A Phase 3 interventional study of Rivaroxaban and Apixaban in Thrombosis and Injury Leg, sponsored by Queen Mary University of London. Recruiting at 5 sites in United Kingdom. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2026-07-02.
Sponsored by Queen Mary University of London · Phase 3, Interventional, and Prevention
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:
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.
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.
955 studies on the registry are indexed under Thrombosis; 171 are open to participants now.
This study's planned enrollment of 10,044 is above the median of 83 across 530 interventional studies indexed under Thrombosis.
Browse Thrombosis studies →Queen Mary University of London is the lead sponsor of 253 studies on the registry; 58 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A non-inferiority trial in people with temporary lower limb immobilisation at high risk of VTE comparing Direct Oral AntiCoagulants (DOACs) (intervention) to parenteral prophylaxis (routine care). Drug treatments will be provided for the duration of immobilisation or up to 42 days (whichever is earlier), in accordance with current NICE guidance. Intervention medications: Rivaroxaban 10mg once daily via oral ingestion. OR Apixaban 2.5mg twice daily via oral ingestion.
Drug: Rivaroxaban · Drug: Apixaban
A non-inferiority trial in people with temporary lower limb immobilisation at high risk of VTE comparing Direct Oral AntiCoagulants (DOACs) (intervention) to parenteral prophylaxis (routine care). Drug treatments will be provided for the duration of immobilisation or up to 42 days (whichever is earlier), in accordance with current NICE guidance. Routine Care: Enoxaparin 40mg once daily via subcutaneous injection OR Tinzaparin 4500 IU once daily via subcutaneous injection OR Dalteparin 5000 IU once daily via subcutaneous injection OR Fondaparinux 2.5mg once daily via subcutaneous injection
Drug: Enoxaparin Injectable Solution · Drug: Tinzaparin Injectable Solution · Drug: Dalteparin Injectable Solution · Drug: Fondaparinux Injectable Product
A superiority trial in people with temporary lower limb immobilisation at low risk of VTE comparing parenteral prophylaxis (intervention) or Direct Oral AntiCoagulants (DOACs) (intervention) to no pharmacological prophylaxis (routine care). Drug treatments will be provided for the duration of immobilisation or up to 42 days (whichever is earlier), in accordance with current NICE guidance. Intervention medication: DOACs: Rivaroxaban 10mg once daily via oral ingestion. OR Apixaban 2.5mg twice daily via oral ingestion.
Drug: Rivaroxaban · Drug: Apixaban
A superiority trial in people with temporary lower limb immobilisation at low risk of VTE comparing parenteral prophylaxis (intervention) or Direct Oral AntiCoagulants (DOACs) (intervention) to no pharmacological prophylaxis (routine care). Drug treatments will be provided for the duration of immobilisation or up to 42 days (whichever is earlier), in accordance with current NICE guidance. Parenteral prophylaxis: Enoxaparin 40mg once daily via subcutaneous injection OR Tinzaparin 4500 IU once daily via subcutaneous injection OR Dalteparin 5000 IU once daily via subcutaneous injection OR Fondaparinux 2.5mg once daily via subcutaneous injection
Drug: Enoxaparin Injectable Solution · Drug: Tinzaparin Injectable Solution · Drug: Dalteparin Injectable Solution · Drug: Fondaparinux Injectable Product
A superiority trial in people with temporary lower limb immobilisation at low risk of VTE comparing parenteral prophylaxis (intervention) or Direct Oral AntiCoagulants (DOACs) (intervention) to no pharmacological prophylaxis (routine care). Drug treatments will be provided for the duration of immobilisation or up to 42 days (whichever is earlier), in accordance with current NICE guidance. Routine care: No pharmacological prophylaxis
10mg once daily via oral ingestion
2.5mg twice daily via oral ingestion
40mg once daily via subcutaneous injection
4500 IU once daily via subcutaneous injection
5000 IU once daily via subcutaneous injection
2.5 mg once daily via subcutaneous injection
Composite of net clinical benefit comprising clinical VTE event, major bleeding, and cause-specific mortality
To estimate and draw inferences on the difference in a composite outcome of net clinical benefit between treatment groups. A composite primary outcome of net clinical benefit, comprising symptomatic VTE events (any deep vein thrombosis or pulmonary embolism), major bleeding or cause-specific mortality (death from either pulmonary embolus or major bleeding) used as a binary variable ('1' is any event occurred, '0' if none of the events occurred).
