Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

A specialist technique used to study drugs has been completed for the first time during an outbreak of Ebola virus disease.

Researcher wearing a mask © Dr Thomas Massaquoi of 34 Military Hospital, Trials Clinician: RAPIDE-TKM trial team

The study published in eBiomedicine was a collaboration of researchers from Sierra Leone and the Universities of Glasgow, Oxford, Cambridge and the Liverpool School of Tropical Medicine. It used pharmacokinetics – the measurement of the change in drug concentration in a person over time – to study an experimental drug called TKM-130803 for the treatment of Ebola virus disease during the 2015 outbreak in Sierra Leone.

Although treatment with TKM-130803 did not appear to improve survival, possibly because the patients presented with advanced disease, the research team were able to use pharmacokinetic analyses to gain important new insights.

In the study, the researchers measured the concentration of the drug over time in patients with Ebola. The scientists looked at the relationship between drug and Ebola virus concentrations and used the data to conduct computer simulations to answer important questions about what would happen if the dose and timing of drug administration were altered.

Significant findings were that the amount of virus (the ‘viral load’) was not significantly different in patients who lived or died, and that the concentration of drug was higher in those who died than in those who survived.

Dr Janet Scott, Clinical Lecturer in Infectious Diseases at the University of Glasgow-MRC Centre for Virus Research, said: “The field team successfully gathered data and samples under extremely difficult conditions, right in the middle of the largest ever outbreak of Ebola Virus Disease in 2015. Rather than focus only on whether we could show that the drug worked or not, we were also able to study how the drug concentrations changed with time in patients. With this we were able to make a mathematical model, and predict what would probably have happened if we had used another dose.

“We had worried, that the dose chosen for this study might have been too low, but this analysis was able to show us that our caution had been justified, and that pushing the dose even higher would probably not have been safe. This reminds us that caution is important, especially when treating these extremely unwell patients.”

Dr Raman Sharma, senior post-doctoral research associate, Liverpool School of Tropical Medicine,  said: “We have been able to show that even with data from very few patients, this kind of research is worth that extra effort, and can yield useful and important results, pushing our understanding of the drug and the dose beyond what can be learnt in the laboratory.”

The laboratory analysis inside the Ebola Treatment Unit was led by Dr Luc Meredith Senior Post Doctoral Scientist, University of Cambridge. He said: “It was difficult to remain accurate and keep the team safe, particularly in the excessive heat of northern Sierra Leone – but this needs to be done if we are to learn everything we can about Ebola and whatever new virus emerges next.”

Professor Peter Horby, Professor of Emerging Infectious Diseases and Global Health, University of Oxford said: “An important lesson is that pharmacokinetic analyses are  possible even in very challenging settings and such analyses can provide important insights. This may be especially valuable in small or very quick outbreaks where there may be too few patients enrolled in trials to provide definitive proof of clinical impact. In such circumstance we can still measure the relationship between drug concentrations and virus concentrations, or other markers of disease progression, to give us an idea if the dose is adequate and drug is having an effect.”

The study, Pharmacokinetics of TKM-130803 in Ebola virus disease in Sierra Leonean: patients showed plasma concentrations which exceeded target levels, with accumulation of drug in patients with most severe disease, is published in eBiomedicine. The work was funded by Wellcome and the EU FP7 project PREPARE.

Similar stories

RECOVERY trial closes recruitment to convalescent plasma treatment for patients hospitalised with COVID-19

@Oxford Research

Convalescent plasma has been widely used as a treatment for COVID-19 but to date there has been no convincing evidence of the effect of convalescent plasma on clinical outcomes in patients admitted to hospital with COVID-19. Recruitment to the convalescent plasma arm of the RECOVERY trial has now closed. The preliminary analysis based on 1873 reported deaths among 10,406 randomised patients shows no significant difference in the primary endpoint of 28-day mortality. Recruitment to all other treatment arms – tocilizumab, aspirin, colchicine, and Regeneron’s antibody cocktail – continues as planned.

Check-list recommended to improve reporting of microscopy methods and results in malaria studies

@Oxford MORU Publication Research

A study to explore the variations of how microscopy methods are reported in published malaria studies has recommended standardised procedures should be implemented for methodological consistency and comparability of clinical trial outcomes.

UK National Health Service begins rollout of Oxford coronavirus vaccine

@Oxford General

The first patients are being vaccinated as part of the UK’s rollout of the Oxford / AstraZeneca coronavirus vaccine, ChAdOx1 nCoV-19, at the Oxford University NHS Hospitals Trust. The Oxford AstraZeneca vaccinations will be delivered at a small number of hospitals for the first few days for surveillance purposes, as is standard practice, before the bulk of supplies are sent to hundreds of GP-led services later in the week.

Receiving and responding to community feedback during health system crises in Kenya

KWTRP Publication Research

The responsiveness of a health system is one of its goals, alongside fairness in financing and outcomes. Listening and responding to the public can make a health system stronger and fairer. However, responsiveness is likely to be undermined, especially for vulnerable and marginal populations, in periods of crises such as disease outbreaks. In the current COVID-19 crisis, there has been more focus on health system control interventions, with minimal consideration of community views. KWTRP colleagues in Kenya consider community engagement and citizens feedback channels, concerns raised by the public and how they were handled, and highlight lessons learned.

Susie Dunachie awarded flagship NIHR career development award

@Oxford Awards & Appointments

Susie Dunachie joins a prestigious group of leading health researchers in the latest cohort of NIHR Global Research Professors. These awards fund research leaders of the future to promote effective translation of research and to strengthen health, public health and care research leadership at the highest academic levels. Research conducted by Global Research Professors directly benefits people in LMICs. A Consultant in Infectious Diseases and Medical Microbiology, Susie works on the development of a vaccine to prevent death from melioidosis in people with type 2 diabetes mellitus in LMICs, and supports vaccine research in Thailand. Congratulations!

RECOVERY trial finds no benefit from azithromycin in patients hospitalised with COVID-19

@Oxford Research

Established in March 2020, the RECOVERY trial tests a range of potential treatments for COVID-19, including azithromycin, a widely used antibiotic that also reduces inflammation. The azithromycin arm of the trial was established to determine whether or not the drug has a meaningful benefit among patients hospitalised with COVID-19. A preliminary analysis shows no significant difference in the primary endpoint of 28-day mortality; there was also no evidence of beneficial effects on the risk of progression to mechanical ventilation or length of hospital stay.