TRAITS Programme: Precision medicine trials for adults treated in critical care units
- Conditions
- Critical illnessNot Applicable
- Registration Number
- ISRCTN82395639
- Lead Sponsor
- niversity of Edinburgh
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 2000
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 <40 KPa whilst receiving respiratory support with either non-invasive ventilation (including high flow nasal cannula) or invasive mechanical ventilation for 6 hours or longer. Arterial blood gas samples taken within 3 hours of trait eligibility assessment can be used to determine the PaO2/FiO2 criteria.
3. Lymphopenia defined as lymphocyte count <1.2 x 10(9)/L. The lymphocyte count measurements from blood samples done as part of routine clinical care, +/- 36 h of critical care admission could be used. The time window of +/- 36 h reflects the current routine clinical ordering of full blood counts.
Appendix 2: ENDO-SHOCK TSP inclusion
1. Provision of consent
2. Presence of shock: defined as hypotension requiring vasopressor therapy to maintain mean blood pressure 65 mm Hg or greater (equates to cardiovascular SOFA score of 2 or more) and having a blood lactate level greater than 2 mmol/L after adequate initial fluid resuscitation. The term adequate is a clinical judgement. The term initial fluid resuscitation refers to the first set of fluid administration in patients presenting with shock, and acknowledges the fact that resuscitation is an ongoing process. The lactate measurement done as part of routine clinical care using either arterial or venous blood gas, around the time of resuscitation could be used.
3. Evidence of inflammation: defined as C-reactive protein (CRP) 50 mg/L or more OR neutrophil count >=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.
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,
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 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.<br> 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.<br>
- Secondary Outcome Measures
Name Time Method <br> Secondary endpoints are those included in the core-outcome set for mechanical ventilation measured using patient records, including:<br> 1. Mortality at different time-points<br> 2. Organ support free days in ICU<br> 3. Days alive outside the hospital (hospital-free days) at 180 days of randomisation<br> This will apply to all treatable traits.<br><br> Additional secondary outcomes may be included in trait-specific protocols.<br>