Less Is More: Optimized Pharmacotherapy With Improved coNtinuity of CarE in hospitaLized oLder peOple

Rationale: Polypharmacy poses an ongoing healthcare challenge, as it is associated with negative outcomes such as adverse drug events, lower quality of life and mortality. These risks are especially elevated for the frail and old, leading to high numbers of drug related admissions (DRAs) and unplanned emergency department visits. Approximately half of the DRAs are potentially preventable, and therefore a possible target point for interventions. Unfortunately, until now, despite multiple efforts to decrease drug related harm, the number of drug related admissions has not decreased. Several studies have previously investigated the effect of a structured medication review with varying success. Identified strengths were multicomponent approaches, multidisciplinary approaches and selection of specifically high-risk patients. The LIMONCELLO study will take this into account and will study a multidisciplinary multicomponent intervention with focus on transitional care in a patient population that is most likely to benefit from this intervention. It is hypothesised that transitional multidisciplinary pharmacotherapeutic care (TMPC) is superior in preventing drug related readmissions (DRreAs) compared to usual care.

Objective: The LIMONCELLO study aims to assess the effect and cost-effectiveness of TMPC compared to usual care.

Study design: This is a cluster randomised controlled trial, a cluster will be defined at the hospital level, with each cluster randomly allocated to the intervention or control group. Patients aged 70 years or older with polypharmacy, admitted to the hospital via the emergency department for longer than 24 hours, with completed medication verification and with an elevated risk of drug related readmissions (calculated by use of the DRA prediction model, an algorithm developed by the OPERAM study group) will be included. Participants in intervention hospitals will receive TMPC during index hospitalisation. TMPC consists of four elements: pharmacotherapeutic analysis, transitional multidisciplinary discussion, pharmacotherapeutic care interview and discussion with the patient, and a discharge note with the pharmacotherapeutic care plan. The comparator is usual care as is provided in the participating hospitals. Follow-up will be 1 year, participants will be called 30 days, 3 months and 12 months after index hospitalisation.

Statistical considerations: 16 clusters will participate in the study, requiring a total of 161 patients per cluster to be included, 2,576 participants in total. Results will be analysed by intention-to-treat analysis and per-protocol analysis. For the primary outcome, drug related readmissions, a generalized linear mixed model with a binomial distribution and logit link function will be used for the analysis on an individual level, adjusting for clustering.

Inclusion criteria

• 70 years or older
• Polypharmacy, the use of 5 or more regular medications, defined as authorised medications with registration numbers, used for more than 30 days. Topical preparations are excluded from this definition.
• Admitted to hospital through the ED (which comprises both the general emergency department and the cardiac emergency department)
• Length of hospitalisation more than 24 hours
• Completed medication verification
• DRA prediction percentage of 23.0% or higher

Exclusion criteria

• No informed consent by patient or a legal representative
• Participation in an interfering clinical trial
• Elective hospital admission
• Direct admission to the ICU (when medication verification as usual can't be executed, and therefore inclusion of patients as described in 10.2 is not possible)
• A life expectancy of less than 3 months, which includes patients with palliative treatment at home, direct admission to palliative care or palliative care planned within 24 hours after index hospital admission.
• Patient or legal representative not able to speak Dutch.
• Follow-up of patient primarily by secondary caregivers. This refers to situations where the secondary caregiver is in the lead of the medication list of the patient instead of the GP or elderly care physician, for example in the following patient groups:

• patients receiving intensive oncologic therapy
• patients in an organ- or stem cell transplantation procedure
• patients receiving intensive (chronic) psychiatric care, such as patients admitted to a medical psychiatric unit
• patients on dialysis