Published: 20 October 2020
The need for new treatments
Sepsis is a life-threatening condition that occurs when the body's own immune system overreacts to an infection which starts to damage its own tissue and organs. It is an illness that can affect people of any age and patients can become critically ill very quickly.
- Before Covid-19 it was the leading cause for admission to an Intensive Care Unit in the UK, accounting for about 30 per cent of all admissions.
- The NHS spends at least £700 million per year treating these patients on Intensive Care Units.
- Despite advances in treatment around 40 per cent of such patients do not survive – more than breast and bowel cancer combined.
Sepsis can cause the patient’s blood pressure to fall dangerously, compromising blood flow to vital organs such as the liver and kidney. Conventionally, adrenaline-like drugs (Catecholamines) are used to support a patient’s blood pressure, but they can have serious side effects including a heart attack.
Levosimendan is a new type of drug that improves the function of the heart in a different manner to the adrenaline-like drugs by opening the patient’s blood vessels. It has been extensively studied in patients with heart failure and is a licensed drug for this group of patients.
In patients with sepsis, around half may develop impaired heart function and associated kidney failure. A number of small studies had suggested that Levosimendan might improve organ function or increase survival rate, but none have been large enough to prove this.
Could Levosimendan be the answer?
The LeoPARDS trial, jointly funded by the NIHR, MRC and Industry partners Tenax Therapeutics, set out to identify whether using Levosimendan in patients with sepsis could reduce multiple organ failure, leading to a better chance of survival for patients.
Patients being treated for sepsis on an Intensive Care Unit, and who had low blood pressure that required the use of adrenaline-like drugs to maintain it, were asked to take part. NIHR Clinical Research Nurses screened and randomised patients so that half of those taking part in the trial were randomly chosen to receive an additional infusion of Levosimendan, whilst the other half received a dummy treatment, or placebo. 516 patients took part in the study from 34 Intensive Care Units across the UK.
The research showed that Levosimendan did not improve organ function or increase survival rate. Patients who received the drug required more adrenaline-like drugs and were therefore also at risk of the serious side effects.
Patients who received Levosimendan were less likely to be successfully weaned from mechanical ventilation, and more likely to have faster heart rates and a higher rate of irregular heart beats than those who received a placebo.
“Small studies had suggested Levosimendan may have a role in sepsis. However, ICU clinicians in the NHS wanted more evidence about its risk/benefit profile before using it widely. The LeoPARDS trial has provided clear answers to help medical teams make the best decisions to manage such critically ill patients.” Professor Anthony Gordon, Chief Investigator, Imperial College London.
Whilst it did not prove effective in helping reduce organ failure and survival of sepsis, the results of the trial are useful for clinicians considering using the drug to treat sepsis patients, helping to reduce unnecessary drug use and the risk of side-effects.
Reducing unnecessary drug use
Reducing unnecessary treatments helps to save precious NHS time and resources. In this case, Levosimendan was not previously included in any UK clinical guidelines, but NHS clinicians were beginning to use it to treat sepsis. The results of the trial are now included in the International Guidelines for Management of Severe Sepsis and Septic Shock 2016. With Levosimendan costing several hundred pounds per day, this trial has saved the NHS a considerable amount of money.
The results of the trial also highlighted the importance of controlling patients' heart rates in sepsis, which may lead to damage of the heart and poor heart function. The biological samples from this trial are now being used to develop a personalised medicine in sepsis platform, as part of an NIHR Research Professorship award. Professor Gordon and his team are now working with colleagues in Birmingham to study the effects of beta-blockers in slowing down patient heart rates in sepsis.
More NIHR research on sepsis
The results of the LeoPARDS trial have been published in the New England Journal of Medicine.
See the LeoPARDS project page for more information on this study.