OPTImization of Medication by Transdisciplinary Assessment of Drug Treatment in Elderly Hospitalized Patients

Study Overview
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Brief Summary
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This study is being done to find out if a multi-faceted intervention designed to optimize medication in hospitalized older people with multiple chronic medical conditions exposed to multiple medications can reduce unplanned hospital readmission and emergency department attendance compared to current usual medication management. The study intervention aims to minimize potentially inappropriate medications in a structured way and involves follow up with patients and GPs. Patients will be allocated equally to (i) standard medication management (control arm) or (ii) trained physician-delivered intervention or (iii) clinical pharmacist-delivered intervention.

Detailed Description
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Background: Recurrent hospitalization and unplanned emergency department (ED) attendance resulting from potentially inappropriate medication is an increasingly common phenomenon in older people with multi-morbidity and associated polypharmacy. With a growing older population with multi-morbidity/polypharmacy, there is a pressing need to address the increasing challenge of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) and associated problems that accentuate adverse drug reactions/events and avoidable excess morbidity. There is also an imperative to curb excess healthcare expenditure related to preventable medication-related problems. Objective: To test the clinical and economic impact of a multi-faceted medication optimization definitive intervention on avoidable rehospitalization and unscheduled ED attendance in multi-morbid patients aged ≥ 70 years hospitalized with acute illness.To test the clinical and economic impact of a multi-faceted medication optimization definitive intervention (DI) on avoidable rehospitalization and unscheduled ED attendance in multi-morbid patients aged ≥ 70 years hospitalized with acute illness. Design: A randomized controlled clinical trial is proposed in which it is anticipated to randomize 3 x 463 patients to one of 3 groups: (a) standard pharmaceutical care, or (b) trained physician-implemented DI, or (c) clinical pharmacist-implemented DI. Setting: Acute care environment in 3 large tertiary referral teaching hospitals with similar custom and practice relating to management of older people with acute illness. Participants: Patients aged ≥ 70 years with multi-morbid illness i.e. ≥ 3 chronic medical conditions and associated polypharmacy i.e. ≥ 5 daily prescription medications admitted with acute unselected illness. Intervention: The definitive multi-faceted intervention will consist of the following components:modified structured history of medication (SHiM), Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) screening for PIMs and PPOs using STOPP/START version 3.0, drug-drug interaction screening using Stockley's Drug Interaction Checker, face-to-face consultation with attending hospital physicians to discuss PIMs, PPOs, interactions and other issues, pre-discharge medication review and adjustment, detailed medication adjustment discharge report to patients' general practitioners (GPs), post-discharge follow-up contact with patients' GPs and community pharmacists at 1 week and 1 and 6 months post-discharge. Study Population: OPTIMATE will focus on patients admitted with acute medical or surgical illness through the emergency departments of Cork University Hospital, University Hospital Waterford and Ghent University Hospital. Patients to be screened for enrolment are those admitted primarily under the care of specialist departments other than geriatric medicine. Data Collection: All OPTIMATE trial data will be collected electronically and entered on a bespoke trial proforma. Once verified as fully correct and complete, all individual participant trial data will be stored on a fully secure clinical trial database. Statistical Analysis: Treatment effects for each of the two active intervention arms (versus control) in terms of binary outcomes (e.g. readmission) will be estimated using logistic regression, while Health Related QoL (EQ-5D 5L) will be analyzed using ordinal regression with a logit link function (i.e. a proportional odds model). We will report two models for each outcome: one adjusted for centre and admitting service type; and another further adjusted for centre, age (years), sex, number of comorbidities at baseline, and number of prescribed medications at baseline. Effect estimates will be reported as odds-ratios with 95% confidence intervals and exact p-values. There will be no correction for multiplicity, but we will report results for all outcomes regardless of the result and provide enough information for the reader to make whatever corrections they may consider appropriate. Equivalence tests comparing the two active arms (for each outcome) will be done using a two one-sided tests procedure based on a 90% confidence interval (which equates to a 5% type 1 error rate). All analyses will be conducted on an intention-to-treat basis and will be conducted under the quality system and SOPs of the HRB CRF-C Statistics and Data Analysis Unit. A complete statistical analysis plan (SAP) will be pre-registered on the Open Science Framework prior to patient recruitment database lock. Any necessary deviations from this SAP will be documented and explained in the trial report. There will be only one single trial data analysis at the end of the project. All reporting will be carried out in accordance with CONSORT guidelines for clinical trials.

