Intensive care patients requiring sedation in order to facilitate mechanical ventilation Other
Conditions
Interventions
Single arm, non-randomised, open-label study of continuous intravenous ketamine infusions.
The use of continuous ketamine infusions will follow the regimens used in recent trials and will be calculate
Sponsors
Leeds Teaching Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Requiring mechanical ventilation on ICU 2. Aged 18 years or older 3. Within 48hrs of starting mechanical ventilation 4. Requiring sedation 5. Expected to require more than 48hrs of mechanical ventilation 6. Expected to require a further 24hrs of mechanical ventilation at time of eligibility
Exclusion criteria
Exclusion criteria: 1. Acute brain injury (hypoxic, traumatic, ischaemic, haemorrhagic) at time of screening 2. Acute central nervous system infection (including meningitis and encephalitis) at time of screening 3. Acute liver failure (Hyper-acute, acute, or sub-acute liver failure as defined by O’Grady et al33*) at time of screening 4. Acute liver injury (ALT >400iu/L ± INR>1.5 in absence of other causes)** at time of screening 5. Acute myocardial infarction or known severe coronary or myocardial disease at time of screening 6. Allergy to ketamine or any of its formulation excipients, or allergy to alfentanil 7. Continuous neuromuscular paralysis at time of screening 8. Decision to provide only palliative or end-of-life care by clinical team at time of screening 9. Drug induced / malignant hyperpyrexia at time of screening 10. Enrolled in another CTIMP or any ICU study at time of screening 11. Home ventilation (including overnight non-invasive ventilation / CPAP) 12. Liver transplant recipient at any point in participant’s medical history 13. Long-term medical condition resulting in the participant lacking capacity prior to current illness, and who is not expected to ever regain capacity to provide consent to participate after cessation of sedation 14. Neuromuscular junction disorder as admitting or contributing diagnosis (e.g. Guillain-Barre, myasthenia gravis etc.) at time of screening 15. Patient not expected to survive >24 hours at time of screening 16. Patient known to be taking / prescribed ergometrine or memantine (severe interaction with IMP) 17. Post cardiac arrest where there is clinical concern of acute hypoxic brain injury at time of screening 18. Pregnancy***, up to 6 weeks post-partum (following delivery), suspected eclampsia / pre-eclampsia, or breast feeding / expressing milk 19. Previously enrolled into SHOCK-ICU 20. Psychosis or any mental health illness requiring treatment at time of screening 21. Raised intra-ocular pressure (suspected, confirmed, or history of****) 22. Severe hypertension (systolic blood pressure >180mmHg) at time of screening 23. Tachyarrhythmia (ventricular and supraventricular) at time of screening excluding atrial fibrillation with rapid ventricular response or sinus tachycardia in the context of a precipitating cause e.g. sepsis 24. Transferred from another ICU in which MV occurred for >6 hours 25. Prisoner or detained in police custody prior to admission * O’Grady jaundice to encephalopathy time intervals: Hyper-acute = <7 days, acute = 8-28 days, sub-acute = 5-12 weeks.33 **These tests should be performed and recorded in the medical notes as part of the standard of care for ICU patients. Any potential participants in this category without liver function tests from the previous 7 days at the time of eligibility screening will be excluded from participation. *** Any woman of childbearing potential (as defined by Clinical Trials Facilitation and Coordination Group34 i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation includes hysterectomy, bilateral salpingectomy and bilateral oophorectomy) lacking capacity with a possibility of being pregnant should have a pregnancy test performed and recorded in the medical notes as part of the standard of care for ICU patients. Any potential participants in this category without a valid negative pregnancy test at the time of eligibility screening will be excluded from participation. **** It is not a requ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Study process measurements: 1.Recruitment and refusal rates (Frequencies and percentages) - Continuously during study period and at the end of the study period 2.Withdrawal and follow-up rates (Frequencies and percentages) - Continuously during study period and at the end of the study period 3.Withdrawal and refusal reasons (Frequencies and percentages) - Continuously during study period and at the end of the study period Ability to collect data measurements: 4.Standard of care data completeness for proposed clinical efficacy markers (Frequencies and percentages) - At the end of the study period 5.Ability to collect PROMs at ICU discharge and 90-day follow-up (Frequencies and percentages) - At the end of the study period 6.Ability to collect health economic data during study period (Frequencies and percentages) - At the end of the study period Staff feedback measurements: 7.Feedback on ability to provide intervention and care for study participants (Anonymous categorical data via Google forms) - At the end of the study period Reliability measurements: 8.Correct / accurate recording and formatting of representative sample of CRFs (Frequencies and percentages) - At the end of the study period 9.Completeness of representative sample of CRFs (Frequencies and percentages) - At the end of the study period Level of safety and adverse event measurements: 10.Incidence of AEs /SAEs, ARs, SUSARs (Numerical and categorical data) - Continuously from enrolment until ICU discharge Exploratory assessment of clinical efficacy measurements: 11.Ability to collect proposed clinical efficacy measurements (Frequencies and percentages) - At the end of the study period 12.Ability to collect exploratory outcome measurements (Frequencies and percentages) - At the end of the study period | — |
Secondary
| Measure | Time frame |
|---|---|
| There are no secondary outcome measures | — |
Countries
England, United Kingdom
Contacts
Public ContactNicholas;Nicholas Richards;Richards
;
Outcome results
None listed