|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|The NEAT trial is for individuals with heroin addiction that have been diagnosed in the past year, but are not currently taking Heroin and want help to stay away from heroin.
|Psychiatry and Psychology [F] - Behaviours [F01]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|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 objectives of the trial
|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]);
injection health risk behaviours;
psychological health (depression and anxiety symptoms);
molecular (genetic) biomarkers of treatment response.
Plasma naltrexone and 6-β-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
|Trial contains a sub-study
|Principal 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.
|Principal 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:
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 compromise the participant’s ability to comply with the study protocol.
22. Current participation in any interventional trial, or completed participation in any interventional trial (which in the view of the chief investigator might interfere with the NEAT trial) within the last 3 months
|E.5 End points
|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 economic outcomes.
|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.
|Timepoint(s) of evaluation of this end point
|12 weeks from randomisation and at 16, 24 and 36 week follow-up.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|Expected clinical participation for each participant is from consent until the final follow-up at 36 weeks (38 weeks in total). The study will begin when the first participant gives consent and will end when the last participant has finished the follow up assessment at 36 weeks.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days