Official Title
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OPTImization of Medication by Transdisciplinary Assessment of Drug Treatment in Elderly Hospitalized Patients: Application of a Definitive Intervention by Physicians or Clinical Pharmacists

Conditions
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Multimorbidity, Polypharmacy

Intervention / Treatment
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* Other: Definitive multi-faceted intervention consisting of several components
* Other: Sham Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 70years 3 or more chronic conditions. ≥ 5 daily medications pre-admission, all medications taken for at least 4 weeks continuously. ≥ 1 unscheduled hospitalizations in the previous 12 months. Demonstrable frailty (Clinical Frailty Scale 5 to 8) Can speak and understand English (in the two Irish medical centres), and Dutch or French in Ghent University Hospital (Ghent is predominantly Dutch-speaking). Can give informed consent or give witnessed verbal consent. Agrees to follow-up contact post-discharge up to 180 days post-randomization. Agrees to primary researcher contacting the GP and community pharmacist post-discharge. Exclusion Criteria: Terminal illness. Severe dementia and clearly unable to understand the purpose of the trial. Severe communication disorder, making informed consent impossible. Likely to be discharged from hospital within 48 hours of arrival. Intensive Care Unit (ICU) admission. Primary psychiatric presenting illness. Unavailable for post-discharge follow-up for any reason. Non-accidental poisoning. Previous participation in medication optimization trials. Active participation in another clinical trial Current other major psychiatric illness. Infectious illness requiring strict isolation (including COVID-19 infection) blocking access of the primary researcher to the patient for enrolment. End-stage renal, liver or lung disease requiring organ replacement therapy. Admitted under the care of specialists in Geriatric Medicine , Clinical Pharmacology, Palliative Medicine, Clinical Oncology or Haematology. Trial participation refusal.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized controlled clinical trial is proposed in which it is anticipated to randomize 3 x 463 patients to one of 3 groups: (a) standard pharmaceutical care, or (b) trained physician-implemented DI, or (c) clinical pharmacist-implemented DI.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control: standard pharmaceutical care<br>Patients in the control arm (standard pharmaceutical care) will receive a sham intervention in the form of the modified Medication Adherence Rating Scale (MARS) questionnaire | Other: Sham Intervention<br>* Sham intervention in the form of the modified Medication Adherence Rating Scale (MARS) questionnaire in addition to standard care.<br>* Other names: Control;|
| Active Comparator: trained physician-implemented intervention<br>The definitive multi-faceted intervention delivered by a trained physician. | Other: Definitive multi-faceted intervention consisting of several components<br>* The definitive intervention will consist of the following components: structured history of medication (SHiM), Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) screening for PIMs and PPOs, drug-drug and drug-disease interactions screening, face-to-face consultation with attending hospital physicians to discuss PIMs, PPOs, interactions and other issues, pre-discharge medication review and adjustment, detailed medication adjustment discharge report to patients' general practitioners (GPs), post-discharge follow-up contact with patients' GPs and community pharmacists at 1 week, 1 month and 6 months post -discharge. The interventions will be applied by a trained physician or pharmacist.<br>* Other names: Stockley's Drug Interaction Checker;|
| Active Comparator: clinical pharmacist-implemented intervention<br>The definitive multi-faceted intervention delivered by a trained pharmacist. | Other: Definitive multi-faceted intervention consisting of several components<br>* The definitive intervention will consist of the following components: structured history of medication (SHiM), Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) screening for PIMs and PPOs, drug-drug and drug-disease interactions screening, face-to-face consultation with attending hospital physicians to discuss PIMs, PPOs, interactions and other issues, pre-discharge medication review and adjustment, detailed medication adjustment discharge report to patients' general practitioners (GPs), post-discharge follow-up contact with patients' GPs and community pharmacists at 1 week, 1 month and 6 months post -discharge. The interventions will be applied by a trained physician or pharmacist.<br>* Other names: Stockley's Drug Interaction Checker;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unscheduled readmission to hospital. | All-cause re-hospitalization in multi-morbid older people exposed to polypharmacy. Computerized hospital admission records will be inspected. If hospital readmission has occurred dates of admission and discharge will be recorded in the electronic case report form. | At day 30 post-discharge. | 
