Thromboprophylaxis in Lower Limb Immobilisation
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Rivaroxaban, Apixaban, Enoxaparin Injectable Solution, Tinzaparin Injectable Solution.
- Who it may be relevant to
- Registry conditions: Thrombosis, Injury Leg. Basic parameters: from 16 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United Kingdom
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Thromboprophylaxis in Lower Limb Immobilisation (TiLLI): a Multicentre Study Comprising Two Linked Open Label Phase III Randomised Controlled Trials Evaluating the Effectiveness and Cost Effectiveness of Different Methods of Pharmacological Prophylaxis for Patients With Temporary Lower Limb Immobilisation.
Overview
The goal of this clinical trial is to find out the clinical and cost effectiveness of Thromboprophylaxis in participants who have been placed in a plaster cast or splint after injury. The main questions it aims to answer are: * whether giving tablets to people at high risks of clots after a leg injury is as good as injections (standard care) * whether giving any medication after a leg injury is better than standard care (advice only) for people at low risk of clots. Participants will be assessed to be high risk (TiLLI High) or low risk (TiLLI Low). People who are at high risk of clots will have either tablets or injections to reduce their risk. People at low risk will receive tablets, injections or no medication. Drug treatments will be provided for the duration of immobilisation or up to 42 days (whichever is earlier), in accordance with current NICE guidelines. The participants will be followed up for 90 days following randomisation.
Detailed description
People have an increased risk of blood clots when they have a leg injury treated with a plaster cast or a splint, which happens to over 70,000 people every year in the UK. Blood clots can cause long term problems in the legs and can also move to the lungs, causing serious illness and occasionally death. Medicines are available to reduce the risk of blood clots, but they can also increase the risk of bleeding. In people at high risk of clots, most hospitals use the recommended daily injections which can be uncomfortable and sometimes difficult to give. Tablets are available that reduce the risk of blood clots in other groups, but it is not known if tablets work as well as the injections for people with a leg injury. It is also not known whether people at low risk of blood clots may benefit from any medication. As such, a national research body has identified the need for further study on this topic.
The TiLLI study has two aims - to determine whether giving tablets to people at high risk of clots after a leg injury is as good as injections, and whether giving any medication is better than standard care (advice only) for people at low risk of clots.
The TiLLI study consists of two linked trials: TiLLI-High and TiLLI-Low. People who have been placed in a plaster cast or splint after a leg injury will be invited to participate. Those who agree and are at high risk of clots will enter TiLLI-High and be randomised to receive either tablets or injections to reduce their risk of blood clots; those at low risk will enter TiLLI-Low and will be randomised to receive tablets, injections, or no medication. Patients and doctors will know what medication they are taking. All patients will be provided with written guidance on the signs and symptoms of blood clots and advice on managing their medication.
Information will be collected from study participants up to 90 days after joining the study to find out whether anyone suffers blood clots or complications from the medication. This data will be collected by reviewing medical records and contacting participants as needed. To encourage people from different backgrounds to take part, the study will run from lots of different hospitals across the UK. Study materials will be translated into different languages for those who do not speak English. The investigators will collect as much information as possible from people without extra hospital visits. An independent panel will look at the data as the study progresses to decide whether it is safe to continue.
The study will cost approximately £300 per patient, which is excellent value for money. If these trials show that tablets are as effective as injections, approximately 20,000 patients will be able to avoid injections and \>£1.5 million will be released back to NHS resources, every year. When the study is finished, the investigators will share the findings with staff in the NHS, patient charities and national guideline bodies. They will also publish the findings in the medical press and work with international research groups to answer further research questions on this topic.
Interventions
- Drug Rivaroxaban
10mg once daily via oral ingestion - Drug Apixaban
2.5mg twice daily via oral ingestion - Drug Enoxaparin Injectable Solution
40mg once daily via subcutaneous injection - Drug Tinzaparin Injectable Solution
4500 IU once daily via subcutaneous injection - Drug Dalteparin Injectable Solution
5000 IU once daily via subcutaneous injection - Drug Fondaparinux Injectable Product
2.5 mg once daily via subcutaneous injection
Primary outcome measures
- Composite of net clinical benefit comprising clinical VTE event, major bleeding, and cause-specific mortality [Time frame: Within 90 days of randomisation]
Secondary outcome measures (10)
- Symptomatic VTE event occurrence [Time frame: Within 90 days from randomisation]
- Major bleeding occurrence [Time frame: Within 42 days from randomisation]
- Cause-specific mortality occurrence [Time frame: Within 90 days from randomisation]
- Adverse and Serious adverse events [Time frame: Within 90 days from randomisation.]
- Medication adherence [Time frame: Up to 42 days from randomisation]
- Health utility (EQ-5D-5L) [Time frame: Up to 90 days post randomisation.]
- Patient satisfaction regarding the burdens and benefits of anticoagulation [Time frame: Collected within 42 days following randomisation when the participants stops study treatment.]
- Hospital readmission/reattendance [Time frame: Within the first 90 days.]
- Health and social care resource use [Time frame: Within the first 90 days]
- Patient longer term outcome VTE and bleeding data [Time frame: Informed by directly measured events up to 90 days.]
Eligibility criteria
Inclusion criteria
- Age >/= 16 years
- Placed in temporary lower limb immobilisation (rigid cast or brace) as a result an injury that occurred within the last 7 calendar days
Exclusion criteria
- Hospital admission is required direct from the emergency department, minor injuries unit, or fracture clinic setting with an expected length of stay >2 calendar days.
- Absolute contraindication or known hypersensitivity to anticoagulants, including history of end stage renal failure (eGFR <20ml/min/1.73m2), hepatic failure or use of concomitant systemic treatment with azole-antimycotics (such as ketoconazole, itraconazole, voriconazole and posaconazole), HIV protease inhibitors (e.g. ritonavir) or active substances strongly inhibiting elimination pathways such as CYP3A4 or P-gp (such as clarithromycin, erythromycin or dronaderone) or a history of heparin induced thrombocytopenia.
- Pregnancy, actively seeking conception, or active breastfeeding.
- Preceding use of anticoagulant treatment for >3 calendar days at prophylactic or therapeutic dose.
- Prior enrolment in the TiLLI study.
- Non-rigid immobilisation (crepe bandage, tubigrip support, strapping).
- Time since prescription of rigid immobilisation >3 calendar days
- Co-enrolment onto a CTIMP where an anticoagulant is administered
- People lacking the capacity to consent
- Inability or refusal to use acceptable contraception up until after the last administration of IMP. Only applicable for women of childbearing potential who have been randomised to receive apixaban or rivaroxaban
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Prevention
Study locations
United Kingdom · 5 centers
- Epsom and St Helier University Hospitals NHS Trust — Carshalton
- Hull Teaching Hospitals NHS Trust — Hull
- Barts Health NHS Trust — London
- Kings College Hospital NHS Foundation Trust — London
- Northern Care Alliance NHS Foundation Trust — Manchester
Identifiers
NCT: NCT06370273 · 1009305