akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study

The Lancet Infectious Diseases

Published: April 28, 2017

 

Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30235-9/fulltext

 

 

 

P

USA and Canada

Eligible participants had C difficile infection (defined as more than three unformed bowel movements or more than 200 mL of unformed stool in rectal collection devices 24 h before randomisation) and a positive local diagnostic test for C difficileinfection (detection of either a toxigenic strain by nucleic acid amplification tests or free toxin in stool by enzyme immunoassay).

 

f:id:akinohanayuki:20170501121701g:plain

 

E

oral ridinilazole (200 mg every 12 h) for 10 days.

n=36

 

C

 oral vancomycin (125 mg every 6 h) for 10 days.

n=33

 

O

ridinilazole group vs vancomycin group

・clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004)

adverse event  82% (41 of 50) vs 80% (40 of 50) 

 

T

phase 2

randomised, double-blind, active-controlled

non-inferiority study. 

 

f:id:akinohanayuki:20170501120333g:plain

 

 

感想

 

非劣勢試験ですが、CDIの武器になりそうです。

 

副作用も同等。しかし、適応人数少なく、注視する必要あり。

施設は、アメリカとカナダのみ。

サンプルサイズを満たしていない。

 

Introductionが良い復習になります。

 

"Three antibiotics are available for treatment of C difficile infection: metronidazole, vancomycin, and fidaxomicin. Metronidazole is only recommended for treatment of mild-to-moderate episodes and has been shown to be inferior to vancomycin. Both metronidazole and vancomycin are associated with high rates of recurrence due to disruption of the normal microbiota during therapy. Fidaxomicin is non-inferior to vancomycin with respect to clinical response at the end of treatment but superior with regard to sustained clinical response up to 25 days after cessation of treatment.7, 8However, when compared with vancomycin, fidaxomicin does not improve sustained clinical responses against BI/NAP1/027 strains.7, 8 These observations underscore the need for safe and effective alternatives that do not negatively affect the normal gut microbiota, thereby potentially facilitating prevention of recurrent C difficile infection."

 

なお Ridinilazole とは

"Ridinilazole (formerly known as SMT19969) is an antimicrobial restricted to the gastrointestinal tract. In-vitro studies have shown its high inhibitory activity against C difficile and minimal activity against both Gram-positive and Gram-negative aerobic and anaerobic intestinal microorganisms"

 

副作用は、このサイズではなんとも言えないが、悪くなさそう。

"We coded adverse events using the Medical Dictionary for Regulatory Activities (MedDRA; version 17.0)"

f:id:akinohanayuki:20170501120436g:plain

 

限界

私は、3番目がとても問題だと思います。

 

  • First, only 21 of the 33 sites recruited participants for the study. Although 14 sites recruited three or more participants, most of the recruitment (approximately 70%) was done across eight sites.
  • Second, although study participants were reasonably representative of patients with C difficile infection, they were slightly younger and had milder disease.
  • Third, the power calculation of the study was based on the assumption of 100 participants in the primary analysis population. However, although the primary analysis only included 69 participants, the study still met the primary endpoint, establishing non-inferiority and also showing statistical superiority at the prespecified 10% level.
  • Fourth, recurrence was only monitored for 30 days after the end of treatment. Although this follow-up accords with similar phase 2 and phase 3 clinical trials, future studies should consider longer follow-up periods.
  • Finally, 31 participants were not included in the primary analysis population because of a negative free toxin assay. This probably reflects, in part, the suboptimal sensitivity of free toxin assays resulting in false negative results, and poor specificity of molecular assays for detection of C difficile infection resulting in the potential for enrolment of colonised rather than infected participants. However, the rigour with which the modified ITT population was defined mitigates this limitation and supports the study's primary analysis and results.

 

 

その他、期待されているCDI治療オプション

 


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