Condition category
Mental and Behavioural Disorders
Date applied
14/09/2007
Date assigned
27/09/2007
Last edited
26/09/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof John Strang

ORCID ID

Contact details

National Addiction Centre
Addiction Sciences Building
4 Windsor Walk
Denmark Hill
London
SE5 8AF
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

KCL/SLaM-CT2004-3

Study information

Scientific title

Acronym

RIOTT (Randomised Injectable Opioid Treatment Trial)

Study hypothesis

The research objective of the trial is to examine the safety, efficacy and cost effectiveness of treatment with injectable methadone or injectable heroin compared to optimised oral methadone treatment, for patients not responding to their current oral maintenance treatment episode.

Hypotheses:
1. A selected group of patients (not responding to usual oral methadone treatment) receiving injectable heroin treatment or injectable methadone treatment, will make greater reductions in their illicit heroin use, other drug use and criminal activity and greater improvements in their health and social functioning, than if provided with optimised oral methadone treatment
2. Providing injectable heroin or injectable methadone to a selected group of patients (not responding to usual oral methadone treatment) results in a greater economic benefit per extra unit of resource invested in the treatment, than only offering optimised oral methadone

Ethics approval

1. Institute of Psychiatry Ethics Committee for single-site study, 26/02/2004, ref: 291/03
2. London MREC for multi-site study, 03/06/2006, ref: 06/MREC02/22

Study design

Multi-site open-label randomised controlled trial to compare the safety, efficacy and cost-effectiveness of prescribing injectable opiates versus optimised oral methadone

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Opiate dependence/addiction

Intervention

Patients randomised to receive optimised oral methadone treatment will receive methadone treatment under enhanced conditions. The intervention will include high methadone doses (at least 80 mg), supervised dispensing of medications contingent upon levels of unsanctioned drug use (daily supervised dosing initially), and patients will be expected to attend for regular key worker and medical appointments. Methadone is a semi-synthetic opioid used in the treatment of opioid drug dependence to prevent opioid withdrawal syndrome by substituting for heroin.

The injectable methadone group will receive treatment with once-daily injectable (intraveous [IV]/intramuscular [IM]) methadone ampoules. There will be full supervision of all injected doses. Patients will be expected to attend for regular key worker and medical appointments. Patients will be able to supplement their injectable methadone dose with prescribed oral methadone doses. Methadone Hydrochloride B.P. for injection is a colourless, preservative and oxidant free solution in clear glass ampoules.

Those receiving injectable heroin will receive treatment with injectable (IV/IM) heroin ampoules, administered under supervision up to twice a day. Patients will be expected to attend for regular key worker and medical appointments. Patients will be able to supplement their injectable heroin dose with prescribed oral methadone doses. Diacetylmorphine hydrochloride (Diamorphine hydrochloride, heroin hydrochloride, heroin) is a opioid used in the treatment of opioid drug dependence. All injections are supervised in the clinic.

All those receiving injectable treatment or optimised oral methadone treatment will receive named keyworker and frequent reviews and ancillary services. The total duration of treatment and follow-up is 6 months.

Intervention type

Drug

Phase

Not Specified

Drug names

Heroin, methadone

Primary outcome measures

Reduction in illicit heroin, measured by urine drug screens taken on a weekly basis over 6 months.

