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Trial registered on ANZCTR


Registration number
ACTRN12621001729819
Ethics application status
Approved
Date submitted
20/08/2021
Date registered
17/12/2021
Date last updated
19/10/2023
Date data sharing statement initially provided
17/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility of Opioid Injectable Treatment
Scientific title
Implementation of time-limited parenteral hydromorphone in people with treatment-resistant injecting opioid use disorder: Feasibility, safety, and cost
Secondary ID [1] 304941 0
Nil Known
Universal Trial Number (UTN)
U1111-1268-4461
Trial acronym
FOpIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid Use Disorder 323092 0
Condition category
Condition code
Mental Health 320667 320667 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Supervised Injectable Opioid Treatment (SIOT) is an evidence-based treatment for dependent opioid injectors who have not responded to conventional, oral treatment. This project will implement SIOT as an adjunct to standard opioid agonist treatment (OAT) and explore whether benefits observed during injectable treatment are sustained after transfer to standard OAT. (Standard OAT is either methadone or buprenorphine). The 2-year, open-label non-controlled study will be located in an OAT clinic, where both methadone and buprenorphine are currently provided. We will recruit 20-30 long-term injectors of street opioid, prescribe a combination of parenteral hydromorphone and oral OAT, then around 18 months gradually transfer to standard OAT. Participants will self-administer (intravenous or intramuscular) twice-daily parenteral hydromorphone for 24-months under direct observation by nursing staff. Dosage range 50-400 mg/day (maximum 200 mg/dose). This will be followed by transition to oral agonist treatment (OAT) as per standard of care. The study period extends over 27 months (117 weeks).

The first phase of treatment is induction, the progressive increase in injected hydromorphone dosage, until the participant indicates they are comfortable on the dose, or until the maximum dose of 200mg bd is reached. The duration of this phase depends on the participants’ response but is anticipated to run for one week. During this phase the daily administered dose of OAT (methadone or buprenorphine) may also be adjusted to ensure there is no withdrawal experienced in the inter dosing interval. All dose changes are made with monitoring of clinical response using pulse oximetry, subjective and objective assessments. The induction schedule will be consistent with the Guidance for Injectable Opioid Agonist Treatment for Opioid Use (British Columbia Centre on Substance Misuse, undated). The specific dose for hydromorphone for each patient will be decided based on the patient’s rate of drug effect and assessment of patients pulse oximetry during a 15-minute post-injection observation. If after any dose during induction saturation falls to <90%, the next dose will be reduced by 25% and titration will continue. At any stage during induction, if participant reports being happy with the dose, no further increments will be implemented until participant requests a higher dose.

The second phase of treatment is stabilization (week 2 to week 4 following treatment initiation), with the dose administered twice a day that participant has indicated they were happy with in the first phase (maximum 200 mg/dose).

The third phase is maintenance (week 5 to week 78 following treatment initiation), typically with the same dose twice daily that the participant was stabilized on in phase 2 (maximum 200 mg/dose), allowing psychosocial issues to be addressed in regular clinical reviews (30 min review each fortnight administered by a Registered Nurse) until three months post last hydromorphone injection.

The fourth phase (weeks 79-104 following treatment initiation) is weaning of injections and progressive increase in oral OAT dose to ensure withdrawal symptoms are controlled. This weaning may last up to 6 months.

The final phase of treatment is a period of 3 months on oral OAT, to determine whether any gains made during injectable treatment are sustained once returned to conventional treatment.

Administration of oral methadone (or, if chosen by the participant, buprenorphine) is an integral part of this trial, since the long-term objective is to attract and hold in treatment people who have previously not responded to OAT; previous studies have demonstrated that the availability of injectable treatment is enough incentive to convert many “non-responders” to responders.
Intervention code [1] 321338 0
Treatment: Drugs
Comparator / control treatment
This is an uncontrolled feasibility study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329107 0
Feasibility as assessed by recruitment
Recruitment will be assessed based on the number of clients pre-screened, screened and enrolled to the study.
These data will be entered in the recruitment log under patient initials and date of birth. The recruitment log will document approaches, screening assessment, eligibility, participation, non-attendance during assessment and any reasons for non-participation after screening.
Timepoint [1] 329107 0
Six-months following study commencement
Primary outcome [2] 329109 0
Feasibility as assessed by retention on treatment. This outcome will be assessed by: a) # of days of injectable treatment; # days of oral medication only; # missed dosing days; and b). the # of clients successfully transferred to oral OAT as assessed at follow up interview.
Timepoint [2] 329109 0
27 months from treatment commencement
Primary outcome [3] 329110 0
Feasibility will be based on acceptability to patients undertaking SIOT. This outcome will be assessed in qualitative interviews contacted by researchers from University of New South Wales. The proposed interviews are semi-structured and seek to tap into expectations (positive and negative), accessibility and satisfaction with SIOT treatment, other positive and negative experiences of treatment, any negative effects (such as stigma), perceived mechanisms of change and treatment journey, practical issues associated with receiving treatment, and other themes as they arise in the interviews. All participants will be offered a qualitative interview.

