OPtimising thERapy to Prevent Avoidable Hospital Admissions in the Multimorbid Older People

Study Overview
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Brief Summary
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The objective of this Randomised Controlled Trial (RCT) is to evaluate whether the Systematic Tool to Reduce Inappropriate Prescribing (STRIP) including STRIP assistant (STRIPA) implemented by an appropriately qualified team will lead to an improvement in clinical and economic outcomes among patients aged 70 years and more with multimorbidity and polypharmacy.

Detailed Description
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Background: Drug-related morbidity and mortality is an increasing problem in European healthcare systems. Multimorbidity, polypharmacy and old age are important risk factors for drug-related hospital admissions (DRA). The reported incidence of DRAs in the elderly may be as high as 30% of all acute cases, and about half of DRAs are likely to be preventable. They are mainly related to prescribing problems and non-compliance with drug regimens. A significant proportion of healthcare costs are spent on unnecessary interventions and inappropriate medications. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) is a structured method to perform a medication review to optimise pharmacotherapy. Design: European multi-centre, cluster randomised, controlled trial of people aged 70 years or older, with multimorbidity and polypharmacy, being on an ambulatory visit or on a hospital stay in one of the four participating centres in Ireland, Belgium, Switzerland and the Netherlands. A cluster is defined around a treating physician, i.e. the treating physician is randomised and defines the allocation of his patients. Clusters of patients will be randomised to the intervention arm receiving STRIP for optimising therapy or to the control arm undergoing usual clinical care. The patients of physicians who are allocated to the intervention group will undergo a systematic drug review and pharmacotherapy optimisation by a physician and a pharmacist using STRIP, including the STRIPA software. That provides the research team with a recommendation of changes in the patient's medication. Based on STRIPA recommendation and agreement on changes to the patients' pharmacotherapy between the team of the research physician and pharmacist and the prescribing physician, will the patient receive structured counselling about his/her medication; general practitioners will receive a report. Patients will be further followed for 1 year with follow-up phone calls after 2, 6 and 12 months. For the purpose of this trial, all hospitalisations during follow-up of participants will be adjudicated to assess their relationship to adverse drug events. Objectives: The primary objective is to assess the effect of a structured medication review and pharmacotherapy optimisation using the STRIP on drug-related hospitalisations (DRA) caused by over-, mis-, and underuse or over-, mis-, and underprescribing of medications. Secondary objectives will be to assess the impact of pharmacotherapy optimisation on falls, quality of life, polypharmacy, medication changes, activities of daily living, and mortality. Statistical considerations: 80 clusters with a cluster size ranging from 12 to 38 participants will be included. Therefore, 2000 patients, 1000 patients in each arm, will be recruited over 18 months. The trial will have 80% power with this sample size. The primary analysis will be an intention-to-treat (ITT) analysis, whereby all randomised patients will be included in the group they were allocated to. The primary outcome of drug-related admission will be analysed using a random-effects competing risk proportional hazards model that accounts for the competing risk of death and for clustering of data within centre and prescribing physician. Overall survival will be analysed using a random-effects Cox proportional hazards model that accounts for clustering of data within centre and prescribing physician. The analysis of falls will also take into account the competing risk of death. Continuous outcomes will be analysed by random-effects linear regression. All effect measures will be accompanied by 95% confidence intervals and all p-values will be two-sided.

Official Title
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OPERAM: OPtimising thERapy to Prevent Avoidable Hospital Admissions in the Multimorbid Older People: a Cluster Randomised Controlled Trial

Conditions
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3 or More Chronic Conditions for 6 Months or Longer, 5 or More Regular Drugs

Intervention / Treatment
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* Other: STRIP intervention
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: People 70 years of age or older Multimorbidity: 3 or more coexistent chronic conditions defined by 3 distinct International Classification of Diseases (ICD-10) codes with an estimated duration of 6 months or more or based on a clinical decision Polypharmacy i.e. five or more different regular drugs (defined as authorised medications with registration numbers) for more than 30 days. In inpatient: Estimated minimal length of stay within the cluster is sufficient to apply the intervention If outpatient: prescribing physician has GP function and has a planned appointment to conduct intervention Exclusion Criteria: Inability to provide informed consent or to obtain informed consent from a proxy for patients with cognitive impairment Direct admission to palliative care (< 24h after admission) Has passed or will pass a systematic structured drug review during this hospitalisation or within the last two months

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STRIP intervention<br>The intervention will take place during the initial hospital admission (Index Hospitalisation) or an equivalent situation for outpatients. STRIP is a structured method to perform pharmacotherapy optimisation. The STRIP-intervention consists of 9 steps. | Other: STRIP intervention<br>* The STRIP intervention consists of 9 steps: structured history taking of medication recording medication and diagnoses in STRIPA structured drug review based on the STRIPA with the integrated Screening Tool of Older Person's Prescriptions (STOPP)/ Screening Tool to Alert Doctors to the Right Treatment (START) criteria communication and discussion of the structured drug review with prescribing physician with possible adaptation of the recommendation shared decision-making with the patient with possible adaptation of the recommendation optional revision based on new accumulating data during hospitalisation (e.g. new diagnoses, adverse drug reactions) generation of general practioner (GP) report delivery of the report to the patient and to the GP (optional additional direct communication) follow-up<br>* Other names: Systematic drug review;|
| Sham Comparator: Control<br>Participants in the control group will receive medication review by the prescribing physicians in accordance with usual care. If an extended drug review is in place in a ward/specialty corresponding characteristics are collected on cluster level. | Other: Control<br>* Standard care in the department where the trial is conducted. To keep the patients and the blinded team members blinded one questionnaire will be conducted by the intervention team in both arms. This is considered a SHAM intervention.<br>* Other names: Standard care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients with confirmed DRA after discharge from the index hospitalisation | The primary outcome is defined as the first confirmed DRA after discharge from the index hospitalisation within a period of 12 months. Confirmation of a drug-related hospital admission will be assessed by an independent and blinded adjudication committee (per site). Prolongation of the index hospitalisation and prolongation of any following hospitalisations will not be adjudicated for drug-relatedness. Adjudication is done according to specific guidelines. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of survivors | Including causes of death | 12 months | 
| Number of cancer deaths | As subgroup of all deaths this is considered a negative control outcome. | 12 months | 
| Number of patients with hospitalisations | Detected during the follow-up phone calls | 12 months | 
| Number of patients with falls | Detected during the follow-up phone calls | 12 months | 
| Patients' degree of poly-pharmacy | Degree of polypharmacy, defined as the number of regular long-term medications | 12 months | 
| Patients' quality of life | Quality of life as measured by the visual analogue scale of the European Quality of Life-5 Dimensions instrument (EQ-5D) | 12 months | 
| Patients' level of pain/discomfort | Item form EQ-5D questionnaire | 12 months | 
| Patients' basic activities of daily living | Measured by questionnaire Barthel Index Basic Activities of Daily Living (ADL) | 12 months | 
| Patients' drug compliance | Measured by the Morisky Medication Adherence Questionnaire (MMAS-8) | 12 months | 
| Number of clinically significant drug-drug interactions | Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected | 2 months | 
| Number of drug overuse | Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected | 2 months | 
| Number of drug underuse | Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected | 2 months | 
| Number of potentially inappropriate medications | Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected | 2 months | 
| Number of patients with a serious adverse event |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Utilization Review, Older people