Not Yet RecruitingPhase 3Phase 4ACTRN12613001376730

Investigating a new approach to re-starting Warfarin after Surgery

A prospective, randomised comparison in hospitalised patients re-commenced on warfarin post-operatively at the usual maintenance dose versus a loading dose strategy to assess time to a stable therapeutic INR.


Sponsor

Flinders Medical Centre

Enrollment

186 participants

Start Date

May 1, 2014

Study Type

Interventional

Conditions

Summary

The blood thinner warfarin is stopped prior to elective surgery for safety reasons. Immediately after the operation it is re-commenced at the usual dose, but takes a week or longer to become therapeutic again (until the blood is thinned out again). This means the patient has to be followed at home by extended care services and injected with a faster acting blood thinner until the warfarin becomes therapeutic again. Some modelling using existing data indicates that if we know the usual warfarin dose of the patient, we may be able to develop a more rapid-acting loading dose strategy that shortens the time for the warfarin to become therapeutic again. This would mean the hospital services wouldn't need to follow the patient for as long, and the patient wouldn't need as many blood thinner injections before their warfarin was therapeutic again.


Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 100 Yearss

Inclusion Criteria1

  • > 18 years old, receiving ongoing warfarin therapy, undergoing elective surgery, able to provide written, informed consent, and followed-up by Hospital-at-Home services for INR monitoring

Exclusion Criteria10

  • Unable to provide written, informed consent
  • Not followed-up by Hospital-at-Home until a stable therapeutic INR is achieved
  • Undergoing cardiac surgery (note – patients with pre-existing artificial mitral or aortic valves are eligible as long as the surgery is not cardiac)
  • Surgery expected to grossly prevent normal oral intake in the week post-operatively eg colon resection
  • Use of more than 2 mg of vitamin K, fresh frozen plasma, or Prothrombinex-VT for INR reversal immediately pre-operatively
  • Use of any vitamin K, fresh frozen plasma, or Prothrombinex for INR reversal in the week after surgery, prior to a stable therapeutic INR being achieved. Normal blood transfusions are permissible and will be considered as a sub-group.
  • Commencement of regular therapy with drugs known to interact with warfarin in the period between the most recently measured maintenance INR and the commencement of surgery, excluding routine drugs administered immediately prior to surgery, such as antibiotic prophylaxis. This includes, imidazole antifungals, macrolide antibiotics, fluoroquinolones, amiodarone, omeprazole, metronidazole, cholestyramine, carbamazepine, phenytoin, barbiturates, rifampicin, sulfamethoxizole/trimpethoprim, SSRI’s, thyroxine, NSAIDs.
  • Lack of reliable INR results with corresponding maintenance dose
  • Most recent routine maintenance dose INR below 1.5 or above 3.5 for patients with a therapeutic range of 2-3, or above 4.0 for patients with a therapeutic range of 2.5-3.5
  • Warfarin reversed during warfarin re-commencement period due to unexpected return to theatre

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Interventions

Guidelines uniformly recommend pre-operative cessation/reversal of the anticoagulant warfarin to ensure an INR <1.5 prior to surgery. Warfarin is recommenced orally on the night of surgery at the prio

Guidelines uniformly recommend pre-operative cessation/reversal of the anticoagulant warfarin to ensure an INR <1.5 prior to surgery. Warfarin is recommenced orally on the night of surgery at the prior known maintenance dose. The patient has often been discharged prior to achieving a stable therapeutic INR, and is commonly followed by a hospital-based extended care service until this occurs. This requires daily point-of-care INR monitoring and bridging anticoagulation, usually with a low-molecular weight heparin. This study utilises the fact that the response to a warfarin loading dose is proportional to the maintenance dose to explore the utility of a structured loading dose strategy in these patients to shorten the time to re-achieve a stable therapeutic INR. This would decrease the use of bridging anticoagulation and shorten the length-of-stay under extended care services. The oral loading dose strategy uses twice the Standardised Maintenance Dose daily for the first 3 days of re-commencement (commencing on the night of surgery) and returning to the normal maintenance dose on the 4th day, where the Standardised Maintenance Dose is 2.5 x current dose / current INR. The new loading dose strategy will be compared to current guideline recommendations in a non-blinded, randomised study. Medication adherence will not be monitored.


Locations(2)

Flinders Medical Centre - Bedford Park

SA, Australia

Repatriation Hospital - Daw Park

SA, Australia

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ACTRN12613001376730