ThrombosisPhase 3TiLLINCT06370273
Thromboprophylaxis in Lower Limb Immobilisation
A Phase 3 study testing Rivaroxaban, Apixaban and Enoxaparin Injectable Solution in people with Thrombosis and Injury Leg, run by Queen Mary University of London at 5 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Thrombosis, Injury Leg
- What is being tested?
- Rivaroxaban, Apixaban and Enoxaparin Injectable Solution
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10,044 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 12 Nov 2024to 31 Aug 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
Show all 10Show fewer
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United Kingdom5 sites, 5 recruiting
- Recruiting
Epsom and St Helier University Hospitals NHS Trust
Carshalton, Surrey
Rebecca Macfarlane, 01372735735 ext. 6013, ESTH.EDresearch@nhs.net
Rebecca Macfarlane
- Recruiting
Hull Teaching Hospitals NHS Trust
Hull
Jack Preece, MBBS BSc(Hons) PgDIP FRCEM, 07000000000, jack.preece4@nhs.net
- Recruiting
Barts Health NHS Trust
London
Ben Bloom, 02035940045, bartshealth.tmailboxedresearch@nhs.net
Ben Bloom
- Recruiting
Kings College Hospital NHS Foundation Trust
London
Thomas Hester, BSc(Hons) MBBS MRCS PGCert
- Recruiting
Northern Care Alliance NHS Foundation Trust
Manchester
Daniel Horner, 0161 206 2188, acute.research@nca.nhs.uk
Daniel Horner
About this study
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.
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:
Read more
- 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.
Read the 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.
- Conditions
- Thrombosis, Injury Leg
- Being tested
- Rivaroxaban, Apixaban, Enoxaparin Injectable Solution, Tinzaparin Injectable Solution, Dalteparin Injectable Solution
- Medical subject headings
- Thrombosis, Leg Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivaroxabanDrug
10mg once daily via oral ingestion
ApixabanDrug
2.5mg twice daily via oral ingestion
Enoxaparin Injectable SolutionDrug
40mg once daily via subcutaneous injection
Tinzaparin Injectable SolutionDrug
4500 IU once daily via subcutaneous injection
Dalteparin Injectable SolutionDrug
5000 IU once daily via subcutaneous injection
Fondaparinux Injectable ProductDrug
2.5 mg once daily via subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| TiLLI-High Intervention | Active comparator | 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. Receives: Drug: Rivaroxaban; Drug: Apixaban |
| TiLLI-High Routine Care | Active comparator | 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 Receives: Drug: Enoxaparin Injectable Solution; Drug: Tinzaparin Injectable Solution; Drug: Dalteparin Injectable Solution; Drug: Fondaparinux Injectable Product |
| TiLLI-Low Intervention 1 (DOAC) | Active comparator | 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. Receives: Drug: Rivaroxaban; Drug: Apixaban |
| TiLLI-Low Intervention 2 (Parenteral prophylaxis) | Active comparator | 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 Receives: Drug: Enoxaparin Injectable Solution; Drug: Tinzaparin Injectable Solution; Drug: Dalteparin Injectable Solution; Drug: Fondaparinux Injectable Product |
| TiLLI-Low Routine Care | No intervention | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Within 90 days of randomisation
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Within 90 days from randomisation.
Medication adherence
To report participant adherence to allocated anticoagulant verified through digital response system.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Informed by directly measured events up to 90 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2024
- Study start12 Nov 2024
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ThrombosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A pragmatic, open-label, linked pair of randomised controlled trials with common outcomes and parallel economic analysis each with internal pilot phases, conducted across 30 NHS sites
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 10,044 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06370273
- Sponsor's protocol ID
- 1009305
- Acronym
- TiLLI
- Status last verified
- Jul 2026
- First submitted
- 21 Mar 2024
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT06370273
- Acronym / sponsor ID
- TiLLI / 1009305
- Conditions
- Thrombosis, Injury Leg
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10,044 participants (estimated)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- 12 Nov 2024 (actual)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 17 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 5
- Model description
- A pragmatic, open-label, linked pair of randomised controlled trials with common outcomes and parallel economic analysis each with internal pilot phases, conducted across 30 NHS sites
| Arm | Type | Receives |
|---|---|---|
| TiLLI-High Intervention | Active comparator | Drug: Rivaroxaban, Drug: ApixabanA 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. |
| TiLLI-High Routine Care | Active comparator | Drug: Enoxaparin Injectable Solution, Drug: Tinzaparin Injectable Solution, Drug: Dalteparin Injectable Solution, Drug: Fondaparinux Injectable ProductA 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 |
| TiLLI-Low Intervention 1 (DOAC) | Active comparator | Drug: Rivaroxaban, Drug: ApixabanA 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. |
| TiLLI-Low Intervention 2 (Parenteral prophylaxis) | Active comparator | Drug: Enoxaparin Injectable Solution, Drug: Tinzaparin Injectable Solution, Drug: Dalteparin Injectable Solution, Drug: Fondaparinux Injectable ProductA 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 |
| TiLLI-Low Routine Care | No intervention | –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 |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivaroxaban10mg once daily via oral ingestion | Drug | TiLLI-High Intervention, TiLLI-Low Intervention 1 (DOAC) |
| Apixaban2.5mg twice daily via oral ingestion | Drug | TiLLI-High Intervention, TiLLI-Low Intervention 1 (DOAC) |
| Enoxaparin Injectable Solution40mg once daily via subcutaneous injection | Drug | TiLLI-High Routine Care, TiLLI-Low Intervention 2 (Parenteral prophylaxis) |
| Tinzaparin Injectable Solution4500 IU once daily via subcutaneous injection | Drug | TiLLI-High Routine Care, TiLLI-Low Intervention 2 (Parenteral prophylaxis) |
| Dalteparin Injectable Solution5000 IU once daily via subcutaneous injection | Drug | TiLLI-High Routine Care, TiLLI-Low Intervention 2 (Parenteral prophylaxis) |
| Fondaparinux Injectable Product2.5 mg once daily via subcutaneous injection | Drug | TiLLI-High Routine Care, TiLLI-Low Intervention 2 (Parenteral prophylaxis) |
Primary outcome
Composite of net clinical benefit comprising clinical VTE event, major bleeding, and cause-specific mortality
Time frame: Within 90 days of randomisation
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).
10 secondary outcomes
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rivaroxaban, Apixaban and Enoxaparin Injectable Solution in people with Thrombosis and Injury Leg, run by Queen Mary University of London at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Trial Manager (+44 (0) 20 7882 5555, tilli-bjh@qmul.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of net clinical benefit comprising clinical VTE event, major bleeding, and cause-specific mortality (time frame: Within 90 days of randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.