Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial

@article{Mesu2018OralFF,
  title={Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial},
  author={Victor Kande Betu Ku Mesu and Wilfried Mutombo Kalonji and Cl{\'e}lia Bardonneau and Olaf Valverde Mordt and Severine Blesson and François Simon and Sophie Delhomme and Sonja C Bernhard and Willy Kuziena and Jean-Pierre Fina Lubaki and Steven Lumeya Vuvu and Pathou Nganzobo Ngima and H{\'e}l{\`e}ne Mahenzi Mbembo and M{\'e}dard Ilunga and Augustin Kasongo Bonama and Josu{\'e} Amici Heradi and Jean Louis Lumaliza Solomo and Guylain Mandula and Lewis Kaninda Badibabi and Francis Regongbenga Dama and Papy Kavunga Lukula and Digas Ngolo Tete and Crispin Lumbala and Bruno Scherrer and Nathalie Strub-Wourgaft and Antoine Tarral},
  journal={The Lancet},
  year={2018},
  volume={391},
  pages={144-154}
}

Figures and Tables from this paper

Fexinidazole in human African trypanosomiasis: a profile of its use
TLDR
In clinical trials, fexinidazole was associated with high rates of treatment success in both stage 1 and 2 g-HAT, with its efficacy in late stage 2 g- HAT being noninferior to that of the standard of oral nifurtimox-intravenous eflornithine combination therapy (NECT).
Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo
TLDR
It is found that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern.
Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo
TLDR
It is found that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern.
Chemotherapy for second‐stage human African trypanosomiasis: drugs in use
TLDR
Oral treatment with fexinidazole is much easier to administer than conventional treatment, but deaths and relapse appear to be more common, however, the advantages or an oral option are considerable, in terms of convenience, avoiding hospitalisation and multiple intravenous infusions, thus increasing adherence.
Modelling the impact of fexinidazole use on human African trypanosomiasis transmission in the Democratic Republic of Congo
TLDR
It is found that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern.
Innovative Partnerships for the Elimination of Human African Trypanosomiasis and the Development of Fexinidazole
TLDR
The long-standing collaboration between the WHO, Sanofi and the Drugs for Neglected Diseases initiative was instrumental for achieving the control and treatment development goals in HAT, whilst at the same time ensuring that efforts were led by national authorities and control programs to leave a legacy of highly trained healthcare workers and improved research and health infrastructure.
Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: Report from a field study
TLDR
NECT treatment administered under field conditions was effective and sufficiently well tolerated, no major concern arose for children or pregnant or breastfeeding women, and patients with a previous HAT treatment history had the same response as those who were naïve.
Efficacy and Toxicity of Fexinidazole and Nifurtimox Plus Eflornithine in the Treatment of African Trypanosomiasis: A Systematic Review
TLDR
Compared to older therapies, fexinidazole and NECT are more effective and safer than eflornithine and melarsoprol monotherapy.
...
...

References

SHOWING 1-10 OF 21 REFERENCES
In-Hospital Safety in Field Conditions of Nifurtimox Eflornithine Combination Therapy (NECT) for T. b. gambiense Sleeping Sickness
TLDR
In field conditions and in a wider population, including children, NECT displayed a similar tolerability profile to that described in more stringent clinical trial conditions, and long term efficacy will be confirmed after 24 months follow-up.
Fexinidazole – A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness
TLDR
Fexinidazole is shown to be a short-course, safe and effective oral treatment curing both acute and chronic HAT and that could be implemented at the primary health care level and the results of the preclinical pharmacological and safety studies indicate that fexinidrazole is a safe andeffective oral drug candidate with no untoward effects that would preclude evaluation in man.
Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II).
TLDR
The effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense is demonstrated in a noncontrolled, multinational drug-utilization study.
Antitrypanosomal Activity of Fexinidazole, a New Oral Nitroimidazole Drug Candidate for Treatment of Sleeping Sickness
TLDR
In vitro and in vivo antitrypanosomal activities of fexinidazole and its two principal metabolites provide evidence that the compound has the potential to be an effective oral treatment for both the T. b.
Epidemiology of human African trypanosomiasis
TLDR
Sustainable elimination of the gambiense HAT, defined as the interruption of the transmission of the disease, was considered as a feasible target for 2030, since rhodesiense H AT is a zoonosis, where the animal reservoir plays a key role, and the interruptionOf the disease’s transmission is not deemed feasible.
Determination of an Optimal Dosing Regimen for Fexinidazole, a Novel Oral Drug for the Treatment of Human African Trypanosomiasis: First-in-Human Studies
TLDR
These studies show that fexinidazole can be safely assessed in patients as a potential oral cure for both stages of HAT.
The Human African Trypanosomiasis Control and Surveillance Programme of the World Health Organization 2000–2009: The Way Forward
TLDR
The World Health Organization (WHO) Expert Committee on HAT Control and Surveillance held in 1995, in consideration of the huge uncertainties between the reported cases and the factual field situation, estimated that the true number of cases was at least 10 times more than reported.
Human African trypanosomiasis in the Democratic Republic of the Congo: disease distribution and risk
TLDR
The progressive decrease in HAT cases reported since 2000 in DRC is likely to reflect a real decline in disease incidence, and the ongoing integration of HAT control and surveillance into the health system is to be closely monitored and evaluated.
...
...