Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial

Abstract

Astellas Pharma, Inc.

The use of faecal microbiota transplant as treatment for recurrent or refractoryClostridium difficileinfection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

“…There is also some evidence that pulsed/tapered dosing of vancomycin and fidaxomicin (including pulsed fidaxomicin65) results in fewer recurrences than with standard dosing of these agents66 67 (although this finding has not been replicated in all studies68). Pre-planned subgroup analysis of patients with severe CDI in a randomised trial demonstrated a significantly lower recurrence rate when treated with fidaxomicin (13.0%, n=12/92) than when treated with vancomycin (26.6%, n=29/209)63; this finding was replicated in another RCT, with 8.3% (n=4/48) and 32.6% (n=14/43) experiencing a recurrence, respectively 69.…”

Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections

“…Additionally, the extended‐pulsed fidaxomicin treatment resulted in a lower recurrence at 90 days (6%) compared with the vancomycin treatment (19%) ( P = 0.00073, odds ratio 0.29 [95% CI: 0.14–0.60]). This study showed that the extended‐pulsed fidaxomicin treatment resulted in a higher rate of clinical cure for the patients as a whole, with reduced recurrence . However, this study was not powered to look directly at this treatment for patients starting with recurrent CDI, and the study also showed that extended‐pulsed fidaxomicin treatment may be inferior for severe CDI.…”

“…This study showed that the extended-pulsed fidaxomicin treatment resulted in a higher rate of clinical cure for the patients as a whole, with reduced recurrence. 34 However, this study was not powered to look directly at this treatment for patients starting with recurrent CDI, and the study also showed that extendedpulsed fidaxomicin treatment may be inferior for severe CDI. Finally, the study did not compare standard fidaxomicin therapy or extended-pulsed vancomycin therapy to the extended-pulsed fidaxomicin.…”

“…This diagram reviews the recommended treatment approaches for primary and recurrent CDI, depending on disease severity based on the 2018 IDSA/SHEA guidelines. Additionally, there is some evidence for fidaxomicin in place of rifaximin as a chaser for recurrent CDI and the EXTEND trial did show evidence for using extended‐pulsed fidaxomicin for primary CDI; however, this is not currently reflected in the guidelines …”

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spaish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR)

“…With vancomycin tapering, these regimens typically include a 10-to 14-day course of oral vancomycin at a dose of 125 mg four times per day, followed by a tapering dose over two weeks, followed by "pulsed" dosing with 125 mg once every two or three days for two to eight weeks [223,245] The other alternative, is a regime of extended-pulsed fidaxomicin: 200 mg oral tablets, twice daily on days 1-5, then once daily on alternate days on days 7-25. This strategy has been compared with standard vancomycin, demonstrating superiority of fidaxomicin regarding sustained cure of CDI and lower rates of recurrence [246]. role in the improvement of the CDI diagnosis by processing unformed stool specimens from patients older than 2 years, independently of the request by the clinicians.…”