Opti-Med: A randomised controlled trial of deprescribing to optimise health outcomes for frail older people.

Testing a deprescribing intervention (medication withdrawal algorithm) in which some/all of a the study participant's medications are targeted for withdrawal. One of the two (2) intervention groups will have their medicines over-encapsulated (this will be the BLINDED INTERVENTION group). The other intervention group will have their medicines withdrawn over time without over-encapsulation - ie they will not be blinded (this will be the OPEN INTERVENTION group). Each participant will be enrolled in the study for 12 months and clinical care for all participants will continue under their usual GP/specialists. Both the BLINDED INTERVENTION and OPEN INTERVENTION groups will be treated in the same manner with respect to medication withdrawal. The Medication withdrawal algorithm will be applied by research pharmacists to develop a Medication Withdrawal Plan (MWP) for each participant prior to their allocation to a study group. The MWP is unique for each participant (because of the unique mix of medications each person is taking at baseline). The method used to determine each participant’s MWP will be consistent. Medicines least likely to be of benefit to the participant and least likely to cause adverse drug withdrawal events (ADWE) will be ceased first and those most likely to cause ADWE and/or most likely to provide symptomatic benefit will be tapered slowly and withdrawn last. Up to three medications will be withdrawn simultaneously if unlikely to cause ADWE or if withdrawal effects would be clearly ascribable to the individual drugs. When tapering is required, doses will generally be halved at fortnightly intervals until a dose of half the lowest dose form is reached, following which the medication will be ceased. Some medications with longer half-lives may be tapered to every second and/or every third day dosing until ceased. The total duration of medication withdrawal will depend on the complexity of the participant’s medication regimen and the number of target medicines that are identified. Encapsulation: In the BLINDED INTERVENTION group, we will cease target medications according to the consensus withdrawal plan, as for the OPEN INTERVENTION group. However, medications that can be stopped without dose reduction (e.g. statins, aspirin, vitamins, mineral supplements, bisphosphonates) will be replaced with an (empty) inert placebo capsule. Medications that need to be tapered (e.g., antidepressants, anti-hypertensives, anti-reflux agents) will be encapsulated to maintain blinding. Once the dose has been tapered to zero, an empty inert capsule will continue to be supplied to the participant so that blinding is not compromised. In the BLINDED CONTROL group, the usual dose forms that have been identified as target medicines will be encapsulated at the intervals indicated in the medication withdrawal plan. As this is a residential care population the majority of participants will have their medicines administered by a staff member, promoting adherence to intervention protocols. Adherence and compliance: Contemporaneous, and previous, medication charts will be copied at each participant review to provide a complete medication administration record. Upon trial completion, community pharmacies and RACF will be asked to return any remaining trial medication to the pharmacy supplier. Adherence, compliance, and effectiveness of blinding will be measured by i) counting of unused medicines ii) reconciliation of withdrawal plans with administration records iii) asking cognitively intact participants which group they believe they were allocated to at the conclusion of the twelve month follow up iv) asking RACF nursing staff, the usual treating doctor and blinded research staff which group they believe participants were allocated at the time of the 12 month follow-up. Monitoring of Encapsulation Process and Supply of Study Medications: The research staff will closely monitor for any errors in the supply of usual or study medications at each regular review, and for any errors in medication administration by visual inspection of the administration record to detect omitted or delayed medicines. The DMC will review these at prescribed intervals (the exact intervals will be determined by the DMC once it convenes and ratifies its charter).