Condition category
Injury, Occupational Diseases, Poisoning
Date applied
25/08/2015
Date assigned
28/08/2015
Last edited
30/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Major trauma accounts for a significant number of deaths worldwide, and is one of the most frequent causes of death in people under the age of 40. A large number of these deaths are caused by massive blood loss (haemorrhage). Low blood pressure due to blood loss puts extreme pressure on vital organs such as the heart and brain, as they are not receiving enough oxygen. Without correct treatment, this eventually leads to multiple organ failure (MOF).
Development of MOF occurs early (within two days of admission) and is related to an increase in hospital-acquired infections and even death. There is currently no specific treatment which is used to protect against MOF after traumatic haemorrhage however. Artesunate is a drug that has been used for many years as the treatment of choice for severe malaria. It has very few adverse effects and can even be used safely for patients suffering with liver or kidney disease. Laboratory experiments using animals have shown that this drug can actually reduce the risk of organ failure after haemorrhage, as it enhances the protection of organs within the body. This study aims to test the safety and effectiveness of the use of Artesunate in patients with severe trauma and blood loss.

Who can participate?
Adult trauma patients who are actively bleeding as the result of traumatic injury.

What does the study involve?
Due to the urgent/emergency nature of the intervention subjects are recruited within 4 hours of their injury and within 2 hours of admission to the Emergency Department. All participants receive emergency care in accordance with local guidelines for traumatic haemorrhage.
Patients are randomly allocated into one of three study groups, receiving either low dose Artesunate (2.4mg/kg), high dose Artesunate (4.8mg/kg) or placebo (inactive medication). Artesunate is given intravenously (though a vein) because the critical condition of the patients means that it is not an option to take the drug orally. Each participant is given the drug, and then remain in the study for 28 days or until they are discharged from hospital. A scoring system known as the Sequential Organ Failure Score (SOFA) is used throughout this period, in order to track the rate of organ failure in the patients.

What are the possible benefits and risks of participating?
The potential benefits of Artesunate in reducing multiple organ failure outweigh the risk of adverse events associated with the medication. Artesunate has been extensively used in the treatment of both child and adult malaria, including use in critically ill patients. As patients will receive all other clinically indicated treatments, there is no risk of ineffective therapy by administration of the study treatment.

Where is the study run from?
The Royal London Hospital (UK)

When is the study starting and how long is it expected to run for?
April 2015 to March 2018

Who is funding the study?
Wellcome Trust (HICF-R7-405) (UK)

Who is the main contact?
Dr Simon Eaglestone (Public)
s.eaglestone@qmul.ac.uk

Trial website

http://www.c4ts.qmul.ac.uk/organ-failure--protection/top-art

Contact information

Type

Scientific

Primary contact

Ms Claire Rourke

ORCID ID

Contact details

Ward 12D
The Royal London Hospital
Barts Health NHS Trust
Whitechapel
London
E1 1BB
United Kingdom
+44 20 3594 0731
claire.rourke@bartshealth.nhs.uk

Additional identifiers

EudraCT number

2015-000301-40

ClinicalTrials.gov number

Protocol/serial number

REDA 009531 / 1.0

Study information

Scientific title

A randomised, blinded placebo-controlled Phase 2a study to evaluate the safety and efficacy of Artesunate treatment in severely injured trauma patients with traumatic haemorrhage.

Acronym

TOP-ART

Study hypothesis

The aim of this study is to determine whether treatment with Artesunate improves the outcome in severely injured subjects with trauma haemorrhage.

Ethics approval

London - City & East Research Ethics Committee, 11/03/2016, ref: 16/LO/003

Study design

Single-centre randomized placebo-controlled parallel group study with a sequential group-dosing regimen (adaptive design).

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Multiple organ failure following traumatic haemorrhage.

Intervention

The trial Intervention arm will be split into two stages:
The first stage will be randomised 2:1 low dose intervention (2.4mg/kg) versus placebo.
The second stage will be randomised 2:1 high dose intervention (4.8mg/kg) versus placebo.
As patients will receive all other clinically indicated treatments, there is no risk of ineffective therapy by administration of the trial treatment.

Intervention type

Drug

Phase

Phase II

Drug names

Artesunate

Primary outcome measures

Sequential Organ Failure Score (SOFA) at 48 hours

Secondary outcome measures

1. Maximum Sequential Organ Failure Score (SOFA) over 7 days
2. Total length of hospital stay
3. Total number of days on organ support (as measured by CTCOFR score)
4. Total length of critical care stay
5. Number of ventilator free days
6. Incidence of acute lung injury (as measured by Lung Injury Score)
7. Incidence of acute kidney injury (as measured by RIFLE score)
8. Incidence of infection
9. Mortality (measured at discharge, after 28 days and after 90 days)

Overall trial start date

01/04/2015

Overall trial end date

31/03/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adult trauma patients (16 years and above).
2. Activation of the local massive haemorrhage protocol
3. Patients with active, ongoing haemorrhage
4. Agreement for participation is provided on behalf of incapacitated patients by Personal Consultee or Nominated Consultee (i.e. trauma team leader)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

105

Participant exclusion criteria

1. Time of admission more than 2 hours after the time of injury
2. Time of drug administration not attainable within 4 hours of injury
3. Subject not expected to survive more than 48 hours
4. Evidence of severe traumatic brain injury (GCS 3 at scene)
5. Known pregnancy
6. Suspected non-haemorrhagic cause of shock
7. Massive haemorrhage protocol activation more than one hour after arrival
8. Concurrent participation in another Clinical Trial of an IMP
9. Breastfeeding females
10. Known allergy to Artesunate

Recruitment start date

01/01/2016

Recruitment end date

31/12/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Royal London Hospital
Barts Health NHS Trust Whitechapel Road
London
E1 1BB
United Kingdom

Sponsor information

Organisation

Queen Mary University of London

Sponsor details

Joint Research & Management Office
QM Innovation Building
5 Walden Street
Whitechapel
London
E1 2EF
United Kingdom
+44 20 7882 7260
sponsorsresp@bartshealth.nhs.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Wellcome Trust Grant Number: 101012

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Results and Publications

Publication and dissemination plan

We intend to present the trial findings in the scientific literature and at medical/scientific conferences. For more wider dissemination, we shall update the Centre’s website (http://www.c4ts.qmul.ac.uk/) to share our findings and circulate an article in the Centre’s newsletter (http://issuu.com/centrefortraumasciences/docs) that is available from the website and posted out to our public followers via our Twitter feed (@CommsC4TS)

Intention to publish date

31/03/2019

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

30/03/2016: The study contact has been updated from Dr Simon Eaglestone to Ms Claire Rourke. 29/03/2016: Ethics approval information added.