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Trial registered on ANZCTR


Registration number
ACTRN12622000444785
Ethics application status
Approved
Date submitted
8/03/2022
Date registered
21/03/2022
Date last updated
15/09/2023
Date data sharing statement initially provided
21/03/2022
Date results information initially provided
15/09/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Micro-dosing with buprenorphine to transfer from methadone to buprenorphine – a prospective non-randomised open label clinical trial
Scientific title
Micro-dosing with buprenorphine to transfer from methadone to buprenorphine in adults with opioid dependence – a prospective non-randomised open label clinical trial
Secondary ID [1] 306631 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid dependence 325550 0
Condition category
Condition code
Mental Health 322923 322923 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transfer of patients from methadone to buprenorphine using micro-dosing technique.
Dosing regimen (where X is current dose of methadone):
Day 1: Methadone Xmg daily per oral liquid; Buprenorphine 0.2mg twice a day sublingual tablet
Day 2: Methadone Xmg daily per oral liquid; Buprenorphine 0.4mg twice a day sublingual tablet
Day 3: Methadone Xmg daily per oral liquid; Buprenorphine 2mg daily sublingual tablet
Day 4: Methadone Xmg daily per oral liquid; Buprenorphine 4mg daily sublingual tablet
Day 5: Methadone Xmg daily per oral liquid; Buprenorphine 8mg daily sublingual tablet
Day 6: Methadone 1/2 Xmg per oral liquid; Buprenorphine 16mg daily sublingual tablet
Day 7: Methadone 1/4 Xmg per oral liquid; Buprenorphine 16-32mg daily sublingual tablet OR 16-32mg subcutaneous injection, at the discretion of the treating physician

From day 8, the intervention has ceased, and patients can be treated with buprenorphine at the discretion of the treating physician in line with current guidelines and recommendations.

Patients are to be reviewed each day prior to their morning dose. Supervised dosing will occur for all morning dosing. Unsupervised dosing will occur only the evening doses on days 1 and 2. These doses will be given to the patient on the morning of day 1 and 2 respectively.
Intervention code [1] 323068 0
Treatment: Drugs
Comparator / control treatment
Transfer of patients from methadone to buprenorphine using current standard of care as per NSW Health Guidelines (stop methadone, await withdrawal, commence buprenorphine). Patients will stop methadone, then wait to go into withdrawal. Patients will be commenced on buprenorphine 2mg when their clinical opioid withdrawal score is 13 or higher.
Control group
Active

Outcomes
Primary outcome [1] 330690 0
Success of transfer, defined as remaining on buprenorphine treatment 1 week post transfer. This will be assessed with a yes/no verbal question at a follow up appointment in person 1 week post day seven of the transfer
Timepoint [1] 330690 0
1 week post day 7 of the transfer
Secondary outcome [1] 407224 0
Continuation of buprenorphine at 1 month. This will be assessed with a yes/no verbal question at a follow up appointment in person 4 weeks post day seven of the transfer
Timepoint [1] 407224 0
4 weeks post day seven of the transfer
Secondary outcome [2] 407225 0
Rates of adverse events
- Precipitated withdrawal, defined as a rise in clinical opioid withdrawal score (COWS) of more than 6 within 6 hours of dose of buprenorphine. Assessed via clinical opioids withdrawal scale by a clinician from the study
- Adverse reaction to medication (buprenorphine). Assessed via patient self-report.
- Hospitalisation. Assessed via patient self-report
Timepoint [2] 407225 0
Daily review during transfer (days 1-7), then at 1 week follow up and 1 month follow up appointments
Secondary outcome [3] 407226 0
Length of hospital stay, collected at the final daily review for participants completing transfer in hospital. Assessed by review of medical record from clinician in the study
Timepoint [3] 407226 0
Duration of study
Secondary outcome [4] 407227 0
Rates of precipitated withdrawal – defined as rise in COWS by 6 within 6 hours from time of buprenorphine dose
Timepoint [4] 407227 0
Assessed daily for duration of study
Secondary outcome [5] 407228 0
Patient satisfaction with transfer and treatment outcome. Assessed by patient treatment satisfaction visual analogue scale at week four assessment
Timepoint [5] 407228 0
Week 4 assessment - 4 weeks post day seven of the transfer
Secondary outcome [6] 407229 0
Percentage of patients transitioned to depot buprenorphine, defined as patients on depot buprenorphine treatment at week 4 assessment. Assessed via yes/no question at week 4 assessment
Timepoint [6] 407229 0
Week 4 assessment - 4 weeks post day seven of the transfer

Eligibility
Key inclusion criteria
- Aged greater than or equal to 18 years
- Able to provide consent and comply with the study protocol
- Prescribed a stable dose of methadone for 5 days or more for opioid dependence
- Wanting to transfer to buprenorphine
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant
Unable to provide consent or comply with the study protocol
Contraindication to buprenorphine therapy
Allergy to buprenorphine therapy
Not currently prescribed methadone

