Schünemann HJ, Gutterman DD, Lewis SZ. Introduction to the ninth edition: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):48S-52S. doi: 10.1378/chest.11-2286.
• Nemeth B, van Adrichem RA, van Hylckama Vlieg A, Bucciarelli P, Martinelli I, Baglin T, Rosendaal FR, le Cessie S, Cannegieter SC. Venous Thrombosis Risk after Cast Immobilization of the Lower Extremity: Derivation and Validation of a Clinical Prediction Score, L-TRiP(cast), in Three Population-Based Case-Control Studies. PLoS Med. 2015 Nov 10;12(11):e1001899; discussion e1001899. doi: 10.1371/journal.pmed.1001899. eCollection 2015 Nov.
• Ocak G, Vossen CY, Verduijn M, Dekker FW, Rosendaal FR, Cannegieter SC, Lijfering WM. Risk of venous thrombosis in patients with major illnesses: results from the MEGA study. J Thromb Haemost. 2013 Jan;11(1):116-23. doi: 10.1111/jth.12043.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 29, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Venous thromboembolism prophylaxis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Wounds and Injuries; Thrombosis; Venous Thrombosis; Leg Injuries
• Other Study ID Numbers: TILLIRI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All researchers will input their centre patient data. The overall committee will review all patient data for review purposes . Individual centres will not be able to access other centres data.
• IPD Sharing Time Frame: At the end of trial for a limited time.
• IPD Sharing Access Criteria: Only the reviewing committee will have access to all data. Individual centres will have access to their centres data.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No