複方新諾明治療中重度特發性肺纖維化患者不能改善臨床結局
作者：
小柯機器人發布時間：2020/12/10 16:26:32
英國愛丁堡大學Moira Whyte聯合東英吉利大學Andrew M. Wilson團隊比較了複方新諾明和安慰劑治療中重度特發性肺纖維化患者的療效。2020年12月8日，該研究發表在《美國醫學會雜誌》上。
特發性肺纖維化（IPF）的預後較差，治療選擇有限。 IPF患者的肺微生物群已改變，肺內細菌負擔與死亡率有關；先前的研究表明，使用複方新諾明有臨床益處。
為了確定複方新諾明治療中重度IPF患者中的療效，2015年4月（首次患者就診）至2019年4月（最後患者隨訪），研究組在英國39個專業間質性肺病中心進行了一項雙盲、安慰劑對照、平行組、隨機試驗，招募了342例IPF患者，均伴有呼吸困難和肺功能受損。將其隨機分組，其中170例接受口服複方新諾明治療，172例接受匹配的安慰劑治療，為期12-42個月，所有患者均每日口服5 mg葉酸。主要結局為全因死亡、肺移植或首次非選擇性入院時間。
342名參與者的平均年齡為71.3歲，其中13％為女性，共有283名（83％）完成了試驗。平均隨訪時間為1.02年。複方新諾明組和安慰劑組的參與者每人-隨訪年發生的事件數分別為0.45和0.38起，風險比為1.2。其他事件結局、肺功能或患者報告的結局在統計學上無顯著差異。複方新諾明組共發生696起不良反應，其中噁心89起，腹瀉52起，嘔吐28起，皮疹31起；安慰劑組共發生640起不良反應，其中噁心67起，腹瀉84起，嘔吐20起，皮疹20起。
研究結果表明，對於中重度IPF患者，與安慰劑相比，口服複方新諾明的治療並未減少死亡、移植或非選擇性住院的綜合結局。
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