The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000766213
Ethics application status
Approved
Date submitted
2/05/2018
Date registered
7/05/2018
Date last updated
21/11/2018
Date data sharing statement initially provided
21/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacist service to reduce adverse events in residential aged care facilities
Scientific title
Pharmacist-led service to reduce medicine-induced deterioration and adverse reactions in older people living in residential aged care facilities
Secondary ID [1] 293583 0
None
Universal Trial Number (UTN)
U1111-1213-2859
Trial acronym
ReMInDAR Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polypharmacy 307695 0
Condition category
Condition code
Public Health 306759 306759 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The ‘intervention’ is a 12-month pharmacist led assessment of signs and symptoms of medicine-induced deterioration and adverse medicine events. The assessment will occur subsequent to a change in the person’s medicine regimen, with persons eligible for a maximum of one assessment per month.

In implementing the service, the pharmacist will use a suite of validated tools (Montreal Cognitive Assessment MoCA, activity tracker and dynamometer) to assist in the detection of signs and symptoms of medicine-induced deterioration. The validated tools will encompass assessments to monitor changes in cognition, change in 24-hour movement behavior, including sleep, as well as grip strength. The validated tools will be administered by the pharmacists with each resident required to complete the tools only where there is a change in the medication regime. In addition, pharmacists will assess the potential for adverse medicine events via review of the resident care assessment record and through patient or carer reported changes in health since the medicine regimen was changed.

A risk matrix will be developed specifically for this study. The risk matrix will be employed to assist pharmacists to determine the likelihood that medicine-induced deterioration is present and whether the deterioration is likely to lead to harm. Medicine-induced deterioration will be defined using the minimum clinically significant difference known for the validated tool. Where changes are greater than 20% (relative) above the minimum clinically significant difference, the potential for harms will be considered high.

Where medicine-induced deterioration is present and there is high risk of harm, a case conference with the resident's general practitioner will be scheduled. Where warranted, a medicine action plan will be developed and subsequently implemented by the pharmacist. The medicine action plan will include plans to continue, withhold, cease or change the medicine to another medicine with similar mechanism of action but with reduced risk of harm.
Where the medicine action plan results in changes to the medication regimen, the pharmacist will reassess the resident to determine if medicine induced deterioration or adverse events have resolved. Since each participant is eligible for a maximum of one pharmacist service per month, and assessment would occur only subsequent to change in medicine, we anticipate that participants will be assessed a maximum of 12 times. This is based on the assumptions that:
- A participant has 6 medicine change per year which results in high risk of harm;
- All six action plans results in changes in medication regime, therefore requiring reassessment of the participant.
To ensure adherence and fidelity to the trial, a study coordinator will oversee the scheduled monthly pharmacist service.

Intervention code [1] 301086 0
Prevention
Comparator / control treatment
The comparator cohort will receive usual care provided under the existing pharmacist
service. Usual care refers to the annual or biennial Residential Medication Management Reviews (RMMR) provided to residents in approved Australian Government funded aged care facilities,
These services will still be available to the intervention and control group during this time.
Control group
Active

Outcomes
Primary outcome [1] 305747 0
Change in frailty level as assessed using the frailty index
Timepoint [1] 305747 0
Baseline, 6-months post-baseline, 12 months post-baseline (primary endpoint)
Secondary outcome [1] 346349 0
Change in cognitive function as measures using the Montreal Cognitive Assessment (MoCA)
Timepoint [1] 346349 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [2] 346350 0
Change in 24 hour movement behaviour (sleep time) as measured using GENEActiv activity tracker
Timepoint [2] 346350 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [3] 346351 0
Grip strength (dynamometer)
Timepoint [3] 346351 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [4] 346352 0
Change in weight as measured using a digital scale
Timepoint [4] 346352 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [5] 346353 0
Change in percentage of robust, pre-frail and frail individuals as measured using the frailty phenotype. The frailty phenotype comprises five criteria: unintentional weight loss, low grip strength, self-rated exhaustion, low walking time and low physical activity. In the frailty phenotype, individuals are classified as frail if they meet three or more of the five criteria, and pre-fail if they have one or two attributes. Individuals who meet none of the criteria are classified as robust.
Timepoint [5] 346353 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [6] 346354 0
Rate of adverse medicine events (such as falls, fractures, delirium, faecal impaction) via a review of the Resident Care Assessment Record
Timepoint [6] 346354 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [7] 346355 0
Change in quality of life as measured using EQ-5D
Timepoint [7] 346355 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [8] 346356 0
Changes in health resource use will be collected from resident care record. Data will be collected on intervention-associated resource use (pharmacist, doctor, nursing and care staff time, changes in medication and non-medication management) and resource use associated with any adverse events.
Timepoint [8] 346356 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [9] 346434 0
Change in 24 hour movement behaviour (total activity time) as measured using GENEActiv activity tracker
Timepoint [9] 346434 0
Baseline, 6-months post-baseline, 12 months post-baseline
Secondary outcome [10] 346435 0
Change in 24 hour movement behaviour (light, moderate and vigorous intensity activity) as measured using GENEActiv activity tracker
Timepoint [10] 346435 0
Baseline, 6-months post-baseline, 12 months post-baseline

