3児の親さん薬剤師のブログ

とある薬剤師です。感染症治療を考える素材をちょこっと提供。https://note.mu/twin1980。

A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis

NEJMに報告された、リファンピン耐性結核に対するより短期のレジメンのRCT : STREAM

非劣勢 P3。

  • フルオロキノロン系とアミノグリコシド系に感受性を示すリファンピン耐性結核患者を対象
  • 高用量のモキシフロキサシンを含む短期レジメン(9~11 ヵ月)を受ける群
  • The short regimen consisted of moxifloxacin (high-dose), clofazimine, ethambutol, and pyrazinamide administered over a 40-week period, supplemented by kanamycin, isoniazid, and prothionamide in the first 16 weeks
  • 2011 年の WHO ガイドラインに従った長期レジメン(20 ヵ月)を受ける群
  • 主要有効性転帰は 132 週の時点での良好な状態とし,結核菌(Mycobacterium tuberculosis)の培養が 132 週とその前の時点で陰性で,その間に陽性はなく,それ以前に不良な転帰もないことと
  • 非劣性は,10 パーセントポイント以下

 

https://www.nejm.org/doi/full/10.1056/NEJMoa1811867

clinicaltrials.gov

f:id:akinohanayuki:20190407072903j:plain

 感想

 

MDR-TBに対して、短期レジメも同等であったと素晴らしい報告。

ただし、短期レジメンは死亡とQT延長はが気になる結果だったので、慎重にwatchする必要あり。

 

Abstract


BACKGROUND
Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011.

METHODS
We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority.

 

RESULTS
Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group — a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], −7.5 to 9.5) (P=0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, –0.7 percentage points; 95% CI, −10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia’s formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P=0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively.

CONCLUSIONS
In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current Controlled Trials number, ISRCTN78372190; ClinicalTrials.gov number, NCT02409290.)

 

 

あなたも名医! どうするの、結核は!! (Jmed36)

あなたも名医! どうするの、結核は!! (Jmed36)