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

Study Overview
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Brief Summary
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The goal of this cluster randomized controlled trial is to compare transitional multidisciplinary pharmacotherapeutic care (TMPC) with usual care in patients aged 70 years or older with polypharmacy, admitted to the hospital via the emergency department for longer than 24 hours and that have an elevated risk of drug related readmissions. The primary aims of the study are: To assess whether TMPC leads to a decrease in number of DRreAs compared to usual care during the first 30 days after index hospitalisation. To assess whether TMPC is cost-effective Participants will receive TMPC in hospitals allocated to the intervention. TMPC will be executed by a pharmacotherapeutic team, it consists of the following four elements: pharmacotherapeutic analysis transitional multidisciplinary discussion pharmacotherapeutic care interview and discussion with the patient discharge note with the pharmacotherapeutic care plan Researchers will compare TMPC with usual care to assess the effect and cost-effectiveness of TMPC.

Detailed Description
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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.

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

Conditions
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Polypharmacy, Medication Review

Intervention / Treatment
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* Other: Transitional Multidisciplinary Pharmacotherapeutic Care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cluster randomized study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transitional Multidisciplinary Pharmacotherapeutic Care (TMPC)<br>The participants in hospitals allocated to the intervention arm will receive TMPC, which will be executed by a Pharmacotherapy-team and will take place during the index hospital stay. This Pharmacotherapy-team will be composed of a physician and a hospital pharmacist, preferably registered as clinical pharmacologists. | Other: Transitional Multidisciplinary Pharmacotherapeutic Care<br>* A structured medication review with improved transitional care and multidisciplinary collaboration. TMPC consists of the following four elements: A structured pharmacotherapeutic analysis A transitional multidisciplinary discussion.The treating physician in the hospital will be involved. The general practitioner and community pharmacist will be consulted. An interview and discussion with the patient and/or legal representative by a member of the Pharmacotherapy-team, which will be performed before the patient is discharged from the hospital. A discharge note with the pharmacotherapeutic care plan. This will be sent to the community pharmacist and the general practitioner.<br>* Other names: TMPC;|
| No Intervention: Usual care<br>The comparator in this study is usual care, which refers to the entire spectrum of medication-related interventions by different healthcare providers (physician, pharmacist, nurse etc.) which the patient undergoes during hospital admission. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Drug Related Readmissions in the first 30 days after index hospitalisation | Whether readmission is drug related will be assessed with AT-HARM10 | 30 days after index hospitalisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Drug Related Readmissions at 3 and 12 months after index hospitalisation | Whether readmission is drug related will be assessed with AT-HARM10 | 3 and 12 months after index hospitalisation | 
| Duration of hospitalisation of Drug Related Readmission | Whether readmission is drug related will be assessed with AT-HARM10 | 30 days, 3 months and 12 months after index hospitalisation | 
| Time to first Drug Related Readmission | Whether readmission is drug related will be assessed with AT-HARM10 | 30 days, 3 months and 12 months after index hospitalisation | 
| Number of Emergency Department visits |  | 30 days, 3 months and 12 months after index hospitalisation | 
| Number of all-cause hospital readmissions |  | 30 days, 3 months and 12 months after index hospitalisation | 
| Healthcare costs | In euros, assessed with the iMTA Medical Consumption Questionnaire (iMCQ) | 30 days, 3 months and 12 months after index hospitalisation | 
| Quality of Life measured with EQ-5D-5L | Measured by 5-level EuroQol-5 domains (EQ-5D-5L) questionnaire | 30 days, 3 months and 12 months after index hospitalisation | 
| Cost-effectiveness | In euro per Quality Adjusted Life Year (QALY) gained, by combining costs and quality of life measurements | During the 12 month follow-up | 
| Number of regular medications | Based on number of regular medications in the medication list | At discharge from index hospitalisation and 30 days, 3 months and 12 months after index hospitalisation | 
| Number and type of recommendations in the intervention group | Based on documented recommendations made during TMPC | At discharge from index hospitalisation | 
| Number of implemented recommendations | The number of differences between the pharmacotherapeutic plan composed by the P-team and the participant's current medication list at each time point | 30 days, 3 months and 12 months after index hospitalisation | 
| Activities of Daily Living | Measured with Katz-6 ADL questionnaire | 30 days, 3 months and 12 months after index hospitalisation | 
| Number of patients living independently |  | 30 days, 3 months and 12 months after index hospitalisation | 
| Number of falls |  | 30 days, 3 months and 12 months after index hospitalisation | 
| Mortality |  | 30 days, 3 months and 12 months after index hospitalisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polypharmacy, Medication Review, Aged, Deprescribing