Eligibility

Local study conflicts

• Any co-enrollment conflicts

Inclusion Criteria:

• Age 16 years and above
• Placed in temporary lower limb immobilisation (rigid cast or brace) as a result of 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.
• Previous 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.

• * The Acceptable methods of contraception are as follows
• Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, via oral, intravaginal or transdermal route.
• Progestogen-only hormonal contraception associated with inhibition of ovulation via oral, injectable or implantable route.
• Intrauterine device
• Intrauterine hormone releasing system
• Bilateral tubal occlusion
• Vasectomised partner
• Sexual abstinence
• Male or female condom with or without spermicide
• Cap diaphragm or sponge with spermicide

If the patient is eligible:

Step by Step Guide to Recruitment:

In the working hours of the research team:

• Monday-Friday 07:30 – 18:30


• Contact the EMROx research team on:
  Mobile 0776818242
  Tel 01865 222003
  Bleep 6680

Out of hours and weekends:

Eligibility

• Establish risk strata (TiLLI- High v TiLLI-Low): use the modified TRIP (cast) in the OpenClinica database OpenClinica website
• The database will calculate and assign participant to TiLLI-High or TiLLI-low:
• Low Risk: TiLLI Low - Trip cast < 6
• High Risk: TiLLI Low - Trip cast > 6
• (PI or appropriately trained delegate may override allocation to Tilli-Low if they believe Participant to be high risk.

Gather documentation

• Participant/Patient Information Sheet (PIS) are available in 2 formats Paper & Video.
  Translated PIS is available in Punjabi, Romanian & Polish languages
• Paper PIS is accessible via sharepoint here; "Tilli Recruitment Documents (Trust login required)
• Provide patient with Tilli-High PIS & ICF if the TRIP CAST Score is ≥6
  OR
• Provide patient with Tilli-Low PIS & ICF if the TRIP CAST Score is < 6
• Video PIS: High or Low is accessible via Welcome to TiLLI - please choose a study. Translated PIS is available in Punjabi, Romanian & Polish languages


• Informed Consent Form (ICF) are available in 2 formats Paper and Electronic.
• Paper Informed Consent Form (ICF) is accessible via share point Tilli Recruitment Documents. Provide patient with:
• Tilli-High ICF if the TRIP CAST Score is ≥6
  OR
• Tilli-Low ICF if the TRIP CAST Score is < 6
• Electronic Consent form is available via: https://pctu.openclinica.io/OpenClinica/MainMenu. Access is via individual login account

Formal consent process

Only those with capacity will be enrolled to Tilli.

• Discuss the study with the patient. Provide patient with PIS and ICF. Give ample time to decide. Answer all questions.
• Delegated doctor seeks patient consent. Delegation log can be access through this link: EMROx study delegation log .
• Document in EPR the consent process. Using Power Note: ED Research /Tilli Enrolment (for Clinicians only. Research Nurses use the standard EMROx Tilli EPR Template.)
• If paper ICF was used make sure to give patient copy of the signed ICF. Research Team to retrospectively upload in EPR the signed ICF and PIS.
• Leave the sign paper ICF in the post box.

Electronic eligibility confirmation:

• Delegated doctor confirms eligibility https://pctu.openclinica.io/OpenClinica/MainMenu. This is an individual access.

Randomisation procedure

• Tilli randomisation is done through https://www.sealedenvelope.com/access/. This is accessed with individual login

Carrying out the intervention:

Prescription procedure

• Only delegated doctors can prescribe the study drug.
• Go to EPR. Open Request and Prescribing. Choose "Tilli Clinical Trial Future State Power Plan". Under ACTION is a drop-down list choose "Prescribe Now".
• In Hours Pharmacy:
  Inform pharmacy by calling 21502 that you have prescribed the Tilli Study drug. Give patient the Oxford University Hospitals TiLLI Prescription Request Form and send patient to Level 2 Pharmacy JRH.
• Out of hours pharmacy:
  Patient either comes back to JRH next working day or gets the prescription from out of hospital pharmacy.
  • Patient coming back to JRH: Inform pharmacy calling 21502 that you have prescribed the Tilli Study drug. Give patient the Oxford University Hospitals TiLLI Prescription Request Form. Instruct patient to go to Level 2 Pharmacy JRH the next working day to collect their medication.
  • Patient getting medication from out of hospital pharmacy:
    • Give the patient their first dose of medication stat prior to discharge.
    • Provide FP10 and expense claim form accessible via this link Tilli Recruitment Documents (Trust login required).
• Once recruited provide patients with these documents. Documents can be accessible via this link Tilli Recruitment Documents (Trust login required)
  • Tilli Participant Card
  • Tilli Participant user guide for Medication Groups:
  • DALTEPARIN ARM:
  • Dalteparin Patient Information Sheet can be sourced from ENP Patient Information Leaflet display board out ENP office.
  • Teach the patient how to inject and dispose sharps
  • Provide sharps Bin
  • DOAC ARM
  • Provide patient DOAC information leaflet can be found in Tilli Recruitment Documents (Trust access requires)
  • OR
    
  • Tilli Participant user guide for Medical Advice only (no meds)
  
  
  • Additional Information for if the recruit will undergo surgery
    • Tilli Perioperative guidance Info Participant
    • Tilli Perioperative guidance -General
    • Tilli Perioperative guide- Info Clinicians
  • Tilli GP letter- this can be sent by the research team.

If you have issue accessing the study documents and delegation log links please message the team via WhatsApp: ED Research or scan this QR code

Disposition and follow-up:

If admitted:

• If admitted: Patient will be followed up on a regular basis whilst in patient.

If discharged, provide:

• The patient information sheet and a copy of signed informed consent form.
• GP letter to inform GP of patient’s study participation.
• The study follow-up plan: The research nurses will call the patient day 7, 42 and 90. The Clinical trial unit will send via text or email whichever the patient prefers their adherence and weight-bearing questionnaires
• All/any clinical/medical follow up the patient needs will be the responsibility of the treating clinicians to arrange.
• All standard safety net advice
• A patient card with contact number to call in normal working hours. At weekends and nighttime they would have to call 999 or 111.

Links for further information:

Link to trial site

Link to Tilli study summary video: Available in English, Polish, Romanian, Punjabi:
Click "Info for patients"

Link to Tilli Participant information:Available in English, Polish, Romanian, Punjabi:TILLI-high or TILLI-low arms More Information for VTE: