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Trial registered on ANZCTR


Registration number
ACTRN12619000729123
Ethics application status
Approved
Date submitted
30/04/2019
Date registered
14/05/2019
Date last updated
15/11/2019
Date data sharing statement initially provided
14/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Preventing Adverse Drug Reactions in Older Australians
Scientific title
Prevention of Adverse Drug Reactions in Older Patients After Discharge Using a Pharmacist Intervention: A Randomized Controlled Trial
Secondary ID [1] 298104 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PADR-AD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adverse drug reactions 312620 0
Elderly 312658 0
Condition category
Condition code
Public Health 311128 311128 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We developed and validated a risk score (the PADR-EC score) for ADR-related hospitalization in older patients. We will conduct an open-label randomized controlled trial to investigate the effectiveness of an intervention to reduce the risk of ADRs during and following hospitalization compared to control. Patients 65 years or older who are admitted under the care of a medical team at the Royal Hobart Hospital will be approached to provide their consent. Their nominated general practice and community pharmacy will also be provided with relevant information to enable follow up. All patients will undertake a comprehensive interview to establish their baseline risk of ADRs using an ADR risk score, and will then be randomized to the intervention or control group using a central randomization service. For intervention patients, in addition to usual care, a clinical pharmacist researcher will prepare a comprehensive ADR risk assessment and medication management plan based on the level of risk (low/moderate/high), which will be shared with the clinical team during the hospitalization to inform in-hospital care. The ADR risk assessment is done using the PADR-EC score. The PADR-EC score was developed based on ADR admissions to the hospital to identify people at high risk of ADRs and uses the risk factors of recent medication changes, inappropriate anticholinergic drugs, dementia, renal impairment, and multiple antihypertensives to categorize the risk of ADRs. The management plan includes considering the following factors that impact on the PADR-EC score and ADR risk
• Recent medication changes
• Renal impairment defined as eGFR less than 60mL/min
• Dementia – is there a documented diagnosis in the notes?
• Number of antihypertensives
• Anticholinergic medications
• Any other clinically relevant drug-related problems that could lead to ADRs
This will also form a part of the discharge plan, which will be communicated to each intervention patient’s nominated GP and community pharmacy.
The best possible medication history is collected from the patients and their relatives and/or
caregivers, their general practitioner, and/or community pharmacy. The patients’ previous
admission/discharge details are also stored as an electronic patient file or digital medical record, which could also be accessed during the study for any missing information.
Intervention code [1] 314331 0
Prevention
Comparator / control treatment
The control group will receive usual care during the hospital admission and at the point of discharge, with GPs receiving the standard discharge summary. The usual care is defined as the routine care received by patients for prevention or treatment of diseases.
Control group
Active

Outcomes
Primary outcome [1] 319897 0
The composite primary outcome will be the incidence rate of moderate-severe adverse drug reactions (ADRs) (defined as those requiring hospital treatment, change in therapy or specific treatment). The ADR is assessed based on patient-reported ADRs. If an ADR is reported by the participant, the participant’s GP will be contacted by fax or phone to confirm the reported ADR. The examples of ADRs are hypotension, bleeding, renal impairment, etc.
An ADR will be suspected if the patient’s symptoms/signs and or laboratory abnormalities are consistent with the known adverse effect profile of the drug (if, after appropriate investigations, other causes of symptoms were excluded). All patients initially categorized as having an ADR whether in the hospital or after by the clinical pharmacist researcher will be independently and blindly assessed by another two investigators. The causality, severity, and preventability will be determined using the Naranjo ADR Probability Scale, the Hartwig ADR Severity Scale, and a modified Schumock and Thornton Preventability Scale.
Timepoint [1] 319897 0
The patient reported ADRs are collected 12-months after discharge post commencement of the intervention. During the patient follow-up phone calls, the information will be obtained about any patient-reported ADRs experienced in the interim time. If an ADR is reported by the participant, the participant’s GP will be contacted by fax or phone to confirm the reported ADR at the end of the 12-month follow-up.
Secondary outcome [1] 369817 0
The rate of adverse drug reaction-related hospitalization will be a secondary outcome.
The best possible medication history is collected from the patients and their relatives and/or caregivers, their general practitioner (GP), and/or community pharmacy. The patients’ previous admission/discharge details are also stored as an electronic patient file or digital medical record, which could also be accessed during the study for any missing information.
All patients initially categorized as having an ADR whether in the hospital or after by the clinical pharmacist researcher will be independently and blindly assessed by another two investigators. The causality, severity, and preventability will be determined using the Naranjo ADR Probability Scale, the Hartwig ADR Severity Scale, and a modified Schumock and Thornton Preventability Scale.

Timepoint [1] 369817 0
12-months after discharge post commencement of intervention.

