Septic shock Infections and Infestations Infection/ Other infectious diseases, Inflammatory and Immune System/ Certain disorders involving the immune mechanism
Conditions
Interventions
Current interventions as of 28/02/2019:
Participants are randomised to receive standard treatment with the addition of a beta blocker infusion (landiolol) or standard treatment alone.
For those in t
Sponsors
University Hospitals Birmingham NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 14/08/2020: 1. Aged 18 years or above 2. Being treated on an ICU 3. Septic shock according to internationally accepted definitions* 4. Heart rate =95 bpm ( at the time of randomisation) 5. Receiving vasopressor support to maintain a target blood pressure for =24 hours 6. Are being treated with noradrenaline at a rate = 0.1 mcg/kg/min *Sepsis -3 definitions: 1. Confirmed or suspected infection requiring antibiotic therapy 2. New organ dysfunction, as evidenced by an increase in SOFA score =2 3. A blood lactate >2 mmol/l at any point during shock resuscitation 4. Vasopressor therapy to maintain mean arterial pressure (MAP) =65 mmHg In particular the presence of a blood lactate > 2 mmol/l is only necessary for the diagnosis of septic shock and is NOT necessary for randomisation 24 hours later. Previous inclusion criteria from 28/02/2019 to 14/08/2020: 1. Male or female aged 18 years or above 2. Being treated on an ICU 3. Septic shock according to internationally accepted definitions* 4. Heart rate =95 bpm (24 hours after start of vasopressor therapy) 5. Receiving vasopressor support to maintain a target blood pressure for =24 hours 6. Are being treated with noradrenaline at a rate = 0.1 mcg/kg/min *Sepsis -3 definitions: 1. Confirmed or suspected infection requiring antibiotic therapy 2. New organ dysfunction, as evidenced by an increase in SOFA score =2 3. A blood lactate >2 mmol/l at any point during shock resuscitation 4. Vasopressor therapy to maintain mean arterial pressure (MAP) =65 mmHg In particular the presence of a blood lactate > 2 mmol/l is only necessary for the diagnosis of septic shock and is NOT necessary for randomisation 24 hours later. Previous inclusion criteria: 1. Male or female aged 18 years or above 2. Being treated on an ICU 3. Septic shock according to internationally accepted definitions* 4. Heart rate =95 bpm (24 hours after start of vasopressor therapy) 5. Receiving vasopressor support with noradrenaline to maintain a target blood pressure for =24 hours 6. Are being treated with noradrenaline at a rate = 0.1 mcg/kg/min *Sepsis -3 definitions: 1. Confirmed or suspected infection requiring antibiotic therapy 2. New organ dysfunction, as evidenced by an increase in SOFA score =2 3. A blood lactate >2 mmol/l at any point during shock resuscitation 4. Vasopressor therapy to maintain mean arterial pressure (MAP) =65 mmHg In particular the presence of a blood lactate > 2 mmol/l is only necessary for the diagnosis of septic shock and is NOT necessary for randomisation 24 hours later
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 14/08/2020: 1. Tachycardia as a result of pain, discomfort from medical devices (including endotracheal tubes), during interventions or other patient distress 2. Any form of vasodilatory shock that is not caused by sepsis 3. Noradrenaline infusion 72 hours after start of vasopressor therapy 5. 55mmHg) 8. Acute severe bronchospasm (due to asthma or COPD) 9. Untreated second or third-degree heart block 10. Untreated phaeochromocytoma 11. Prinzmetal's angina 12. A past history of ischaemic stroke or transient ischaemic attack (TIA) or untreated severe carotid stenosis. 13. Advanced liver disease with Child-Pugh Score of =B. 14. Known sensitivity to beta-blockers 15. Patient/legal representative unwilling to provide written informed consent 16. Known to be pregnant 17. Terminal illness other than septic shock with a life expectancy 72 hours in the current cause of septic shock after start of vasopressor therapy 5. Having pre-existing severe cardiac dysfunction (NYHA grade 4 or more) 6. Having pre-existing severe pulmonary hypertension (mean PA pressures > 55mmHg) 7. Acute severe bronchospasm (due to asthma or COPD) 8. Untreated second or third degree heart block 9. Untreated phaeochromocytoma 10. Prinzmetal's angina 11. A past history of ischaemic stroke or transient ischaemic attack (TIA) or untreated 12. Severe carotid stenosis. 13. Advanced liver disease with Child-Pugh Score of =B. 14. Known sensitivity to beta-blockers 15. Patient/legal representative unwilling to provide written informed consent 16. Known to be pregnant 17. Terminal illness other than septic shock with a life expectancy 72 hours after start of vasopressor therapy 3. Having pre-existing severe cardiac dysfunction (NYHA grade 4 or more) 4. Having pre-existing severe pulmonary hypertension (mean PA pressures > 55mmHg) 5. Acute severe bronchospasm (due to asthma or COPD) 6. Untreated second or third degree heart block 7. Untreated phaeochromocytoma 8. Prinzmetal's angina 9. A past history of ischaemic stroke or transient ischaemic attack (TIA) or untreated severe carotid stenosis. 10. Advanced liver disease with Child-Pugh Score of =B 11. Having been treated with any beta-blocker drug in the seventy two hours prior to screening. 12. Known sensitivity to beta-blockers 13.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Organ failure is measured using the mean SOFA score over the first 14 days from entry to the trial and whilst in ICU. Measurement of the SOFA score will cease if the patient dies or is discharged from the ICU. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 12/11/2019: 1. Mortality is measured using patient records and telephone visits at day 28 and day 90 2. Length of ICU and hospital stay are measured using patient notes up to 90 days 3. Reduction in dose and duration of vasopressor treatment is measured using patient notes for up to 14 days following randomisation Exploratory Outcome Measures: 4. Myocardial dysfunction and inflammation are measured using assays on blood samples taken on days 0, 1, 2, 4, 6 and the End of Noradrenaline Treatment Visit Previous secondary outcome measures: 1. Mortality is measured using patient records and telephone visits at day 28 and day 90 2. Length of ICU and hospital stay are measured using patient notes up to 90 days 3. Individual organ failure-days in 28 day survivors is measured using medical tests (recording SOFA score parameters - oxygenation, renal, hepatic and coagulation function) at day 28 4. Reduction in dose and duration of vasopressor treatment (total doses of adrenaline, dobutamine, phosphodiesterase inhibitors) is measured using patient notes for up to 14 days following randomisation 5. Cardiovascular safety outcomes are measured using hospital notes for the first 14 days Exploratory Outcome Measures: 6. Myocardial dysfunction and inflammation are measured using assays on blood samples taken on days 0, 1, 2, 4, 6 and the End of Noradrenaline Treatment Visit | — |
Countries
England, Northern Ireland, Scotland, United Kingdom
Outcome results
None listed