Department of Medicine, University of Chicago, Illinois.
UCLA Medical Center, Los Angeles, California.
Clin Infect Dis. 2019 Jan 7;68(2):196-203. doi: 10.1093/cid/ciy484.
Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients.
In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as "prophylaxis failure" to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure.
Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], P = .278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], P = .0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients.
While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients.
NCT01691248.
艰难梭菌相关性腹泻（CDAD）在造血干细胞移植（HSCT）期间很常见，与发病率和死亡率增加有关。我们评估了 fidaxomicin 预防 HSCT 患者 CDAD 的效果。
在这项双盲研究中，接受氟喹诺酮预防的 HSCT 患者根据移植类型（自体/异基因）分层，随机接受每日一次口服 fidaxomicin（200mg）或匹配的安慰剂。剂量在开始预处理或氟喹诺酮预防后 2 天内开始，并持续到中性粒细胞植入后 7 天或氟喹诺酮预防/临床指示的抗菌药物完成后 40 天。主要终点是研究药物后 30 天内 CDAD 的发生率。主要终点分析将确认的 CDAD、接受 CDAD 有效药物（任何适应证）和 CDAD 评估缺失（任何原因，包括死亡）视为失败；这种综合分析称为“预防失败”，以与预先指定的敏感性分析区分开来，后者仅将确认的 CDAD（通过毒素免疫测定或核酸扩增试验）视为失败。
在纳入的 611 名患者中，有 600 名患者接受了治疗和分析。接受 fidaxomicin 和安慰剂的患者预防失败的比例相似（28.6% vs 30.8%；差异 2.2%[-5.1，9.5]，P =.278）。然而，大多数失败是由于非 CDAD 事件引起的。与安慰剂组相比， fidaxomicin 组确认的 CDAD 发生率较低（4.3% vs 10.7%；差异 6.4%[2.2，10.6]，P =.0014）。接受 fidaxomicin 的患者中有 15.0%发生药物相关不良事件，而接受安慰剂的患者中有 20.0%发生药物相关不良事件。
尽管在主要分析中两组之间未显示出差异，但敏感性分析的结果表明， fidaxomicin 显著降低了 HSCT 受者 CDAD 的发生率。
NCT01691248。