Eligibility
Key inclusion criteria
Patients aged 65 years and older with an unplanned overnight admission to a medical ward in the Royal Hobart Hospital, Tasmania.
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients unwilling to consent to the study
Patients unable to consent to the study with a consenting authority not present at the hospital
Patients unable to be interviewed due to health reasons, with a consenting authority not present at the hospital
Patients unavailable for follow-up
Patients residing in, or being discharged to a nursing home
Patients being transferred to a palliative care unit
Medical notes not available
Patients already enrolled in a post-discharge intervention

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 is concealed by doing a Central Randomization service (Griffith Randomisation Service).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (Griffith randomization service -automated 24-hour randomization service using via a web portal). Researchers within the study team login, then enter key information. Allocation occurs instantly. Confirmation emails are generated automatically and sent to relevant personnel in the study team.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Based on previous recruitment experience for a similar study, we anticipate approaching approximately 1800 patients 65 years and older and recruiting 1200 participants within 18 months. Allowing for drop-outs, this should leave patients randomized through Griffith Randomisation Service into control (n = 500) or intervention (n = 500) groups. A sample size of 435 patients per group is required to detect a 5% difference in the primary outcome (power of 80% and p<0.05).
Baseline characteristics will be compared using appropriate descriptive statistics. Comparisons for similarity will be made using appropriate statistical tests. The primary outcome of cumulative ADR incidence at 12 months will be compared between control and intervention groups on the presence of any ADR per patient basis using appropriate statistical tests.
The secondary outcome of ADR-related hospitalization will be compared between control and intervention groups and assessed using appropriate statistical tests. The ADR rate will be expressed as the ADR incidence /100 patient-years of follow-up.

Recruitment
Recruitment status
Not yet 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)
TAS
Recruitment hospital [1] 13673 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 26356 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 302634 0
Charities/Societies/Foundations
Name [1] 302634 0
The HCF Research Foundation
Address [1] 302634 0
Level 7, 403 George Street Sydney NSW 2000
Country [1] 302634 0
Australia
Primary sponsor type
Individual
Name
Luke Bereznicki
Address
Professor of Pharmacy
Pharmacy, School of Medicine
College of Health and Medicine
University of Tasmania
Pharmacy Building
Sandy Bay TAS 7001
Country
Australia
Secondary sponsor category [1] 302546 0
University
Name [1] 302546 0
University of Tasmania
Address [1] 302546 0
University of Tasmania,
Private Bag 1
Hobart TAS 7001
Country [1] 302546 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303260 0
Tasmanian Health and Medical Human Research Ethics Committee
Ethics committee address [1] 303260 0
University of Tasmania
Building 1, 1st Floor, 301 Sandy Bay Road
Hobart TAS 7001
Ethics committee country [1] 303260 0
Australia
Date submitted for ethics approval [1] 303260 0
13/06/2019
Approval date [1] 303260 0
23/09/2019
Ethics approval number [1] 303260 0
H0018196

Summary
Brief summary
In Australians 65 years and older, 19% of hospital admissions to medical wards are associated with serious side-effects from medications. Almost 90% of these admissions are preventable through safer use of medicines. The research team have developed a novel method of identifying people at risk of these problems. In this study hospital pharmacists will assess the risk of serious side-effects in people admitted to hospital and make recommendations to reduce this risk to hospital staff, general practitioners and pharmacists. We will test whether this strategy reduces the risk of these events compared to standard care in the 12 months following hospital discharge. We hypothesize that ADR risk assessment on admission to hospital and communication of this risk, with recommendations that target the specific risk factors identified, will reduce the incidence of ADRs occurring during admission and in the 12-months post-discharge.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93046 0
Prof Luke Bereznicki
Address 93046 0
Professor of Pharmacy
Pharmacy | School of Medicine
College of Health and Medicine
University of Tasmania
Pharmacy Building
Sandy Bay TAS 7001
Country 93046 0
Australia
Phone 93046 0
+61 3 6226 2195
Fax 93046 0
Email 93046 0
luke.bereznicki@utas.edu.au
Contact person for public queries
Name 93047 0
Dr Nibu Parameswaran Nair
Address 93047 0
Postdoctoral Research Fellow in Medication Safety
Pharmacy | School of Medicine
College of Health and Medicine
University of Tasmania
Private Bag 26, Hobart TAS 7001
Country 93047 0
Australia
Phone 93047 0
+61 3 6226 2195
Fax 93047 0
Email 93047 0
nnair@utas.edu.au
Contact person for scientific queries
Name 93048 0
Prof Luke Bereznicki
Address 93048 0
Professor of Pharmacy
Pharmacy | School of Medicine
College of Health and Medicine
University of Tasmania
Pharmacy Building
Sandy Bay TAS 7001
Country 93048 0
Australia
Phone 93048 0
+61 3 6226 2195
Fax 93048 0
Email 93048 0
luke.bereznicki@utas.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results