利福平+克拉霉素与利福平+链霉素治疗局限性布鲁里溃疡的疗效比较，这一成果由荷兰格罗宁根大学医学中心Tjip S van der Werf经过不懈努力取得。相关论文于2020年3月12日发表在《柳叶刀》杂志上。

布鲁里溃疡是一种由溃疡分枝杆菌感染引起的易被忽视的热带病，它损害皮肤和皮下组织，在非洲中西部和澳大利亚最为普遍。每日口服利福平10 mg/kg加肌内注射链霉素15 mg/kg，连续8周（RS8），是标准的抗菌疗法，非常有效，但链霉素注射很疼并可能有害。

研究组进行了一项开放标签、非劣效性、随机、多中心、3期临床试验，招募年龄超过5岁、病变直径不超过10厘米的参与者，比较每日口服10 mg/kg利福平和15 mg/kg克拉霉素全效缓释药，连续8周（RC8）和RS8方案治疗早期局限性布鲁里溃疡的疗效和耐受性。

2013年1月1日至2017年12月31日，研究组招募了310名参与者，中位年龄为14岁，女性占52%。其中297例经PCR证实为布鲁里溃疡，随机分组后，151名患者（51%）接受RS8治疗，146名患者（49%）接受口服RC8治疗。

52周后，RS8组的治愈率为95%，RC8组的治愈率为96%，差异不显著，表明RC8治疗的病变愈合率并不逊于RS8治疗。

RS8组中治疗相关的不良事件发生率为13%，RC8组为7%。大多数不良事件为1-2级，但RS8组中有1名（1%）患者出现严重的耳毒性并在6周后终止治疗。没有患者需要手术，每组各有2名患者接受了植皮。

综上，完全口服的RC8方案治疗早期局限性布鲁里溃疡的疗效并不逊于RS8，且不良事件较少。

附：英文原文

Title: Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial

Author: Richard O Phillips, Jérme Robert, Kabiru Mohamed Abass, William Thompson, Fred Stephen Sarfo, Tuah Wilson, Godfred Sarpong, Thierry Gateau, Annick Chauty, Raymond Omollo, Michael Ochieng Otieno, Thaddaeus W Egondi, Edwin O Ampadu, Didier Agossadou, Estelle Marion, Line Ganlonon, Mark Wansbrough-Jones, Jacques Grosset, John M Macdonald, Terry Treadwell, Paul Saunderson, Albert Paintsil, Linda Lehman, Michael Frimpong, Nanaa Francisca Sarpong, Raoul Saizonou, Alexandre Tiendrebeogo, Sally-Ann Ohene, Ymkje Stienstra, Kingsley B Asiedu, Tjip S van der Werf, Samuel Osei Mireku, Justice Abotsi, Joseph Ken Adu Poku, Richard Asamoah-Frimpong, Bright Osei-Wusu, Edward Sarpong, Beatrice Konadu, Ernest Opoku, Mark Forson, Mathias Ndogyele, Elizabeth Ofori, Felicity Aboagye, Thomas Berko, George Amofa, Anastasia Nsiah, Joyce Mensah-Bonsu, Joseph Ofori Nyarko, Yaw Ampem Amoako, Elliot Koranteng Tannor, Justice Boakye-Appiah, Aloysius Dzibordzi Loglo, Mabel Sarpong-Duah, Bernadette Agbavor, Marie Franoise Ardent, Arnaud Yamadjako, Naomi Adanmado Gersande, Ambroise Adeye, Martial Kindjinou, Akpolan, Maxime Kiki, Espoir Sodjinou, Clémence Guegnard, Sandor-Adrian Klis, Kristien Velding, Till Omansen, David Ofori-Adjei, Sarah Eyangoh, Alan Knell, William Faber

Issue&Volume: 2020-03-12

Abstract: BackgroundBuruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions.MethodsWe did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437.FindingsBetween Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10–29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, 0·5% (–5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1–2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts.InterpretationFully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer.

DOI: 10.1016/S0140-6736(20)30047-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30047-7/fulltext