A randomised trial to assess whether the addition of a beta blocker infusion (landiolol) to standard treatment in patients with septic shock, requiring prolonged (>24 hours) support with high-dose vasopressor agents, improves organ failure (the STRESS-L trial)
- Conditions
- Septic shockInfections and InfestationsInfection/ Other infectious diseases, Inflammatory and Immune System/ Certain disorders involving the immune mechanism
- Registration Number
- ISRCTN12600919
- Lead Sponsor
- niversity Hospitals Birmingham NHS Foundation Trust
- Brief Summary
2021 Protocol article in http://dx.doi.org/10.1136/bmjopen-2020-043194 (added 12/05/2021) 2023 Results article in https://doi.org/10.1001/jama.2023.20134 (added 26/10/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 340
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
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 <0.1mcg/kg/min
4. >72 hours after start of vasopressor therapy
5. <12 hours since noradrenaline to treat a medical condition after than septic shock stopped
6. Having pre-existing severe cardiac dysfunction (NYHA grade 4 or more)
7. Having pre-existing severe pulmonary hypertension (mean PA pressures > 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 < 28 days
18. Participants who have been administered an investigational medicinal product for another research trial in the past 30 days
19. Patients in whom the clinical team feel are about to finish their noradrenaline therapy
20. Receiving extracorporeal membrane oxygenation (ECMO) treatment
Previous exclusion criteria from 12/11/2019 to 14/08/2020:
1. Any form of compensatory tachycardia
2. Any form of vasodilatory shock that is not caused by sepsis
3. Noradrenaline infusion <0.1mcg/kg/min
4. >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 < 28 days
18. Participants who have been administered an investigational medicinal product for
19. Another research trial in the past 30 days
20. Patients in whom the clinical team feel are about to finish their noradrenaline
21. Therapy
22. Decision of withdrawal of care is in place or imminently anticipated
Previous exclusion criteria as of 28/02/2019:
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method