Secondary outcome measures

Self-reported to researcher at baseline, 3 months and 6 months (in or out of treatment):
1. Changes in illicit heroin use:
1.1. Number of days used illicit heroin in past 30 days
1.2. No days injected/smoked/snorted illicit heroin in past 30 days
1.3. Average cost of illicit heroin on days used
1.4. Frequency of use in past month, as measured by the Drug Use Section of Opiate Treatment Index (OTI Q score)
2. Changes in other illicit opiate drug use (non-prescribed):
2.1. Injectable opioid pharmaceuticals (methadone, heroin)
2.1.1. Days used in past 30 days
2.1.2. Average cost
2.1.3. Estimate quantity on average day of use
2.2. Oral methadone/morphine:
2.2.1. Days used in past 30 days
2.2.2. Average cost
2.2.3. Estimate quantity on average day of use
2.3. Codeine/codeine like preparations:
2.3.1. Days used in past 30 days
2.3.2. Average cost
2.3.3. Estimate quantity on average day of use
3. Changes in illicit cocaine use:
3.1. Number of days used crack/cocaine in past 30 days
3.2. No days injected/smoked/snorted in past 30 days
3.3. Average cost of cocaine on days used
4. Other illicit drug use and alcohol - benzodiazepines, alcohol, cannabis:
4.1. No days used past 30 days
4.2. Average quantities consumed (estimated as diazepam mg equivalents; units alcohol; grams cannabis)
4.3. Average cost of each drug used on average day
5. Changes in high-risk injecting practices:
5.1. Participation in risk practices for blood borne virus transmission in preceding month using the Injecting Risk Questionnaire, with responses pegged according to number of times occurred in the past month
5.2. Assessment of injecting practices using self-report scale developed for the trial
6. Changes in general health status:
6.1. 36-item Short Form health survey (SF-36)
6.2. Euro-QoL instrument (EQ-5D)
7. Changes in psychosocial functioning:
7.1. 36-item Short Form health survey (SF-36)
7.2. Euro-QoL instrument (EQ-5D)
7.3. Psychosocial Adjustment Section of the OTI
8. Changes in criminality: self-report using adapted OTI Crime Section of MAP
9. Use of other health and social services: health, social and voluntary sector services used, days off work due to illness, criminal justice sector contacts - adapted REDUCE questionnaire for cost effectiveness analysis
10. Measures of patient expectation of and satisfaction with treatment
10.1. Treatment Perceptions Questionnaire
10.2. Drug Use, Expectations and Satisfaction Questionnaire to measure benefits and problems with using street heroin (developed for the trial) and expectations and satisfaction of treatment received whilst on trial (developed for trial)

In addition, we are monitoring injecting practices and complications, any post dosing side effects and serious and non-serious adverse event data and collecting data on retention.

Overall trial start date

01/07/2004

Overall trial end date

30/06/2008

Reason abandoned

Eligibility

Participant inclusion criteria

The selection criteria targets heroin users with a long-standing history of injecting heroin use who continue to inject heroin frequently whilst in their current episode of methadone treatment. Selection criteria include:
1. History of injecting heroin use sufficient to meet Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria
2. Aged between 18 and 65 years at recruitment to study
3. In continuous methadone treatment for at least 6 months this episode
4. Regular injecting heroin use

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

150

Participant exclusion criteria

1. No active significant medical (e.g., hepatic failure) or psychiatric condition (active psychosis, severe affective state) as determined by study medical officer
2. Not alcohol dependent or abusing benzodiazepines according to DSM-IV revised criteria
3. Not pregnant, breast feeding, or planning to become pregnant during the study period
4. Able and willing to participate in the study procedures (e.g., no impending prison sentence) and provide informed consent

Recruitment start date

01/07/2004

Recruitment end date

30/06/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

National Addiction Centre
London
SE5 8AF
United Kingdom

Sponsor information

Organisation

South London and Maudsley NHS Foundation Trust and Kings College London (UK)

Sponsor details

c/o Dr Gill Dale
Director of Research Quality
Joint R&D Office of South London and Maudsley NHS Foundation Trust and Institute of Psychiatry
P005 Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom

Sponsor type

Government

Website

http://www.kcl.ac.uk/

Funders

Funder type

Charity

Funder name

Action on Addiction (UK) - Big Lottery Fund (research part of trial) (ref: PR/1/010256258)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Treatment Agency (UK) - clinical part of trial (ref: 2007/08)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20511018
2014 secondary outcome results in: http://www.ncbi.nlm.nih.gov/pubmed/25251885

Publication citations

  1. Results

    Strang J, Metrebian N, Lintzeris N, Potts L, Carnwath T, Mayet S, Williams H, Zador D, Evers R, Groshkova T, Charles V, Martin A, Forzisi L, Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial., Lancet, 2010, 375, 9729, 1885-1895, doi: 10.1016/S0140-6736(10)60349-2.

  2. Secondary outcome results

    Metrebian N, Groshkova T, Hellier J, Charles V, Lintzeris N, Zador D, Williams H, Carnwath T, Mayet S, Strang J, Drug use, health and social outcomes of hard-to-treat heroin addicts receiving supervised injectable opiate treatment: secondary outcomes from the Randomized Injectable Opioid Treatment Trial (RIOTT)., Addiction, 2014, doi: 10.1111/add.12748.

Additional files

Editorial Notes