Opiate addiction MedDRA version: 18.1 Level: LLT Classification code 10019935 Term: Heroin addiction System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Naltrexone Hydrochloride 50 mg film-coated tablets
Product Name: Naltrexone Hydrochloride 50mg film-coated Tablets
Pharmaceutical Form: Film-coated tablet
Sponsors
King's College London
South London and Maudsley NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for the study are intended to be as close to clinical practice as possible. Each participant in the trial must meet all of the following criteria: 1. Is 18 years of age or older. 2. Can demonstrate a verbal understanding of the study patient information material, is able to provide written consent, and can understand and confirm willingness to comply with the protocol. 3. Has a diagnosis of opioid use disorder based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5: past 12 months),) conducted at baseline. 4. Is completing or has recently completed an inpatient or outpatient treatment for opioid detoxification, or has been completely and continuously abstinent from all opioids for at least seven days. 5. Has no tolerance to opioids, as verified by a negative urine toxicology screening test prior to randomisation (using an instant result immunoassay device). 6. Passes a naloxone challenge test (to confirm zero opioid tolerance by demonstrating no clinical sign or subjective report of opioid withdrawal before randomisation and prior to implant procedure) NB: Individuals failing screening will be allowed to enter screening as clinically indicated. 7. Is voluntarily seeking opioid antagonist treatment for opioid use disorder. 8. Lives in stable/secure accommodation in the community. 9. Has a personal (mobile/cellular) phone, and is able to nominate at least one locator individual (e.g. a family member, friend or recovery mentor) with a verifiable address and a telephone number to assist with the arrangement of follow-up appointments as required. 10. If female, is not pregnant or breast feeding and agrees to use a birth control method (either oral hormonal contraceptives, barrier [condom or diaphragm], or Nexplanon implant) for the duration of the study. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: Otherwise eligible individuals who meet any of the following criteria will be excluded from the study: 1. Clinically significant medical condition or observed abnormalities on physical examination or laboratory investigation, including but not limited to: ? Uncontrolled hypertension; ? Significant heart disease (including angina and myocardial infarction in past 12 months); ? Any ECG/cardiovascular abnormality which, in the investigator’s judgment, is clinically significant. 2. Severe alcohol dependence and/or alcohol withdrawal (by clinical assessment). 3. Opioid withdrawal syndrome, current. 4. Positive test for presence of opioids in urine (i.e. indicating current opioid use) prior to randomisation (using an instant result immunoassay device). 5. Clinical diagnosis of opioid dependence syndrome (F11.2) with current physical dependence such that an antagonist medication (e.g. naloxone, naltrexone) could precipitate a withdrawal syndrome 6. Positive naloxone challenge test at randomization (confirming opioid use) or absence of a recorded result from a naloxone provocation test. 7. Acute hepatitis taken as clinical jaundice on examination and/or blood bilirubin level >normal range for local reference criteria or aspartate aminotransferase or alanine aminotransferase (>3x the upper limit of the normal range). 8. Hepatic insufficiency (taken as >3 times the upper limit of the normal range of aspartate aminotransferase or alanine aminotransferase) 9. Severe renal impairment evaluated by clinical decision 10. Known Icenko-Cushing syndrome or to require investigation if suspected Cushingoid features/symptoms 11. Systemic mycoses 12. Clinical history of glaucoma 13. Clinical history of osteoporosis 14. pregnancy, or positive or unclear test result from pregnancy test, or intention to try to become pregnant during the study period, or is sexually active without using a birth control method (either oral hormonal contraceptives, barrier [condom or diaphragm], or Nexplanon implant) for the duration of the trial. 15. Currently breast-feeding 16. History of hypersensitivity to opioid receptor blockers (naloxone and naltrexone formulations) and other components of the formulation. 17. History of hypersensitivity to triamcinolone or related compounds 18. Currently taking oral or depot naltrexone therapy or enrolment in any form of naltrexone therapy within 90 days prior to study screening, apart from treatment given by trial team between screening and randomisation. 19. Current criminal justice involvement with legal proceedings (not including current probation supervision) and, in the opinion of the clinical worker, is expected to fail to complete the study protocol due to re-incarceration or relocation from the centre’s catchment area. 20. Current (past 30 day) suicidal planning, or recent (past six months) suicide attempt. 21. Active, uncontrolled severe mental illness (e.g. psychosis, bipolar I disorder, schizoaffective disorder) and/or a history or evidence of organic brain disease or dementia that would comprom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: A. Is XR-NTX treatment more effective than placebo at reducing heroin use? B. Is XR-NTX more effective than O-NTX at reducing heroin use? C. Is XR-NTX more cost- effective than placebo in terms of quality-adjusted life years? D. Is XR-NTX more cost-effective than O-NTX in terms of quality-adjusted life year? ; Secondary Objective: A. To compare treatment retention and medication and psychological intervention adherence rates among the XR-NTX, O-NTX and placebo conditions. B. To contrast the XR-NTX, O-NTX and placebo conditions on quality of life indices. C. To contrast XR-NTX, O-NTX and placebo conditions on: ? heroin and cocaine craving; ? self-reported opioid, cocaine, amphetamine and benzodiazepine use (with past 48 hour abstinence verified via urine drug screening [UDS]); ? alcohol use; ? injection health risk behaviours; ? psychological health (depression and anxiety symptoms); ? molecular (genetic) biomarkers of treatment response. ? Plasma naltrexone and 6-ß-naltrexol (the primary metabolite of NTX); D. To document the safety of XR-NTX and O-NTX. E. To compare patterns of heroin relapse among the XR-NTX, O-NTX and placebo conditions ; Primary end point(s): Clinical: the proportion of heroin negative UDS results at the end of the 12 week post-randomisation period (denominator 36), with contrasts for: (i)XR-NTX vs. placebo, and (ii) XR-NTX vs. O-NTX. Economic: health related quality of life and cost-effectiveness at 36 weeks with comparisons for (i) XR-NTX vs. placebo, and (ii) XR-NTX vs, O-NTX. ;Timepoint(s) of evaluation of this end point: 12 weeks post-randomisation for clinical outcome and 12 weeks and 36 weeks follow up for the health ec | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 12 weeks from randomisation and at 16, 24 and 36 week follow-up.;Secondary end point(s): Treatment retention, adherence, heroin and cocaine craving scores, self-reported opioid, cocaine, benzodiazepine (and their active class metabolites via urine drug screening), and alcohol use, injection health risk behaviours, psychological health (depression and anxiety symptoms), and health-related quality of life results over the 12 weeks from randomisation and at 16, 24 and 36 week follow-up. | — |
Countries
United Kingdom
Contacts
Public ContactBlair McLennan, NEAT Trial Manager
Institute of Psychiatry, Psychology & Neuroscience (IoPPN)
Outcome results
None listed