Feasibility will be further assessed by qualitative interviews with 6-10 clinical staff working in Rankin Court during the study, 5-10 Rankin Court clients not involved in the study and 6-10 policy stakeholders.
Timepoint [3] 329110 0
For participants on SIOT qualitative interviews will be offered at baseline, 10-15 months and 3 months + 1 day after their last dose of hydromorphone.

Qualitative interviews with staff will occur between 12-18 months.

Qualitative interviews with other clients will occur between months 12 - 27.

Qualitative interviews with stakeholders will occur on completion of the clinical study between months 25 - 27
Secondary outcome [1] 399175 0
Safety (adverse events): This outcome will be assessed by descriptive statistics of adverse events elicited from participants at least fortnightly. Any spontaneously reported adverse events will be recorded after the subject signs the informed consent form.
Timepoint [1] 399175 0
Fortnightly throughout the treatment period.
Secondary outcome [2] 399595 0
Cost of time-limited injectable hydromorphone treatment.
A comprehensive cost assessment will be undertaken under the guidance of a health economist that will allow an accurate and detailed understanding of the costs associated with providing this new treatment. It will exclude trial-specific costs as these will not occur in other settings. The cost assessment will involve the collection of detailed data from a range of sources including health service utilisation interviews, electronic clinical records for prescribed medications and dose, actual patient/ clinician contact time, and diagnostic tests. The gathering of other information such as pharmacists’ time, dispensing activities, nurses monitoring of multiple clients at one time may require time/motion surveys. Where this is necessary, a stratified (by day of the week) random sample of days at the clinic will be utilised with detailed data collected by a research assistant on all relevant activities (then valued at the appropriate clinical staff rate). Given the importance of accuracy, we believe such an approach although more labour intensive, is required. Overheads costs will be established with the hospital finance team. The objective is to estimate both the unit cost of SIOT and minimum feasible number per site to inform scaling-up the treatment.
Timepoint [2] 399595 0
Month 3 post treatment commencement, onwards
Secondary outcome [3] 399597 0
Changes in opioid use (non-prescribed) in last 28 days.
# days heroin use; # days heroin injected; # of days non-prescribed/unsanctioned opioid use; # days injected non-prescribed/unsanctioned opioid use.
Self-report - Time Line Follow Back (TLFB)
Timepoint [3] 399597 0
Baseline, Month 12 (between 10-15 months after treatment commenced), Month 27 (between 1-3 months after treatment completed).
Secondary outcome [4] 399599 0
Changes in other drug use (non-prescribed) in last 28 days.
# of days used >4SD/day of alcohol;
# days used stimulants (amphetamine, cocaine, other stimulant) & # days injected stimulants;
benzodiazepines, # days used, # days injected
Self-report - TLFB
Timepoint [4] 399599 0
Baseline, Month 12 (between 10-15 months after treatment commenced), Month 27 (between 1-3 months after treatment completed).
Secondary outcome [5] 399600 0
Quality of life (changes).
This outcome will be assessed using the AQOL 8
Timepoint [5] 399600 0
Baseline, Month 12 (between 10-15 months after treatment commenced), Month 27 (between 1-3 months after treatment completed).
Secondary outcome [6] 399601 0
Mental health.
This outcome will be assessed using the K10 and SCL-90.
Timepoint [6] 399601 0
Baseline, Month 12 (between 10-15 months after treatment commenced), Month 27 (between 1-3 months after treatment completed).
Secondary outcome [7] 401502 0
Social connectedness and wellbeing (analysed as a composite outcome).
This outcome will be assessed using ATOP items 2a, 2b, 2c, 2d i.e. days of paid work, days in education, homeless or at risk of eviction in last four weeks.
Timepoint [7] 401502 0
Month 3 (after treatment commenced), Month 12 (between 10-15 months after treatment commenced), Month 27 (between 1-3 months after treatment completed).
Secondary outcome [8] 403174 0
Crime.
Assessed using a crime questionnaire
Timepoint [8] 403174 0
Baseline, Month 12 (between 10-15 months after treatment commenced), Month 27 (between 1-3 months after treatment completed).
Secondary outcome [9] 416699 0
Primary outcome: feasibility based on acceptability to staff (semi-structured interviews with around 8-10 clinical staff)
Timepoint [9] 416699 0
Interviews with staff conducted at month 12 (between Month 10 and Month 15) after first trial participants have been recruited.
Secondary outcome [10] 416700 0
Primary outcome: feasibility based on acceptability to other stakeholders (semi-structured interviews with 8-10 Rankin Court patients not enrolled in the trial (at Month 12 and Month 27); and with policy makers (n=6-10, at Month 27).
Timepoint [10] 416700 0
Interviews with other stakeholders conducted at Month 12 (between Month 10 and Month 15) after first trial participants have been recruited; and once first trial participants have completed treatment (Month 27). Interviews with policy makers conducted 27 months (between 1 and 3 months after treatment has ceased for first participants).
Secondary outcome [11] 416701 0
Physical health.
This outcome will be assessed by: ATOP Item J
Timepoint [11] 416701 0
Baseline, Month 12 (between 10-15 months after treatment commenced), Month 27 (between 1-3 months after treatment completed).