Eligibility
Key inclusion criteria
1) Receive services from an eligible aged-care facility;
2) Use four or more medicines at the time of recruitment or on more than one
medicine one of which has anticholinergic or sedative properties.
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Persons with significant existing frailty burden, defined as a score of 0.40 or
above using the Frailty Index;
2) Persons with moderate or severe dementia;
3) Persons receiving palliative care;
4) Persons receiving respite care;
5) Persons participating in another research project

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will involve contacting the holder of the allocation schedule at a central administration site
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A total sample size of 506 will provide 80% power to detect a difference in the change in frailty scores over 12 months of half a deficit. A total sample size of 676 will provide 90% power to detect a difference of ½ a deficit over 12 months.
The primary efficacy endpoint is the difference (d) in mean frailty score after 12 months post randomisation. An individual’s frailty score, as measured by the Frailty Index at follow-up (6 and 12 months) will be compared to their baseline Frailty score. The individual’s change score will then be compared between the intervention and comparator groups. Since frailty measurements will be measured at multiple times (baseline, 6 months and 12 months) the changes over time within-patients and between the intervention and comparator groups will be analysed using a multi-level modeling (MLM) framework. This framework effectively models the correlation between an individual’s frailty overtime and the clustering of patients within nursing homes and pharmacists. This approach will also allow for variability in the timing of measurements.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,TAS

Funding & Sponsors
Funding source category [1] 298199 0
Government body
Name [1] 298199 0
Australian Government Department of Health Pharmacy Trial Program
Address [1] 298199 0
GPO Box 9848,
Canberra ACT 2601
Country [1] 298199 0
Australia
Primary sponsor type
Government body
Name
Australian Government Department of Health Pharmacy Trial Program
Address
GPO Box 9848,
Canberra ACT 2601
Country
Australia
Secondary sponsor category [1] 297298 0
None
Name [1] 297298 0
Address [1] 297298 0
Country [1] 297298 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299209 0
University of South Australia Human Research Ethics Committee
Ethics committee address [1] 299209 0
GPO Box 2471
Adelaide, South Australia 5001
Ethics committee country [1] 299209 0
Australia
Date submitted for ethics approval [1] 299209 0
30/03/2017
Approval date [1] 299209 0
15/05/2017
Ethics approval number [1] 299209 0
0000036440
Ethics committee name [2] 300287 0
Tasmania Health and Medical Human Research Ethics Committee
Ethics committee address [2] 300287 0
Office of Research Services,
University of Tasmania,
Private Bag 1,
Hobart, TAS, 7001
Ethics committee country [2] 300287 0
Australia
Date submitted for ethics approval [2] 300287 0
28/11/2017
Approval date [2] 300287 0
15/02/2018
Ethics approval number [2] 300287 0
H0017022

Summary
Brief summary
This randomised controlled trial will assess a pharmacist led intervention to reduce
medicine induced deterioration and adverse reactions. Medicine induced deterioration encompasses the spectrum of side effects that are frequently not recognised as medication related but are misattributed as geriatric syndromes, frailty or “changes due to aging”.
The aim of the service is to enable early identification of signs and symptoms of medicine-induced deterioration so that worsening frailty and subsequent adverse events, such as injurious falls, fractures and delirium are prevented. In implementing the service, the pharmacist will use a suite of validated tools to assist in the detection of signs and symptoms of medicine-induced deterioration. The validated tools will encompass assessments to monitor changes in cognition, change in 24-hour movement behavior, including sleep, as well as grip strength. In addition, pharmacists will assess the potential for adverse medicine events via review of the resident care assessment record and through patient or carer reported changes in health since the medicine regimen was changed.
The pharmacist service will be compared with usual care. The trial, involving 676 patients will take place in aged-care facilities in South Australia and Tasmania.
The expected clinical outcome is a reduction in medication-induced deterioration, as measured by change in frailty score.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79662 0
Prof Libby Roughead
Address 79662 0
Quality Use of Medicines and Pharmacy Research Centre,
School of Pharmacy and Medical Sciences
University of South Australia,
Frome Road,
Adelaide SA 5001
GPO Box 2471
Country 79662 0
Australia
Phone 79662 0
+61883021238
Fax 79662 0
Email 79662 0
Libby.Roughead@unisa.edu.au
Contact person for public queries
Name 79663 0
Dr Rebecca Bilton
Address 79663 0
Quality Use of Medicines and Pharmacy Research Centre,
School of Pharmacy and Medical Sciences
University of South Australia,
Frome Road,
Adelaide SA 5001
GPO Box 2471
Country 79663 0
Australia
Phone 79663 0
+61883022812
Fax 79663 0
Email 79663 0
rebecca.bilton@unisa.edu.au
Contact person for scientific queries
Name 79664 0
Dr Renly Lim
Address 79664 0
Quality Use of Medicines and Pharmacy Research Centre,
School of Pharmacy and Medical Sciences
University of South Australia,
Frome Road,
Adelaide SA 5001
GPO Box 2471
Country 79664 0
Australia
Phone 79664 0
+61883022307
Fax 79664 0
Email 79664 0
renly.lim@unisa.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Attachments/websites
Type [1] 379 0
Study protocol
URL/details/comments [1] 379 0
Attachment [1] 379 0
Summary results
Not applicable