Condition category
Signs and Symptoms
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Plain English Summary

Background and study aims
Septic shock is a condition where blood pressure falls in response to overwhelming infection, resulting in poor blood flow to the kidneys and other vital organs and leading to the failure of these organs. It is a life-threatening condition and requires emergency treatment in an intensive care unit. It is the commonest cause for admission to intensive care in the UK and despite improvements in its treatment around 40% of patients die as a result. It is normal practice for intensive care doctors to attempt to restore a patient's blood pressure to a relatively normal level using adrenaline-like drugs called catecholamines which can improve the function of the heart. However, it is increasingly being recognised that these drugs have important side effects and may even be associated with harm. Levosimendan is a new type of drug that improves the function of the heart in a different manner to the adrenaline-like drugs. It has been extensively studied in patients with heart failure and is a licensed drug for this group of patients in many European countries and elsewhere around the world. Around half of patients with septic shock may develop impaired heart function and associated kidney failure, and levosimendan has been shown to improve this. Its use in septicaemia (blood poisoning) has been studied in both animals and humans, and so far the small patient studies have shown promise, but none have been large enough to assess the effect on important patient-centred outcomes. The aim of this study to investigate whether levosimendan benefits patients with septicaemia by reducing the severity of organ failure.

Who can participate?
Patients aged 18 and over with septicaemia

What does the study involve?
Participants are randomly allocated to be infused with either levosimendan or a placebo (dummy drug) for 24 hours. Organ failure, kidney injury, heart output, duration of mechanical ventilation, and blood oxygen levels are assessed.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
ICU Charing Cross Hospital (UK)

When is the study starting and how long is it expected to run for?
November 2013 to October 2016

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Jonas Lexow

Trial website

Contact information



Primary contact

Mr Jonas Lexow


Contact details

ICU Charing Cross Hospital
Fulham Palace Road
W6 8RF
United Kingdom

Additional identifiers

EudraCT number

2012-005159-18 number

Protocol/serial number


Study information

Scientific title

An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS)



Study hypothesis

In this study we plan to undertake a randomised, controlled trial in a number of intensive care units to investigate whether levosimendan, when added to standard care, can produce important benefits for patients with septicaemia by reducing the severity of organ failure.

Ethics approval

First Medical Reasearch Ethic Committee (MREC), 26/04/2013; Ref: 13/LO/0365

Study design

Randomised; Interventional; Design type: Not specified, Treatment

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use contact details to request a participant information sheet


Topic: Generic Health Relevance and Cross Cutting Themes; Subtopic: Generic Health Relevance (all Subtopics); Disease: Critical Care


1. Levosimendan, 0.05 - 0.2 µg/kg/min infusion for 24 hours
2. Matching placebo, infusion for 24 hours
Follow Up Length: 6 month(s); Study Entry : Single Randomisation only

Intervention type



Not Applicable

Drug names


Primary outcome measures

Mean sequential organ failure assessment (SOFA) score; Timepoint(s): On ICU after randomisation

Secondary outcome measures

1. Acute kidney injury; Timepoint(s): Day 14
2. Cardiac output; Timepoint(s): upto 96 hours
3. Duration of mechanical ventilation; Timepoint(s): In ICU
4. Central venous oxygen saturation (ScvO2); Timepoint(s): upto 96 hours
5. Serum bilirubin; Timepoint(s): In ICU upto day 28

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. The target population includes adult patients (=18 years) who require vasopressor support for the management of sepsis despite fluid resuscitation
2. Inclusion criteria will use the internationally-established consensus definitions of sepsis. In brief, fulfil 2 out of 4 of the criteria of the systemic inflammatory response syndrome (SIRS) due to known or suspected infection within the previous 24 hours. The SIRS criteria are:
2.1. Fever (>38 C) or hypothermia (< 36 C)
2.2. Tachycardia (heart rate > 90 beats per minute)
2.3. Tachypnoea (respiratory rate > 20 breaths per minute or PaCO2 < 4.3 kPa) or need for mechanical ventilation
2.4. Abnormal leukocyte count [> 12,000 cells/mm3, < 4000 cells/mm3, or > 10% immature (band) forms]
3. Hypotension, despite adequate intravenous fluid resuscitation, requiring treatment with a vasopressor infusion (e.g. noradrenaline/adrenaline/vasopressin analogue) for at least four hours and still having an ongoing vasopressor requirement at the time of randomisation.

Target Gender: Male & Female

Participant type


Age group




Target number of participants

Planned Sample Size: 516; UK Sample Size: 516; Description: Randomised 1:1

Participant exclusion criteria

The exclusion criteria are as follows:
1. More than 24 hours since meeting all the inclusion criteria
2. Endstage renal failure at presentation (previously dialysis-dependent)
3. Severe hepatic impairment (Child-Pugh class C)
4. A history of Torsades de Pointes
5. Significant mechanical obstructions affecting ventricular filling or outflow or both
6. Treatment limitation decision in place [e.g. Do not attempt resuscitation (DNAR) or not for ventilation/dialysis]
7. Known or estimated weight of more than135kg
8. Known to be pregnant
9. Previous treatment with levosimendan within 30 days
10. Known hypersensitivity to levosimendan or any of the excipients
11. Known to have received another investigational medicinal product within 30 days or currently in another interventional trial that might interact with the study drug.

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

ICU Charing Cross Hospital
W6 8RF
United Kingdom

Sponsor information


Imperial College of Science, Technology and Medicine (UK)

Sponsor details

International Centre for Circulatory Health
Exhibition Rd
United Kingdom

Sponsor type




Funder type


Funder name

National Institute for Health Research (NIHR) (UK); Grant Codes: 11/14/08

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in:

Publication citations

  1. Protocol

    Orme RM, Perkins GD, McAuley DF, Liu KD, Mason AJ, Morelli A, Singer M, Ashby D, Gordon AC, An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): protocol for a randomized controlled trial., Trials, 2014, 15, 199, doi: 10.1186/1745-6215-15-199.

Additional files

Editorial Notes

17/06/2016: Plain English summary added.