| Emergency Department attendance. | Unscheduled emergency department attendance at in multi-morbid older people exposed to polypharmacy. Computerized hospital emergency department attendance records will be inspected. The primary researcher will record on the electronic case report form whether there has there been an unscheduled emergency department attendance since the first follow-up post discharge. | At day 30 post-discharge. | 
| Composite endpoint 1 | Composite endpoint of readmission to hospital or emergency department attendance within 30 days of discharge from the index admission. | At day 30 post-discharge. | 
| Unscheduled readmission to hospital. | Unscheduled readmission at 180 days post-discharge in multi-morbid older people exposed to polypharmacy. This will be ascertained during the follow-up interview within 180 (+/-14) days post-discharge. Computerized hospital emergency department attendance records will be inspected. The primary researcher will record on the electronic case report form whether there has there been an unscheduled readmission at 180 days since discharge from the index hospital admission. | At day 180 post-discharge. | 
| Emergency Department attendance. | Unscheduled emergency department attendance at in multi-morbid older people exposed to polypharmacy. This will be ascertained during the follow-up interview within 180 (+/-14) days post-discharge. Computerized hospital emergency department attendance records will be inspected. The primary researcher will record on the electronic case report form whether there has there been an unscheduled emergency department attendance at 180 days since discharge from the index hospital admission. | At day 180 post-discharge. | 
| Composite endpoint 2 | Composite endpoint of readmission to hospital or emergency department attendance within 180 days of discharge from the index admission. | At day 180 post-discharge. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life measured by EuroQol quality of life 5 dimensional 5 level instrument (incorporating pain control) | The EuroQol quality of life 5 dimensional 5 level instrument (EQ5D-5L) is a self-reported quality of life questionnaire comprised of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each of the five dimensions is divided into five levels: level 1 (no problem), level 2 (slight problems), level 3 (moderate problems), level 4 (severe problems) and level 5 (unable to/extreme problems).The results are used to calculate a five digit score that describes the patient's health state. This value is the converted into an index value, on a range between 0 and 1, where 0 represents a state as bad as being dead and 1 represents full health.In addition, the questionnaire has a Visual Analogue Scale question which asks the patient to indicate their overall health on the day of questionnaire completion. This is a 0 -100 scale where 100 represents The best health you can imagine' and 0 'The worst health you can imagine'. | At day 30 post-discharge. | 
| Quality of life measured by EuroQol quality of life 5 dimensional 5 level instrument | The EQ5D-5L is a self-reported quality of life questionnaire comprised of five dimensions. The questionnaire gives a score in the range between 0 and 1, where 0 represents a state as bad as being dead and 1 represents full health.In addition, the questionnaire has a Visual Analogue Scale question which asks the patient to indicate their overall health on the day of questionnaire completion. This is a 0 -100 scale where 100 represents The best health you can imagine' and 0 'The worst health you can imagine'. | At day 180 post-discharge. | 
| All-cause mortality | secondary outcome | At day 30 post-discharge. | 
| All-cause mortality | secondary outcome | At day 180 post-discharge. | 
| Occurrence of first admission to residential care facility for long-term nursing care | secondary outcome | At day 30 post-discharge. | 
| Occurrence of first admission to residential care facility for long-term nursing care | secondary outcome | At day 180 post-discharge. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inappropriate prescribing, multimorbidity, polypharmacy, hospital admission, older people, frail elderly, medication therapy management, STOPP/START