Shorter treatment may be possible with higher rifampicin doses

An interview with prof. dr. Martin Boeree

A considerably higher dose of the anti-tuberculosis drug rifampicin has been found to be safe according to a recent publication by PanACEA. Higher dosing of rifampicin may lead to a shorter / more efficacious treatment for tuberculosis with less resistance development. With this finding PanACEA researchers complete a decade-long search for the right dosing of rifampicin.

One of the few effective drugs against tuberculosis is rifampicin. Even after fifty years, this remains one of the few anti-tuberculosis drugs that penetrates all parts of the body, including those hard-to-reach areas where the tubercle bacillus resides. Yet all this time, patients have been receiving too low a dosage, of only 10 milligrams per kilogram of body weight.

“A higher dose was too expensive at the time of introduction, people were afraid that the drug would be toxic, and in 95 percent of cases the dose was sufficiently effective,” says Boeree. “That’s why the maximum tolerated dose was never examined. And yet if the dosage is too low, you encourage resistance development in the remaining five percent.”

With this recent PanACEA publication, the search for the maximum dose of rifampicin is now complete. “We now know that at 50 milligrams per kilo, patients suffer from a kind of general malaise. But a dose of 40 milligrams per kilo does not produce severe side effects.” says Boeree.

Whether a higher dose of rifampicin can actually lead to a shorter treatment duration and less resistance is difficult to say on the basis of their research at this point of time. PanACEA will therefore begin follow-up research this summer to determine the actual outcome of their new treatment strategy. “If we know how many patients have recurrent tuberculosis after a year, and we compare this to a control group, we can make a prediction of how well this new regimen may work,” says Boeree.

“We think that a large proportion of patients will not need six months of rifampicin if we give it at a higher dose,” Boeree says. “It’s quite possible that three months is enough.” If that turns out to be the case, he says, it will have a very big impact in the treatment of tuberculosis worldwide. “The shorter the treatment, the higher the adherence and the lower the resistance. With this study, we can increase the effectiveness of this crucial drug.”


This study is part of the EDCTP2 programme supported by the European Union (grant number TRIA2015-1102-PanACEA).

Can Calculus Help Tuberculosis Treatment?

The St Andrews group’s most recent paper has been published as a perspective piece in the International Journal of Tuberculosis and Lung Disease.The collaboration between the Schools of Medicine, Applied Mathematics and Computer Science provides an overview of the different types of model that can be applied to tuberculosis clinical trials.  Importantly, it provides a new insight on mechanistic models that can explore the interaction between pathogens, immune samples and the local environment including antibiotic concentrations.  Tuberculosis is still one of the top 10 causes of death worldwide, this approach could allow patient level simulations and, ultimately, open the prospect of conducting a virtual clinical trial and help us choose between potential new regimens to test.

Community engagement workshop

In the afternoon of 20th of February a ninety minutes interactive workshop on community engagement was held. The inspiring Erica Sanga, Community Engagement Coordinator at NIMR Mwanza, Tanzania, led the workshop.

During this workshop, participants from different sites shared their experiences and challenges on community engagement activities. Participants discussed their best practices for successful engagement of community stakeholders in SimpliciTB and plans to extend engagement to other (new) sites under the PanACEA Consortium with peer-to-peer guidance and training.

Special emphasis was put on engagement of study participants, their families, and other key community stakeholders, already early in the research process. This also includes improving research literacy and dialogue about the trial with key stakeholders at all levels.

SimpliciTB General Assembly F2F

Delegates from all of our collaborators in SimpliciTB TB travelled from across the world to attend the annual face to face General Assembly (GA) meeting in Mbeya, Tanzania. Trial progress was reported, with a focus on recruitment and medical monitoring. An important development was the launch of the Capacity Development programme that allows members of the consortium to bid for funds to develop sites across Africa, for training and for innovative seed-corn projects.

The GA also decided to add Uganda Case Western Reserve University Research Collaboration (Uganda) and Kibong’oto Infectious Disease Hospital (Tanzania) to the consortium.

Dr Erica Sanga from the National Institute Medical Research, Mwanza Medical Research Centre (NIMR-MMRC) presented and facilitated an interactive workshop on Community Engagement and Good Participatory Practices in TB Trials (GPP-TB). Engaging the community who suffer the effects of tuberculosis is very important for the consortium and this workshop helped to give everyone the tools necessary to reach out to local communities and communicate the true nature of the disease.

PanACEA Annual Meeting 2020

For the 10th annual face to face meeting the PanACEA consortium came together in Mbeya, Tanzania, on 19-20 February 2020. This year our partner Mbeya Medical Research Centre (NIMR MMRC) hosted the event. The warm hospitality and great organisation of the team made for a very positive meeting environment.

