Trauma Organ Protection Using Artesunate (TOP-ART)
Trial registration number: ISRCTN15731357
Artesunate is a drug that has been in use for many years as the treatment of choice for severe malaria. It has very few adverse effects and can even be used safely by patients with kidney failure or liver dysfunction.
Using experimental (rat) models of severe bleeding, we have discovered that the intravenous injection of small doses of Artesunate (1 to 4.8 mg/kg) upon resuscitation reduces organ failure after trauma haemorrhage. The drug appears to enhance the protection of organs by reducing the body’s excessive inflammatory response to injury and blood loss, and by activating well-known cell-survival pathways.
Having made this exciting discovery in the laboratory, C4TS now want to translate these findings to patients by conducting a Phase 2a clinical trial.
The aim of this trial, ‘Trauma Organ Protection using ARTesunate’ (TOP-ART), is to compare safety and benefit of Artesunate administration in addition to standard treatment in severely-injured bleeding trauma patients.
Study Design
TOP-ART is being conducted as a single centre study at the Royal London Hospital Major Trauma Centre. We will recruit 105 adult trauma patients who will be randomised to receive either:
- Low dose intravenous Artesunate (35 patients)
- High dose intravenous Artesunate (35 patients)
- Placebo (35 patients)
The trial will enrol eligible patients over a 24-month period and determine patient outcomes in-hospital for up to 28 days and mortality at 90 days. The trial started in mid 2017.
A therapeutic agent that reduces the incidence and severity of multiple organ failure could have a major global impact on trauma patient outcomes and their requirements for healthcare utilisation.
Key Documents
The key documents supporting the trial can be downloaded from the links below:
Trial Status
Phase 1, which used a treatment does of 2.4mg/kg (the WHO recommended level for artesunate's current indication) was completed on 20 June 2018. Phase 2 has commenced, and patients are now being treated at a higher dose (4.8mg/kg), which pre-clinical studies suggested could be more efficacious. Patient recruitment is on track.
Contacts
Principal Investigator: Professor Chris Thiemermann
Clinical Trial Manager: Ms Claire Rourke
