英国爱丁堡大学Moira Whyte联合东英吉利大学Andrew M. Wilson团队比较了复方新诺明和安慰剂治疗中重度特发性肺纤维化患者的疗效。2020年12月8日，该研究发表在《美国医学会杂志》上。

特发性肺纤维化（IPF）的预后较差，治疗选择有限。 IPF患者的肺微生物群已改变，肺内细菌负担与死亡率有关；先前的研究表明，使用复方新诺明有临床益处。

为了确定复方新诺明治疗中重度IPF患者中的疗效，2015年4月（首次患者就诊）至2019年4月（最后患者随访），研究组在英国39个专业间质性肺病中心进行了一项双盲、安慰剂对照、平行组、随机试验，招募了342例IPF患者，均伴有呼吸困难和肺功能受损。将其随机分组，其中170例接受口服复方新诺明治疗，172例接受匹配的安慰剂治疗，为期12-42个月，所有患者均每日口服5 mg叶酸。主要结局为全因死亡、肺移植或首次非选择性入院时间。

342名参与者的平均年龄为71.3岁，其中13％为女性，共有283名（83％）完成了试验。平均随访时间为1.02年。复方新诺明组和安慰剂组的参与者每人-随访年发生的事件数分别为0.45和0.38起，风险比为1.2。其他事件结局、肺功能或患者报告的结局在统计学上无显著差异。复方新诺明组共发生696起不良反应，其中恶心89起，腹泻52起，呕吐28起，皮疹31起；安慰剂组共发生640起不良反应，其中恶心67起，腹泻84起，呕吐20起，皮疹20起。

研究结果表明，对于中重度IPF患者，与安慰剂相比，口服复方新诺明的治疗并未减少死亡、移植或非选择性住院的综合结局。

附：英文原文

Title: Effect of Co-trimoxazole (Trimethoprim-Sulfamethoxazole) vs Placebo on Death, Lung Transplant, or Hospital Admission in Patients With Moderate and Severe Idiopathic Pulmonary Fibrosis: The EME-TIPAC Randomized Clinical Trial

Author: Andrew M. Wilson, Allan B. Clark, Tony Cahn, Edwin R. Chilvers, William Fraser, Matthew Hammond, David M. Livermore, Toby M. Maher, Helen Parfrey, Ann Marie Swart, Susan Stirling, David R. Thickett, Moira Whyte, on behalf of the EME-TIPAC team

Issue&Volume: 2020/12/08

Abstract:

Importance  Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited treatment options. Patients with IPF have altered lung microbiota, with bacterial burden within the lungs associated with mortality; previous studies have suggested benefit with co-trimoxazole (trimethoprim-sulfamethoxazole).

Objective  To determine the efficacy of co-trimoxazole in patients with moderate and severe IPF.

Design, Setting, and Participants  Double-blind, placebo-controlled, parallel randomized trial of 342 patients with IPF, breathlessness (Medical Research Council dyspnea scale score >1), and impaired lung function (forced vital capacity ≤75% predicted) conducted in 39 UK specialist interstitial lung disease centers between April 2015 (first patient visit) and April 2019 (last patient follow-up).

Interventions  Study participants were randomized to receive 960 mg of oral co-trimoxazole twice daily (n=170) or matched placebo (n=172) for between 12 and 42 months. All patients received 5 mg of folic acid orally once daily.

Main Outcomes and Measures  The primary outcome was time to death (all causes), lung transplant, or first nonelective hospital admission. There were 15 secondary outcomes, including the individual components of the primary end point respiratory-related events, lung function (forced vital capacity and gas transfer), and patient-reported outcomes (Medical Research Council dyspnea scale, 5-level EuroQol 5-dimension questionnaire, cough severity, Leicester Cough Questionnaire, and King’s Brief Interstitial Lung Disease questionnaire scores).

Results  Among 342 individuals who were randomized (mean age, 71.3 years; 46 [13%] women), 283 (83%) completed the trial. The median (interquartile range) duration of follow-up was 1.02 (0.35-1.73) years. Events per person-year of follow-up among participants randomized to the co-trimoxazole and placebo groups were 0.45 (84/186) and 0.38 (80/209), respectively, with a hazard ratio of 1.2 ([95% CI, 0.9-1.6]; P=.32). There were no statistically significant differences in other event outcomes, lung function, or patient-reported outcomes. Patients in the co-trimoxazole group had 696 adverse events (nausea [n=89], diarrhea [n=52], vomiting [n=28], and rash [n=31]) and patients in the placebo group had 640 adverse events (nausea [n=67], diarrhea [n=84], vomiting [n=20], and rash [n=20]).

Conclusions and Relevance  Among patients with moderate or severe IPF, treatment with oral co-trimoxazole did not reduce a composite outcome of time to death, transplant, or nonelective hospitalization compared with placebo.

DOI: 10.1001/jama.2020.22960

Source: https://jamanetwork.com/journals/jama/article-abstract/2773680