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Nil
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Patient choice of treatment arm; allocated to arm with less participants if no preference
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Intention to recruit 120 patients across the study. Descriptive statistics to compare arms will involve objective measures of withdrawal and transfer (eg success yes/no), and subjective measures of patient satisfaction and withdrawal. Analysis to be completed in SPSS. We will aim to recruit 120 patients for our study. While there are case reports utilising this transfer method in the literature, the numbers are too few to know the expected outcomes in terms of success and adverse events. We feel this number will identify any safety problems we have with this regimen, and provide opportunity for titration of regimen accordingly.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
13/05/2021
Date of last participant enrolment
Anticipated
31/12/2022
Actual
14/02/2023
Date of last data collection
Anticipated
31/01/2023
Actual
13/03/2023
Sample size
Target
120
Accrual to date
Final
117
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21916 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 21917 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 21918 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 21919 0
John Hunter Hospital - New Lambton
Recruitment hospital [5] 21920 0
Drug and Alcohol Clinical Services, Hunter New England Local Health District - Newcastle
Recruitment hospital [6] 21921 0
NSLHD Drug and Alcohol Service - St Leonards
Recruitment hospital [7] 21922 0
Canterbury Hospital - Campsie
Recruitment hospital [8] 21923 0
Concord Repatriation Hospital - Concord
Recruitment hospital [9] 21924 0
The Langton Centre - Surry Hills
Recruitment hospital [10] 21925 0
Sydney Hospital and Sydney Eye Hospital - Sydney
Recruitment hospital [11] 21926 0
St George Hospital - Kogarah
Recruitment hospital [12] 21927 0
Brookvale Community Health Centre - Brookvale
Recruitment hospital [13] 21928 0
Tamworth Rural Referral Hospital - Tamworth
Recruitment hospital [14] 23185 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 37007 0
2000 - Sydney
Recruitment postcode(s) [2] 37000 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 37006 0
2010 - Surry Hills
Recruitment postcode(s) [4] 36999 0
2050 - Camperdown
Recruitment postcode(s) [5] 37001 0
2065 - St Leonards
Recruitment postcode(s) [6] 37009 0
2100 - Brookvale
Recruitment postcode(s) [7] 37005 0
2139 - Concord
Recruitment postcode(s) [8] 38551 0
2170 - Liverpool
Recruitment postcode(s) [9] 37004 0
2194 - Campsie
Recruitment postcode(s) [10] 37008 0
2217 - Kogarah
Recruitment postcode(s) [11] 37003 0
2300 - Newcastle
Recruitment postcode(s) [12] 37002 0
2305 - New Lambton
Recruitment postcode(s) [13] 37010 0
2340 - Tamworth

Funding & Sponsors
Funding source category [1] 310960 0
Other Collaborative groups
Name [1] 310960 0
Drug Health Services
Country [1] 310960 0
Australia
Primary sponsor type
Government body
Name
Drug Health Services, Royal Prince Alfred Hospital
Address
Drug Health Services
Royal Prince Alfred Hospital
Missenden Rd Camperdown
NSW 2050
Country
Australia
Secondary sponsor category [1] 312265 0
None
Name [1] 312265 0
Address [1] 312265 0
Country [1] 312265 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310519 0
SLHD Clinical Trials Sub-committee (RPAH Zone); SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 310519 0
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Ethics committee country [1] 310519 0
Australia
Date submitted for ethics approval [1] 310519 0
01/09/2020
Approval date [1] 310519 0
22/10/2020
Ethics approval number [1] 310519 0
Protocol no. X20-0369 & 2020/ETH02227

Summary
Brief summary
Buprenorphine and methadone are medications used in the treatment of opioid dependence. Buprenorphine is a partial opioid agonist, meaning it has a ceiling effect, and thus transferring from a full opioid agonist such as methadone can be challenging because of the risk of causing precipitated opioid withdrawal for the patient. Current standard practice is to reduce Methadone doses to lowest dose possible , wait until the patient is in moderate withdrawal, then commence buprenorphine. This can be a time-consuming process, often requiring hospital admission for a week, or even longer in some cases, putting additional strain on public health systems.

Micro-dosing is a novel approach to transitioning patients on full-agonist opioids (heroin, methadone, oxycodone, morphine) to buprenorphine using very small doses of buprenorphine concurrently with a full opioid agonist.

The aim of this prospective dual arm, clinical trial is to establish a safe micro-dosing regimen for completing transfers from methadone to buprenorphine, and compare outcomes in patients that undergo micro-dose transfers from methadone to buprenorphine to those completing a standard of care transfer.

Our hypothesis is that micro-dosing is a safe method for transitioning patients from methadone to buprenorphine in the community.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117934 0
Dr Chris Tremonti
Address 117934 0
C/O Royal Prince Alfred Hospital Drug Health Services
Level 6, King George V Memorial Building, Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Country 117934 0
Australia
Phone 117934 0
+61 413331136
Fax 117934 0
Email 117934 0
chris.tremonti@health.nsw.gov.au
Contact person for public queries
Name 117935 0
Dr Chris Tremonti
Address 117935 0
C/O Royal Prince Alfred Hospital Drug Health Services
Level 6, King George V Memorial Building, Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Country 117935 0
Australia
Phone 117935 0
+61 413331136
Fax 117935 0
Email 117935 0
chris.tremonti@health.nsw.gov.au
Contact person for scientific queries
Name 117936 0
Dr Chris Tremonti
Address 117936 0
C/O Royal Prince Alfred Hospital Drug Health Services
Level 6, King George V Memorial Building, Royal Prince Alfred Hospital
Missenden Rd
Camperdown 2050
Country 117936 0
Australia
Phone 117936 0
+61 413331136
Fax 117936 0
Email 117936 0
chris.tremonti@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not consented for by patients


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15346Study protocol    383719-(Uploaded-08-03-2022-17-12-32)-Study-related document.docx
15347Informed consent form    383719-(Uploaded-08-03-2022-17-13-13)-Study-related document.docx
15348Ethical approval    383719-(Uploaded-08-03-2022-17-13-52)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.