We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

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
ACTRN12621000181808p
Ethics application status
Submitted, not yet approved
Date submitted
4/11/2020
Date registered
22/02/2021
Date last updated
22/02/2021
Date data sharing statement initially provided
22/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The PRESIDE TRIAL
Scientific title
The PRESIDE (PhaRmacogEnomicS In Depression) Trial: a double-blind RCT of
pharmacogenomically-informed prescribing of antidepressants on depression outcomes in
patients with major depressive disorder in primary care.
Secondary ID [1] 302696 0
nil
Universal Trial Number (UTN)
Trial acronym
The PRESIDE TRIAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 319613 0
Condition category
Condition code
Mental Health 317557 317557 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The PRESIDE (PhaRmacogEnomicS In Depression) Trial is a double-blind RCT of pharmacogenomically-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care. In other words, participants who have depressive symptoms will be randomly allocated to one of two groups and neither they, nor their GP, nor the researchers will be aware of which group they are in. One group (intervention) will receive recommendations for which antidepressant drugs may be most effective for them based on how their DNA impacts how they break these drugs down. The other group (control) will receive recommendations for antidepressant drugs based on
current Australian guidelines. All participants, regardless of which group they are in, will decide with their GP which antidepressant, if any, is best for them. This trial addresses significant knowledge gaps related to how clinically useful this type of pharmacogenomic (DNA) test may be in managing patients with major depressive disorder in primary care. It will create evidence about the efficacy, safety, and costeffectiveness of this approach, working with health service delivery partners and research end-users to ensure the findings can be implemented into practice as quickly as possible.
Participants will be recruited (informed consent) from participating Australian General Practices.

For those in the intervention arm, the DNA will be used to generate a recommendation for antidepressant prescribing guided by the participants' pharmacogenomic profile. For those in the control arm, the recommendation for prescribing will be based on the TGA guidelines. Each participant's General Practitioner will be provided with the relevant test report and will be blinded to which group the participant has been allocated into. Neither report will refer to specific genomic variants, only a prescription recommendation. Before recruitment, participants will be informed of the randomised nature of the study and that neither they, nor their GP, nor the study team can allocate them to a particular group. The researcher will ensure they understand as part of the consent process. After 6 months, all participants' GPs, regardless of the participant's arm, will receive their full clinical pharmacogenomic report.

The intervention consists of a pharmacogenomic test with resulting recommendations for which antidepressants may work best for that participant.
The DNA sample will be obtained using the Oragene-DNA buccal kit, which we have used successfully in our previous genotyping studies in primary care. The Sonic Pathology PGx panel will be used for genotyping, with specific focus on two genes: CYP2D6 (alleles *2, *3, *4, *4M, *6, *7, *8, *9, *10, *11, *12, *14A, *14B, *13, *15, *17, *18, *19, *20, *29, *36, *38, *41, *5 (gene deletion), XN (gene duplication) (VeriDose® Core and CYP2D6 CNV Panels) and CYP2C19 (alleles *2, *3, *4, *4B, *5, *6, *7, *8, *17). The allele that each participant carries can predict how they metabolise certain drugs. This is used to create actionable recommendations about antidepressant class and dose, based on Clinical Pharmacogenetics Implementation Consortium (CPIC) and Royal Dutch Pharmacogenetics Working Group (DPWG) international guidelines.(10, 11)
Sonic Genetics has an established pharmacogenomic genotyping and interpretive service in conjunction with Translational Software (https://www.translationalsoftware.com/), which will generate the patient-specific prescribing advice. The recommendations will take into account
concurrent medication use, in particular accounting for CYP2D6 and CYP2C19 inducers and inhibitors, by applying an evidence-based algorithm created by CI Bousman (Sequence2Script).

The GPs of those in both the intervention arm and the control arm will receive a specific prescribing recommendation within 2 weeks of entry into the trial. For those in the intervention arm, this report will be based on the participant’s genotype, predicted metaboliser phenotype, concomitant medication use and the Australian Therapeutic Guidelines. For those in the control arm, this will be based on the Australian Therapeutic Guidelines. To ensure blinding, the report will not refer to the participant’s genotype or phenotype but only provide prescribing recommendations.

