1. Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence
- Author
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Johnson, Stuart, Gerding, Dale N, Li, Xue, Reda, Domenic J, Donskey, Curtis J, Gupta, Kalpana, Goetz, Matthew Bidwell, Climo, Michael W, Gordin, Fred M, Ringer, Robert, Johnson, Neil, Johnson, Michelle, Calais, Lawrence A, Goldberg, Alexa M, Ge, Ling, and Haegerich, Tamara
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Emerging Infectious Diseases ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Clinical Research ,Digestive Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Anti-Bacterial Agents ,COVID-19 ,Clostridioides difficile ,Clostridium Infections ,Diarrhea ,Fidaxomicin ,Humans ,Recurrence ,Treatment Outcome ,Vancomycin ,C ,difficile ,Clinical trial ,Study design ,Clinical treatment ,Veterans ,C. difficile ,Medical and Health Sciences ,General Clinical Medicine ,Public Health ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundAlthough many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences). Therefore, a rigorous RCT of sufficient size was designed to determine the optimal treatment among three antibiotic regimens in current practice for treatment of pauci-rCDI.MethodsVA Cooperative Studies Program (CSP) #596 is a prospective, double-blind, multi-center clinical trial of veteran patients with pauci-rCDI comparing fidaxomicin (FDX) 200 mg twice daily for 10 days and vancomycin (VAN) 125 mg four times daily for 10 days followed by a 3-week vancomycin taper and pulse (VAN-T/P) regimen to a standard course of VAN 125 mg four times daily for 10 days. The primary endpoint is sustained clinical response at day 59, with sustained response measured as a diarrhea composite outcome (D-COM) that includes symptom resolution during treatment (before day 10) without recurrence of diarrhea or other clinically important outcomes through day 59.DiscussionCSP study 596 is designed to compare three current antibiotic treatments for recurrent CDI that are in clinical practice, but which lack high-quality evidence to support strong guideline recommendations. The design of the study which included a pilot phase initiated at six sites with expansion to 24 sites is described along with protocol modifications based on early trial experience and clinical realities including the COVID-19 pandemic.Trial registrationThis study is registered with clinicaltrials.gov (Identifier: NCT02667418).
- Published
- 2022