Critical illness Other
Conditions
Interventions
This is a platform trial with multiple arms running within the protocol appendices called Trait Specific Protocols (TSPs). Each TSP recruits different sub set of TRAITS participants and randomises to
Sponsors
Accord (United Kingdom)
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: Platform inclusion 1. Aged =18 years 2. Provision of consent (including deferred consent in accordance with Section 5.2) 3. Receiving organ support in a critical care setting 4. Organ dysfunction of at least one organ (SOFA Score>=2) 5. In clinical team’s opinion is likely to require organ support* for =24 h post randomisation 6. Resident in Scotland (required for ongoing data linkage) *Organ support is defined as treatments provided in the critical care units to support one or more of the organ systems, as per the critical care minimum dataset (please see link: https://www.datadictionary.nhs.uk/attributes/organ_system_supported.html). Respiratory support refers to provision of invasive or non-invasive mechanical ventilation, including high-flow nasal cannula with a flow rate =30 L per minute and fractional inspired oxygen concentration =30%). Cardiovascular support refers to infusion of vasopressor or inotropes. Renal support refers to provision of renal replacement therapy. Appendix 1: LYMP-RESP TSP inclusion 1. Provision of consent 2. Respiratory dysfunction is defined as PaO2/FiO2 ratio =12 x 10(9)/L. The CRP levels and neutrophil count measurements from blood samples done as part of routine clinical care, around the time of trait eligibility assessment (+/- 36 h window) could be used. The time window of +/- 36 h reflects the current routine clinical care.
Exclusion criteria
Exclusion criteria: Platform exclusion 1. In the Investigator’s opinion, the participant is unwilling or unable to comply with the trial intervention and/or procedures 2. Patients was admitted to ICU more than 48 h ago 3. Primary neurological ICU diagnosis 4. Neuromuscular disease and long-term home ventilation 5. Organ transplantation within 90 days 6. Patient not expected to survive 24 hours by the clinician responsible for clinical care 7. Decision to provide only palliative or end-of-life care 8. Prisoners 9. Previous randomisation on the TRAITS trial 10. Individuals with permanent incapacity 11. Known or suspected pregnancy [Note: pregnancy test result is not required for women of childbearing potential (WOCBP) when assessing platform eligibility] 12. Breast feeding Appendix 1: LYMP-RESP TSP exclusion Generic 1. Known hypersensitivity to study products or any of its excipients (excipients listed in section 6.1 of the representative SmPC) 2. More than 48 h has elapsed since ICU admission. 3. Patient is known to be pregnant. (A pregnancy test in females with childbearing potential (aged 15-55 years) will be performed prior to enrolment and patients who are pregnant will be excluded. 4. Breastfeeding Intervention-specific exclusion criteria - Budesonide 5. Patient is already receiving, or a clinical decision has been made to commence inhaled or intravenous corticosteroids Intervention-specific exclusion criteria – Baricitinib 6. Patients with active TB 7. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product. Diagnosis of sepsis is not a contraindication, given that COVID-19 patients will meet the sepsis case definition. 8. Have received any live vaccine within 4 weeks before screening 9. Alanine aminotransferase (ALT) or an aspartate aminotransferase (AST) > 5 times the upper limit of the normal range 10. Estimated glomerular filtration rate (eGFR) of less than 30 mL/min per 1.73 m², immediate need for hemodialysis or hemofiltration; 11. In the opinion of the investigator, unlikely to survive for at least 48 h after screening. 12. Have neutropenia (absolute neutrophil count <1x10(9) cells/L) 13. Have severe lymphopenia (absolute lymphocyte count <0.20x10(9) cells/L) Appendix 2: ENDO-SHOCK TSP exclusion Generic 1. Known hypersensitivity to imatinib or any of its excipients (excipients are listed in section 6.1 of the representative Summary Product of Characteristics (SmPC), 2. More than 48 h has elapsed since ICU admission. 3. Patient is known to be pregnant. (A pregnancy test in females with childbearing potential (aged 15-55 years) will be performed prior to enrolment and patients who are pregnant will be excluded. 4. Breastfeeding Intervention-specific exclusion criteria – Imatinib 5. Patient is already receiving, or a clinical decision has been made to commence imatinib or another tyrosine kinase inhibitor targeting the same pathway as imatinib (i.e. dasatinib, nilotinib, ponatinib) 6. Patient was receiving imatinib or another tyrosine kinase inhibitor targeting the same pathway as imatinib (i.e dasatinib, nilotinib, ponatinib) prior to this hospital admission 7. The treating clinician believes that participation in the domain would not be in the best interests of the patient 8. Severe liver disease or alanine aminotransferase (ALT) or an aspartate aminotransferase (AST) that is more than fi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. For the overall trial (i.e., referred to as stage-2 evaluation of interventions within each trait), the primary endpoint is number of Organ Support Free Days (OSFD) during the first 21 days from randomisation. This will apply to all treatable traits. Where the participant dies within the first 21 days, the OSFD primary endpoint will be assigned a value of minus 1. 2. For the intermediate adaptive analyses (i.e., stage-1 evaluations of interventions within each treatable trait), the intermediate endpoint will be specific for each treatable trait, and therefore highlighted in trait specific protocols. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are those included in the core-outcome set for mechanical ventilation measured using patient records, including: 1. Mortality at different time-points 2. Organ support free days in ICU 3. Days alive outside the hospital (hospital-free days) at 180 days of randomisation This will apply to all treatable traits. Additional secondary outcomes may be included in trait-specific protocols. | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactFiona Wee
Outcome results
None listed