All participants will be advised to see their GP to discuss this prescribing report and determine clinical management. They will also be advised to see their GP for review at 2, 4, 8 and 12 weeks after the initial consultation to discuss the prescribing report. This is consistent with current practice for the follow-up of patients with depression in primary care. Patient adherence to antidepressant prescribing using the Medication Adherence Report Scale
(MARS-5) at baseline, 4, 8,12 and 26 weeks. We will use PBS data to calculate the Medication Possession Ratio, an objective measure of adherence which is associated with antidepressant response at the completion of the intervention period.

(10) Hicks JK, et al.. Clin Pharmacol Ther. 2015;98(2):127-34.
(11) Hicks JK, et al. Clin Pharmacol Ther. 2017;102(1):37-44.
Intervention code [1] 318979 0
Diagnosis / Prognosis
Intervention code [2] 318980 0
Early detection / Screening
Comparator / control treatment
All participants' GPs will receive their full pharmacogenomic report after the follow-up period of the trial (6 months). This will be sent to their GPs directly. For those in the intervention arm, this will add to the information about antidepressant recommendations; for those in the control arm, this will include all drugs, including antidepressants based on TGA guided recommendations.
All aspects of the study will be the same for each group, other than the prescribing report, however the reports will look the same. The participants and their GP will not know which group the participant is in.
Control group
Active

Outcomes
Primary outcome [1] 325600 0
The primary outcome will be symptom reduction, defined as change in depressive symptom score measured by the PHQ-9 at 12 weeks from the first GP consultation to discuss the prescribing report.
Timepoint [1] 325600 0
baseline, 4, 8, 12 (primary endpoint), 26 weeks from recruitment.
Secondary outcome [1] 388497 0
Remission (defined as PHQ-9 score <5) and response (defined as >50% decrease from
baseline score on PHQ-9).
Timepoint [1] 388497 0
4, 8, 12 & 26 weeks
Secondary outcome [2] 390871 0
The Antidepressant Side-Effect Checklist (ASEC), a 21-item validated self-reported symptom
checklist previously used in the GENDEP (Genome-Based Therapeutic Drugs for Depression)
study. For each side-effect symptom participants rate severity on a four-point scale (0 –
absent, 3 = severe) and are summed to give a total side-effect score. Outcome is of an exploratory nature.
Timepoint [2] 390871 0
4, 8, 12 & 26 weeks
Secondary outcome [3] 390872 0
The Assessment of Quality of Life (AQoL-4D), a validated measure of quality of life used to
calculate quality-adjusted life years (QALYs) via a utility algorithm.
Timepoint [3] 390872 0
baseline, 12 and 26 weeks
Secondary outcome [4] 390873 0
Health service use will be determined from a non-validated resource use questionnaire (RUQ) supplemented with administrative data from the Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data, with specific participant consent. Hospitalisations/emergency department data will be accessed via the Centre for Victorian Data Linkage.
Timepoint [4] 390873 0
Baseline, 12 & 26 weeks
Secondary outcome [5] 390874 0
Number of medication changes, obtained from GP medical record audit and PBS data.
Timepoint [5] 390874 0
26 weeks / completion of intervention period
Secondary outcome [6] 390875 0
Concordance of GP prescribing with recommendations in the prescribing report will be captured through GP medical
record audit and PBS data.
Timepoint [6] 390875 0
26 weeks / at completion of intervention period
Secondary outcome [7] 390876 0
Patient adherence to antidepressant prescribing using the Medication Adherence Report Scale (MARS-5). This 5-item validated self-reported scale has been used widely to study
medication adherence for a range of chronic and mental health conditions. We will use
PBS data to calculate the Medication Possession Ratio, an objective measure of adherence
which is associated with antidepressant response.
Timepoint [7] 390876 0
baseline, 4, 8, 12 & 26 weeks
Secondary outcome [8] 390877 0
FIBSER (frequency, intensity, burden of side effect rating) - medication side effect , using validated questionnaire. Outcome is of an exploratory nature.
Timepoint [8] 390877 0
baseline, 4, 8, 12 and 26 weeks

