Study into the Reversal of Septic Shock with Landiolol (Beta Blockade)
Research type
Research Study
Full title
STRESS-L: STudy into the REversal of Septic Shock with Landiolol (Beta Blockade)
IRAS ID
213669
Contact name
Tony Whitehouse
Contact email
Sponsor organisation
University Hospitals Birmingham NHS Foundation Trust
Eudract number
2017-001785-14
Duration of Study in the UK
3 years, 8 months, 31 days
Research summary
Septic shock is the most severe form of sepsis. This is a life-threatening condition that arises when the body's response to severe infection causes injury to its own tissues and organs. The mortality from septic shock remains very high (>40% in 3 randomised trials reported in the New England Journal of Medicine in 2014 and >60% with high noradrenaline doses and tachycardia). Despite huge research efforts over the last 20-30 years the survival rate has remained stubbornly unchanged. Outcomes have improved for sepsis in general through earlier recognition and intervention with antibiotics, however once septic shock takes hold, the risk of dying remains very high.
There is growing interest in the use of beta-adrenergic blockade following supportive results in animal and preliminary human studies. Recently, an Italian group (Morelli 2013) used the short-acting beta blocker esmolol to reduce, and then maintain, heart rates of patients with septic shock at between 80-95 beats per minute. The study was not powered for mortality but marked improvements were seen in survival as well as time on vasopressors, and biochemical and functional markers of renal, pulmonary and cardiac function. Their study was relatively small recruiting 154 patients from a single centre. If replicable in larger studies, this represents an unexplored mechanism in sepsis and has important implications for the treatment and outcomes of this high-risk population. A recent review (Chacko 2015) concluded that there was currently insufficient evidence to justify the routine use of beta-blockade in septic shock and further adequately powered multi-centred randomised controlled clinical trials were required. We aim to repeat the Rome study in 340 patients from approximately 35 UK ICUs to see if we can confirm the safety and benefits that were seen.
Summary of study results:
What was the question?
Septic shock (sometimes called blood poisoning) is a life-threatening condition caused by severe infection. In some people, the inflammation that fights the infection goes out of control and results in widespread harm to the patient and failure of normal functioning of vital organs.
The STRESS-L trial aimed to see if using a very short-acting beta-blocker (landiolol) along with standard treatment helps the organs to heal faster in patients with septic shock. The trial also aimed to find the way in which beta blockers work in these patients.
What did we do?
126 adults (74 men, 52 women) who were being treated for septic shock in an Intensive Care Unit in the UK took part in the trial. They were patients who had been treated to correct a low blood pressure with noradrenaline and had a heart rate of more than 95 beats per minute (bpm). Patients were allocated at random to receive either usual (standard) care or usual care plus landiolol. Landiolol is a beta blocker drug which is very short acting and so can control the heart rate very precisely. Patients in the landiolol group received the drug intravenously (IV) as an infusion to bring their heart rate to below 95 bpm timepoints were collected from all participants.
What did we find?
There was no difference in the amount of organ failure between groups but the study was stopped early because there was concern that landiolol was not going to be better than standard care by the end of the trial. More patients died in the landiolol group but this was not statistically significant. The blood tests taken during the study did not show differences between the two groups and so we could not find a way in which landiolol could help to heal patients.
What does this mean?
Our results suggest that the use of landiolol is not likely to be beneficial in patients in ICU with septic shock and a fast heart rate after 24 hours of blood pressure support.
What does this not mean?
STRESS-L only studied very sick patients with fast heart rates on high doses of noradrenaline with established septic shock. There may be times in different patients and circumstances that landiolol is an appropriate treatment.
REC name
East of England - Essex Research Ethics Committee
REC reference
17/EE/0368
Date of REC Opinion
9 Nov 2017
REC opinion
Further Information Favourable Opinion