Tropical Projects, 24 The Paddock, Hitchin, UK.
Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), German Centre for Infection Research (DZIF), Bonn-Cologne Site, University Hospital Bonn, Venusberg-Campus 1, 53105, Bonn, Germany.
Parasit Vectors. 2020 Mar 30;13(1):155. doi: 10.1186/s13071-020-04024-2.
As new lymphatic filariasis infections are eliminated through mass chemotherapy, previously affected individuals are left with the sequellae, especially chronic progressive lymphoedema. Currently this is managed by careful attention to limb hygiene to prevent infection. Studies over the past 15 years have suggested that the incorporation of doxycycline treatment may arrest or even reverse progression of lymphoedema. Most of this work has been observational or based on small studies, and if this intervention is effective, studies need to be conducted on a larger scale and under diverse geographical and social conditions before it can be incorporated into treatment policy.
METHODS/DESIGN: The double-blind, placebo-controlled study was designed to investigate the impact of six weeks treatment with doxycycline added to standard limb hygiene on early stage filarial lymphoedema in five sites in Africa and the Indian subcontinent. One site in Cameroon is selected for studying lymphoedema in podoconiosis. Each site was individually powered with the potential to undertake a meta-analysis on completion. Evaluation methods followed those used in Ghana in 2012 with additions resulting from advances in technology. The details of the core protocol and how it was varied to take account of differing situations at each of the sites are provided. The study will enrol up to 1800 patients and will complete in mid-2021.
This paper provides details of what challenges were faced during its development and discusses the issues and how they were resolved. In particular, the reasons for inclusion of new technology and the problems encountered with the supply of drugs for the studies are described in detail. By making these details available, it is hoped that the study protocol will help others interested in improving treatment for filarial lymphoedema in the design of future studies. Trial registration India: Clintrials.gov. NCT02929121 registered 10 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT02929121 Mali: Clintrials.gov. NCT02927496 registered 7 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT0292749 Sri Lanka: Clintrials.gov. NCT02929134 registered 10 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT02929134 Ghana: ISRCTN. 14042737 registered 10 July 2017: https://doi.org/10.1186/ISRCTN14042737 Tanzania: ISRCTN. 65756724 registered 21 July 2017: https://doi.org/10.1186/ISRCTN65756724 Cameroon: ISRCTN. 1181662 registered 25 July 2017: https://doi.org/10.1186/ISRCTN11881662.
随着新的淋巴丝虫病感染通过大规模化疗得以消除，以前受感染的个体留下了后遗症，尤其是慢性进行性淋巴水肿。目前，这种疾病的治疗方法是通过仔细关注肢体卫生来预防感染。过去 15 年的研究表明，加入强力霉素治疗可能会阻止甚至逆转淋巴水肿的进展。这项工作的大部分都是观察性的，或者基于小规模研究，如果这种干预措施有效，需要在更大的范围内进行研究，并在不同的地理和社会条件下进行，然后才能将其纳入治疗政策。
方法/设计：这项双盲、安慰剂对照研究旨在调查在非洲和印度次大陆的五个地点，对强力霉素治疗 6 周对早期丝虫性淋巴水肿的影响。喀麦隆的一个地点被选中用于研究 Podoconiosis 引起的淋巴水肿。每个地点都有潜力在完成后进行单独的荟萃分析。评估方法沿用了 2012 年在加纳使用的方法，并因技术进步而有所增加。提供了核心方案的详细信息以及如何针对每个地点的不同情况进行修改的信息。该研究将招募多达 1800 名患者，并将于 2021 年年中完成。
本文详细介绍了在研究开发过程中所面临的挑战，并讨论了这些问题以及如何解决这些问题。特别是，详细介绍了纳入新技术的原因以及在研究药物供应方面遇到的问题。通过提供这些详细信息，希望研究方案能够帮助其他有兴趣在未来研究中改善淋巴丝虫病治疗的人。
印度： Clintrials.gov。NCT02929121 于 2016 年 10 月 10 日注册：https://clinicaltrials.gov/ct2/show/NCT02929121。马里： Clintrials.gov。NCT02927496 于 2016 年 10 月 7 日注册：https://clinicaltrials.gov/ct2/show/NCT02927496。斯里兰卡： Clintrials.gov。NCT02929134 于 2016 年 10 月 10 日注册：https://clinicaltrials.gov/ct2/show/NCT02929134。加纳： ISRCTN。14042737 于 2017 年 7 月 10 日注册：https://doi.org/10.1186/ISRCTN14042737。坦桑尼亚： ISRCTN。65756724 于 2017 年 7 月 21 日注册：https://doi.org/10.1186/ISRCTN65756724。喀麦隆： ISRCTN。1181662 于 2017 年 7 月 25 日注册：https://doi.org/10.1186/ISRCTN11881662。
