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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Polypharmacy; Medication Review
• Intervention / Treatment: Other: Transitional Multidisciplinary Pharmacotherapeutic Care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 2576
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • Universitair Medisch Centrum Groningen
  • Utrecht, Netherlands
    • Diakonessenhuis
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Radboudumc
    • Nijmegen, Gelderland, Netherlands
      • Canisius Wilhelmina Ziekenhuis
  • Noord Brabant
    • Breda, Noord Brabant, Netherlands
      • Amphia ziekenhuis
    • Eindhoven, Noord Brabant, Netherlands
      • Catharina Ziekenhuis
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands
      • Amsterdam UMC - location VUMC
    • Amsterdam, Noord-Holland, Netherlands
      • Amsterdam UMC- location AMC
    • Zaandam, Noord-Holland, Netherlands
      • Zaans Medisch Centrum
  • Overijssel
    • Almelo, Overijssel, Netherlands
      • Ziekenhuisgroep Twente
    • Deventer, Overijssel, Netherlands
      • Deventer Ziekenhuis
  • Utrecht
    • Amersfoort, Utrecht, Netherlands
      • Meander Medisch Centrum Amersfoort
  • Zuid Holland
    • Rotterdam, Zuid Holland, Netherlands
      • Erasmus Medisch Centrum Rotterdam
  • Zuid-Holland
    • Den Haag, Zuid-Holland, Netherlands
      • Haga ziekenhuis
    • Leiden, Zuid-Holland, Netherlands
      • Leiden Universitair Medisch Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transitional Multidisciplinary Pharmacotherapeutic Care (TMPC); 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; 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.; Other Names: TMPC
No Intervention: Usual care; 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?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: University Medical Center Groningen; UMC Utrecht; Erasmus Medical Center; Catharina Ziekenhuis Eindhoven; Amsterdam UMC, location VUmc; Leiden University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development; Zaans Medisch Centrum; Diakonessenhuis, Utrecht; Deventer Ziekenhuis; Ziekenhuisgroep Twente; Meander Medisch Centrum; Zorgevaluatie Nederland; HagaZiekenhuis; Amsterdam UMC, location AMC; Amphia ziekenhuis; Canisius Wilhelmina Ziekenhuis (CWZ)
• Investigators: Principal Investigator: Kees Kramers, Prof. Dr., Radboud University Medical Center

Publications and helpful links

Helpful Links

• LIMONCELLO website in collaboration with "Zorgevaluatie Nederland"

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2023
• Primary Completion (Actual): April 1, 2025
• Study Completion (Estimated): January 17, 2026

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Polypharmacy; Aged; Deprescribing; Medication Review
• Other Study ID Numbers: NL82393.091.22; 10330032010002 (Other Grant/Funding Number: ZonMw)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data will be shared in a repository, published under restricted access.
• IPD Sharing Time Frame: All collected data will be stored for 15 years
• IPD Sharing Access Criteria: It will be shared in a repository. The data will be published under restricted access. Requests for access will be checked, by a data access committee (DAC) formed by the consortium.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No