Eligibility
Key inclusion criteria
• Eligible participants for the trial are aged between 18 and 65 years old
• Participants able to read and write English and competent to give informed consent
• Participants who are contactable over the next 6 months for the study follow-up
• Symptoms of depression - identified in the PHQ-9 initial screening questionnaire (iPad/phone delivery).
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Ineligible
• pregnant
• currently taking antipsychotic medication
• significant suicidal risk
• dementia

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is done after a participant has been recruited and is sent to the holder of the allocation schedule who is "off-site" at the central study administration site. The allocation sequence is computer-generated, to ensure allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
sequentially stratified by current antidepressant use and general practice,using a biased-coin algorithm that will be embedded within the online database.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
672 primary care patient participants across 8-10 GP practices.

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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 307131 0
Government body
Name [1] 307131 0
The Medical Research Future Fund (MRFF), Department of Health
Address [1] 307131 0
The Medical Research Future Fund (MRFF)
Department of Health
GPO Box 9848
Canberra ACT 2601
Country [1] 307131 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Department of General Practice
Faculty of Medicine, Dentistry and Health Sciences
Level 10, Victorian Comprehensive Cancer Centre,
305 Grattan Street, Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 307710 0
None
Name [1] 307710 0
Address [1] 307710 0
Country [1] 307710 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307243 0
The University of Melbourne Human Research Ethics Committees (HREC)
Ethics committee address [1] 307243 0
Human Research Ethics Committees (HREC)
The University of Melbourne
Carlton, 3010 VIC
Ethics committee country [1] 307243 0
Australia
Date submitted for ethics approval [1] 307243 0
10/12/2020
Approval date [1] 307243 0
Ethics approval number [1] 307243 0

Summary
Brief summary
The PRESIDE Trial is a double-blind RCT of pharmacogenomically-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care. Participants who have depressive symptoms will be randomly allocated to one of two groups and neither they, nor their GP, nor the researchers will be aware of which group they are in. One group will receive recommendations for which antidepressant drugs may be most effective for them based on how their DNA impacts how they break these drugs down. The other group will receive recommendations for antidepressant drugs based on current Australian guidelines. All participants, regardless of which group they are in, will decide with their GP which antidepressant, if any, is best for them. This trial addresses significant knowledge gaps related to how clinically useful this type of pharmacogenomic (DNA) test may be in managing patients with major depressive disorder in primary care. It will create evidence about the efficacy, safety, and cost-effectiveness of this approach, working with health service delivery partners and research end-users to ensure the findings can be implemented into practice as quickly as possible.
Trial website
nill
Trial related presentations / publications
nil
Public notes
nil

Contacts
Principal investigator
Name 106538 0
Prof Jon Emery
Address 106538 0
Department of General Practice, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne
Level 10, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne VIC 3000

Country 106538 0
Australia
Phone 106538 0
+61385597044
Fax 106538 0
Email 106538 0
jon.emery@unimelb.edu.au
Contact person for public queries
Name 106539 0
Prof Jon Emery
Address 106539 0
Department of General Practice, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne
Level 10, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne VIC 3000

Country 106539 0
Australia
Phone 106539 0
+61385597044
Fax 106539 0
Email 106539 0
jon.emery@unimelb.edu.au
Contact person for scientific queries
Name 106540 0
Prof Jon Emery
Address 106540 0
Department of General Practice, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne
Level 10, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne VIC 3000

Country 106540 0
Australia
Phone 106540 0
+61385597044
Fax 106540 0
Email 106540 0
jon.emery@unimelb.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?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 10109 0
Study protocol
Citation [1] 10109 0
Link [1] 10109 0
Email [1] 10109 0
sibel.saya@unimelb.edu.au
Other [1] 10109 0
Attachment [1] 10109 0
Type [2] 10110 0
Ethical approval
Citation [2] 10110 0
Link [2] 10110 0
Email [2] 10110 0
sibel.saya@unimelb.edu.au
Other [2] 10110 0
Attachment [2] 10110 0
Type [3] 10112 0
Informed consent form
Citation [3] 10112 0
Link [3] 10112 0
Email [3] 10112 0
sibel.saya@unimelb.edu.au
Other [3] 10112 0
Attachment [3] 10112 0
Summary results
No Results