The TOP-ART Study: Trauma Organ Protection - Artesunate
| ISRCTN | ISRCTN15731357 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15731357 |
| EudraCT/CTIS number | 2015-000301-40 |
| Secondary identifying numbers | REDA 009531 / 1.0 |
- Submission date
- 25/08/2015
- Registration date
- 28/08/2015
- Last edited
- 10/05/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Injury, Occupational Diseases, Poisoning
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 September 2019
Who is funding the study?
Wellcome Trust (HICF-R7-405) (UK)
Who is the main contact?
Ms Claire Rourke (Public)
c.rourke@qmul.ac.uk
Contact information
Scientific
Ward 12D
The Royal London Hospital
Barts Health NHS Trust
Whitechapel
London
E1 1BB
United Kingdom
| Phone | +44 20 3594 0731 |
|---|---|
| claire.rourke@bartshealth.nhs.uk |
Study information
| 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 |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet. |
| 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. |
| Study 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(s) | London - City & East Research Ethics Committee, 11/03/2016, ref: 16/LO/003 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Artesunate |
| Primary outcome measure | 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 study start date | 01/04/2015 |
| Overall study end date | 21/09/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 105 |
| 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 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 | 21/03/2017 |
| Recruitment end date | 21/03/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Whitechapel Road
London
E1 1BB
United Kingdom
Sponsor information
University/education
Joint Research & Management Office
QM Innovation Building
5 Walden Street
Whitechapel
London
E1 2EF
England
United Kingdom
| Phone | +44 20 7882 7260 |
|---|---|
| sponsorsresp@bartshealth.nhs.uk | |
"ROR" |
https://ror.org/026zzn846 |
Funders
Funder type
Charity
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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) |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 10/05/2021 | No | No |
Editorial Notes
10/05/2021: Added total final enrolment number and added link to Basic results (scientific).
24/01/2018: The following changes were made:
1. Recruitment start date was changed from 01/01/2016 to 21/03/2017.
2. Recruitment end date was changed from 31/12/2017 to 21/03/2019.
3. Overall trial end date was changed from 31/03/2018 to 21/09/2019.
4. Intention to publish date was changed from 31/03/2019 to 31/12/2019.
30/03/2016: The study contact has been updated from Dr Simon Eaglestone to Ms Claire Rourke.
29/03/2016: Ethics approval information added.