We were off to a great start with a number of workshops held before the meeting by our so called Expertise Cores. Patrick Phillips and Molly (Xue) Gong from the Statistics Core led workshops for statisticians and non-statisticians alike. The Biomarkers Core had a full program of presentations about ongoing MBLA research, discussions on treatment response biomarkers and new plans for biomarkers data analysis and modelling. Robert Hunt from the Microbiology Core gave a hands-on workshop with troubleshooting and sharing good practice.

The Annual Meeting was opened on Wednesday by the Honourable Deputy Minister Dr. Faustine Ndugulile of the Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDGEC), together with Dr. Nyanda Ntinginya, director of NIMR MMRC, Prof. Yunus Mgaya, director of NIMR, Dr. Deodatus, chairman of the NIMR council and Martin Boeree Coordinator of PanACEA. Another guest of honour at the meeting was Dr. Christian Lienhardt, chair of the Scientific Advisory Board of PanACEA.

The first day the consortium updated eachother on project activities and progress. The BTZ043 trial is steadily enrolling; preparations for the SUDOCU trial are progressing; and the operationalization of the PHENORIF trial has started. The Expertise Cores each gave an extensive update on their progress as well. We ended the day with discussion about the current and future PanACEA scientific program.

The second day was dedicated to research projects not or only indirectly related to PanACEA. Some of the clinical trial sites showed impressive scientific and clinical development since joining PanACEA. This was confirmed by the results of a recent questionnaire about capacity development and leadership that Stellah Mpagama and Nyanda Ntinginya conducted and presented.




PanACEA General Assembly

Monday 9th of December the PanACEA General Assembly (GA) met again for its quarterly assembly to report and discuss the progress of the project.

The first phase of the BTZ043 trial has started at the end of November at UCTLI and TASK Applied Science. Preparations for the SUDOCU and PHENORIF trials are progressing.

Next time, the GA will meet face-to-face at the Annual Meeting in Mbeya, Tanzania on 18th and 19th of February 2020. On this occasion Investigator’s meetings will be held for the BTZ043, SUDOCU and PHENORIF trials. In addition, several of the Expertise Cores are organizing workshops for capacity development purposes. The Cores will present updates about other planned activities at the Annual Meeting.

Press Release

The new drug substance BTZ043 is being tested on patients for the first time in a Phase II study performed by the PanACEA consortium. The trial is carried out in Cape Town, South Africa at TASK Applied Science Clinical Research Centre and the University of Cape Town Lung Institute (UCTLI).

The study is funded by the German Federal Ministry of Education and Research (BMBF) and the European and Developing Countries Clinical Trials Partnership (EDCTP).

BTZ043 was discovered at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena. Since 2014, the new chemical entity has been developed in a consortium of scientists from the Leibniz-HKI and the Tropical In-stitute at the Hospital of the LMU Munich within the framework of the German Center for Infection Research (DZIF).

“Following the promising results of the Phase I study in Germany, we see a great chance that the good tolerability of BTZ043 will be confirmed in the treatment of tuberculosis patients. We are confident that we will also see good results in the first efficacy data.” Says Professor Michael Hoelscher, who is leading the Phase II study. If BTZ043 proves to be safe and effective in the current study, this would be a major step in the development of a new drug.

More information:
LMU press release
Clinical trial registration
About BTZ043

PanACEA adds SUDOCU and PHENORIF trials to portfolio

We are pleased to announce that our consortium has added two trials to its portfolio. The SUDOCU and PHENORIF trials replace the Q203 study that was initially planned in the Grant Agreement. The trials will take place in South Africa and Tanzania in 2020.

Having established the maximum tolerated dose of rifampicin in the HIGHRIF trial, the purpose of the PHENORIF study is to further investigate the interaction potential of the higher dosages with a so-called metabolic phenotyping design. This method is a new concept in the PanACEA trial portfolio.

The objective of the SUDOCU trial is to identify the optimal dose of sutezolid in order to advance it into the novel STEPIIC design of PanACEA in which several combinations regimens are evaluated.

Maximum tolerated dose of rifampicin identified

The PanACEA HIGHRIF trial that started in the first phase of PanACEA has continued in the current programme and has succesfully come to an end. The maximum tolerated dose of rifampicin was identified at 40mg/kg. Martin Boeree recently presented the results at The 50th Union World Conference on Lung Health in Hyderabad, India. The publication will follow soon.

Dr. Francis Mhimbira

Dr. Francis Mhimbira is an epidemiologist and a senior research scientist at Ifakara Health Institute (IHI, He joined IHI since 2012 working with a TB research group conducting TB epidemiological, diagnostic and clinical trials (drugs and vaccines). He has experience in conducting phase II and phase III TB drug clinical trials. He is currently leading the preparation and conduct of PanACEA related studies at Ifakara Health Institute. Dr. Francis has other research interests which include implementation studies on TB case finding and diagnostic studies.

Dr. Francis received his medical degree from University of Dar es Salaam, Tanzania, a Masters’ degree in Epidemiology from University of Melbourne, Australia and a PhD in Epidemiology from University of Basel, Switzerland.