Time frame: Within 90 days of randomisation
Symptomatic VTE event occurrence
To compare symptomatic VTE events (any deep vein thrombosis or pulmonary embolism) (an individual component of primary composite outcome) between treatment groups as a binary variable ('1' if any event occurred, '0' if no event occurred). Symptomatic VTE events objectively defined by ISTH criteria.
Time frame: Within 90 days from randomisation
Major bleeding occurrence
To compare major bleeding events (an individual component of primary composite outcome) between treatment groups as a binary variable ('1' if any event occurred, '0' if no event occurred). Major bleeding events objectively defined by ISTH criteria.
Time frame: Within 42 days from randomisation
Cause-specific mortality occurrence
To compare cause-specific mortality events (an individual component of primary composite outcome) between treatment groups as a binary variable ('1' if any event occurred, '0' if no event occurred).
Time frame: Within 90 days from randomisation
Adverse and Serious adverse events
To estimate and draw inferences on the difference in complications (including clinically relevant non-major bleeding and surgical site bleeding) objectively defined by ISTH criteria, between treatment groups.
Time frame: Within 90 days from randomisation.
Medication adherence
To report participant adherence to allocated anticoagulant verified through digital response system.
Time frame: Up to 42 days from randomisation
Health utility (EQ-5D-5L)
To estimate and draw inferences on differences in quality-of-life measures between treatment groups. Using the EuroQol 5 Dimensions 5 Level (EQ-5D-5L), a validated instrument comprising a self-rated health VAS and a five-domain health status questionnaire related to daily activities. Will collect for 4 timepoints: pre injury (completed retrospectively within 7 days following randomisation), 7 days following randomisation, 42 days following randomisation, and 90 days following randomisation
Time frame: Up to 90 days post randomisation.
Patient satisfaction regarding the burdens and benefits of anticoagulation
To estimate and draw inferences on the acceptability of different prophylactic anticoagulants using the validated Anti Clot Treatment Scale (ACTS) for patients allocated to drug treatments. The scale is a 15-item patient-reported instrument of satisfaction with anticoagulation treatment, with separate internal measures of burden and benefits.
Time frame: Collected within 42 days following randomisation when the participants stops study treatment.
Hospital readmission/reattendance
To estimate and draw inferences on the difference in resource use (including hospital readmission/reattendance), cost, quality of life-adjusted survival and relative cost effectiveness between treatment groups. Using bespoke Case Report Forms and review of EHR, research staff to collect information on resources required to deliver subsequent care reviews (including scheduled clinic and unscheduled hospital attendance), and investigations.
Time frame: Within the first 90 days.
Health and social care resource use
To estimate the health and social care resource use and costs and the relative cost effectiveness between treatment groups. Using bespoke Case Report Forms and review of EHR, research staff to collect information on health and social care resource use.
Time frame: Within the first 90 days
Patient longer term outcome VTE and bleeding data
To estimate longer term outcomes, such as post thrombotic syndrome, chronic thromboembolic pulmonary hypertension and bleeding complications and draw inferences on cost effectiveness, by using an existing VTE model with risk-adjusted, population specific effect estimates from this study. This will allow efficient, value for money inferences to made about long-term sequelae of VTE events and determine whether detailed long-term follow-up of participants would be worthwhile. Clinically relevant non-major bleeding events, major bleeding events and symptomatic bleeding events objectively defined by ISTH criteria.
Time frame: Informed by directly measured events up to 90 days.
Plan to share: No
No publications or documents are linked to this record.
Started Nov 2024 (actual). Primary completion is estimated for Aug 2028, 45 months after the start.
Of 27 phase 3 interventional studies under Thrombosis, half reached primary completion within 44 months of starting (the median), counting those still running; a quarter within 26 and three quarters within 57. This study's planned 45 months is close to that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drugs tested here: Rivaroxaban · Apixaban · Enoxaparin · Tinzaparin · Dalteparin · Fondaparinux
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