Eligibility
Key inclusion criteria
Participants should:
1. aged 21-60 years
2. have minimum 5 years opioid dependence, and current physical opioid dependence as assessed using ICD-10 criteria
3. had previous access to treatment
4. currently injecting opioids > 3 times weekly
5. have evidence of harm (self-reported crime, or comorbid health or mental health conditions, impaired social functioning)
6. have ability to provide written, informed consent to participate as assessed by trial medical staff
Minimum age
21 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. pregnant, breastfeeding, or planning to become pregnant (participants at risk of pregnancy should avoid pregnancy while receiving study treatment; participants who become pregnant will be transferred to oral Opioid Agonist Therapy [OAT])
2. advanced liver disease (Childs-Pugh B)
3. chronic airflow limitation or other respiratory compromise producing dyspnoea on mild exertion
4. other severe and active medical condition as assessed by study medical officer
5. requires prescribed medication which interacts with trial medication in ways which make treatment unsafe
6. severe psychiatric disorder at the time of assessment (e.g. acute psychosis, severe anxiety and/or mood disorder, intent to harm self or others assessed by study medical officer and/or psychiatrist).
7. severe cognitive impairment making it difficult for person to complete study requirements
8. previous adverse reaction to hydromorphone
9. concurrent monoamine oxidase inhibitors (MAOIs), or within 14 days of treatment with MAOIs
10. inability to provide informed consent, even with a registered medical interpreter

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be reported

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
20/04/2022
Actual
20/04/2022
Date of last participant enrolment
Anticipated
30/09/2022
Actual
4/10/2022
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
25
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20130 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 34851 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 309325 0
Hospital
Name [1] 309325 0
St Vincent's Hospital Sydney
Country [1] 309325 0
Australia
Funding source category [2] 309331 0
Government body
Name [2] 309331 0
National Health and Medical Research Council (NHMRC)
Country [2] 309331 0
Australia
Funding source category [3] 309332 0
Charities/Societies/Foundations
Name [3] 309332 0
Uniting
Country [3] 309332 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Sydney
Address
St Vincent's Hospital Sydney,
390 Victoria Street
Darlinghurst, NSW 2010
Country
Australia
Secondary sponsor category [1] 311282 0
None
Name [1] 311282 0
Address [1] 311282 0
Country [1] 311282 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309149 0
St Vincent's Hospital human Research Ethics Committee
Ethics committee address [1] 309149 0
Ethics committee country [1] 309149 0
Australia
Date submitted for ethics approval [1] 309149 0
12/03/2019
Approval date [1] 309149 0
24/05/2019
Ethics approval number [1] 309149 0
2019/ETH00418

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113154 0
Prof Nadine Ezard
Address 113154 0
Alcohol and Drug Service,
St Vincent's Hospital Sydney,
390 Victoria Street
Darlinghurst NSW 2010
Country 113154 0
Australia
Phone 113154 0
+61 02 8382 1012
Fax 113154 0
N/A
Email 113154 0
nadine.ezard@svha.org.au
Contact person for public queries
Name 113155 0
Nadine Ezard
Address 113155 0
Alcohol and Drug Service,
St Vincent's Hospital Sydney,
390 Victoria Street
Darlinghurst NSW 2010
Country 113155 0
Australia
Phone 113155 0
+61 457 474 854
Fax 113155 0
N/A
Email 113155 0
nadine.ezard@svha.org.au
Contact person for scientific queries
Name 113156 0
Nadine Ezard
Address 113156 0
Alcohol and Drug Service,
St Vincent's Hospital Sydney,
390 Victoria Street
Darlinghurst NSW 2010
Country 113156 0
Australia
Phone 113156 0
+61 02 8382 1012
Fax 113156 0
N/A
Email 113156 0
nadine.ezard@svha.org.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 Supporting Document Provided


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.