Opioid Overdose MedDRA version: 21.1 Level: PT Classification code 10033295 Term: Overdose System Organ Class: 10022117 - Injury, poisoning and procedural complications MedDRA version: 20.0 Level: LLT Classification code 10033299 Term: Overdose effect System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Product Name: Diamorphine Hydrochloride BP
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Diamorphine hydrochloride
CAS Num
Sponsors
South London and Maudsley NHS Foundation Trust
King's College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diamorphine-injecting subjects who have been in treatment for a minimum of one month; 2. Male or female; 3. = 18 years; 4. Capable of providing voluntary written informed consent; 5. A non custodial stable residence and telephone number; 6. Venous access has to be suitable for intravenous drug administration and cannula insertion NB: only intravenous injecting users will be included in this study, however, for trial purposes, intramuscular administration of the IMP will be used if peripheral venous access is not appropriate on the study days; 7. Oxygen saturation reading of =92%; 8. Forced expiratory volume in 1 second ratio, predicted % (FEV1%) of >50% (spirometry); 9. Absence of acute respiratory illness for 6 weeks prior to screening or any study day. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1. Dependent use of cocaine or amphetamines requiring specific treatment. This will be assessed at Pre-Study Screen. 2. Active significant medical condition (e.g. hepatic failure or severe hepatic disease) as determined by clinical assessment, medical history and as advised by their treating clinician. This will be assessed by the clinical investigator at Pre-Study Screen, for example: i. Severe hepatic insufficiency (liver function tests conducted within the last 6 months prior to screening): Patients with clinical features of hepatic failure (e.g. encephalopathy, ascites, jaundice, prolonged bleeding, hypoalbuminaemia and secondary oedema – consistent with Child-Pugh Classification B or C). Patients with liver disease (e.g. HCV, HBV infection) without features of hepatic failure are potentially eligible. ii. Severe respiratory insufficiency or the inability to reliably perform physiological tests of respiratory function (spirometry). iii. Pre-existing renal or cardiac issues that the study physician or treating clinician considers inappropriate for the purposes of this trial. 3. In cases where subjects are able to perform spirometry, a FEV1% of =50% as confirmed by spirometry at Pre-Study Screen. 4. Oxygen saturation reading of <92% as confirmed by finger pulse oximetry at Pre-Study Screen. 5. Acute illnesses that make participation inappropriate, as assessed by the study physician. Presence of acute respiratory illness within 6 weeks prior to screening or any of the study sessions. This will be assessed during screening and on each study day. If acute illness is present, subject will be asked to return 6 weeks post-acute illness. Acute diarrhoeal conditions caused by antibiotic-induced pseudomembranous colitis or by poisoning will be assessed by the study physician. Assessment at Pre-Study Screen and on each Study Visit. 6. Subjects suffering from acute alcoholism or delirium tremens. This will be assessed at Pre-Study Screen. 7. Subjects who have suffered from head injury or have been with diagnosed phaeochromocytoma. These will be assessed at Pre-Study Screen. 8. Risk of paralytic ileus or biliary colic assessed by the study physician. This will be assessed at Pre-Study Screen. 9. A benzodiazepine prescription that is above the standard therapeutic dose range (e.g. if oral Diazepam above 30mg/daily; BNF, 2016). This will be examined by medical notes at the Pre-Study Screen. A drug test on each Study Visit will be performed to assess whether there is any presence of benzodiazepines that the participant is not prescribed. Concomitant medication check will also be conducted at Pre-Study Screen. 10. Subjects prescribed other contraindicated drugs: monoamine oxidase inhibitors (or within 2 weeks of their discontinuation), 4-quinolone antibacterials, phenothiazines, tricyclic antidepressants, anxiolytics (see above), hypnotics, cisapride, domperidone and metoclopramide, cimetidine and selegiline. This will be assessed at Pre-Study Screen. 11. Alcohol and other drug use on the specific study days. A drug screen (Angelscope) and breathalyser (BACtrack, Xtend®) will be used to confirm additional drug/alcohol use on the study days. A positive drug screen (excluding prescribed drugs) and an excessive blood alcohol content
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate respiratory depression and hypoxaemic response to intravenous (IV) or intramuscular (IM) higher-than-regular doses of heroin as a marker for overdose; Secondary Objective: To investigate effect of variations in heroin dose on subjective drug effect and whether these are correlated to physiological changes To investigate the unique arms movements of injecting (IV) heroin using wearable devices (motion signature) To monitor variation in breathing patterns (rhythm) using wearable devices (Apple watch or similar) ; Primary end point(s): Primary endpoints will be to assess: • Blood oxygen saturation (SpO2), • End-tidal carbon dioxide (ETCO2), • Transcutaneous carbon dioxide (TcCO2), and • Intercostal parasternal electromyography to measure neural respiratory drive ;Timepoint(s) of evaluation of this end point: All endpoints will be obtained by measurements taken during the study visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be to assess: • Pupil size • Subjective drug effects (using visual analogue scale) • Staff rating of drug effects (using visual analogue scale) • Arm movement using the three-axis gyroscope, accelerometer, and magnetometer embedded in the wrist watch (Apple Watch or similar) • Respiratory pattern (rhythm) using the microphone embedded in the wrist watch (Apple Watch or similar) ;Timepoint(s) of evaluation of this end point: All endpoints will be obtained by measurements taken during the study visits. | — |
Countries
United Kingdom
Contacts
Public ContactProfessor John Strang
South London and Maudsley NHS Foundation Trust
Outcome results
None listed