Azithromycin vs. Placebo for the Clinical Outcome in <i>Campylobacter concisus</i> Diarrhoea in Adults: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

Campylobacter concisus has been associated with prolonged mild diarrhoea, but investigations regarding the efficacy of antimicrobial treatment have not been reported previously. We initiated a phase 3, single-centre, randomized, double-blinded, placebo-controlled study comparing the efficacy of 500 mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days. If symptoms persisted at day ten, the patient was offered cross-over study treatment of three days and another ten-day follow-up period. The primary efficacy endpoint was the clinical response, defined as time to cessation of diarrhoea (<3 stools/day or reversal of accompanying symptoms). Our estimated sample size was 100 patients. We investigated a total of 10,036 diarrheic stool samples from 7,089 adult patients. Five-hundred and eighty-eight C. concisus positive patients were assessed for eligibility, of which 559 were excluded prior to randomization. The three main reasons for exclusion were duration of diarrhoea longer than 21 days (n = 124), previous antibiotic treatment (n = 113), and co-pathogens in stools (n = 87). Therefore, 24 patients completed the trial with either azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16–19). One person in the azithromycin group and four from the placebo group chose to continue with crossover medication after the initial ten-day period. In the azithromycin group, there was a mean of seven days (95% CI: 5–9) to clinical cure and for the placebo group it was ten days (95% CI: 6–14) (OR—3 (95% CI: -7–1). We observed no differences in all examined outcomes between azithromycin treatment and placebo. However, due to unforeseen recruitment difficulties we did not reach our estimated sample size of 100 patients and statistical power to conclude on an effect of azithromycin treatment was not obtained. Trial Registration: Clinicaltrials.gov identifier: NCT01531218.简洁弯曲杆菌（Campylobacter concisus）与迁延性轻症腹泻相关，但此前尚无关于其抗菌治疗有效性的研究报道。本研究启动了一项3期、单中心、随机双盲安慰剂对照试验，针对成人简洁弯曲杆菌腹泻患者，比较每日1次、每次500mg阿奇霉素与每日1次、每次500mg安慰剂（疗程3天）的治疗效果，随访周期为10天。若患者在第10天时症状仍持续，则为其提供3天的交叉研究治疗，并再进行10天的随访。本研究的主要疗效终点为临床应答，定义为腹泻停止时间（每日排便<3次或伴随症状缓解）。 本研究预计纳入100例患者。我们共对7089名成人患者的10036份腹泻粪便样本进行了检测。共有588例简洁弯曲杆菌检测阳性的患者接受入组资格评估，其中559例在随机分组前被排除。排除的主要原因有三项：腹泻病程超过21天（124例）、既往接受过抗菌药物治疗（113例）以及粪便中检测到共感染病原体（87例）。因此最终共有24例患者完成试验，其中阿奇霉素组12例，安慰剂组12例。两组患者均表现为迁延性轻症腹泻，平均病程为18天（95%置信区间：16~19天）。阿奇霉素组有1例、安慰剂组有4例患者在初始10天随访结束后选择接受交叉治疗。阿奇霉素组的临床治愈平均时间为7天（95%置信区间：5~9天），安慰剂组为10天（95%置信区间：6~14天）（比值比OR=3，95%置信区间：-7~1）。我们未观察到阿奇霉素治疗与安慰剂在所有检测结局指标上存在差异。但由于不可预见的招募困难，本研究未达到预计的100例样本量，因此未获得可用于推断阿奇霉素治疗效果的统计效力。 试验注册：Clinicaltrials.gov注册号：NCT01531218。