PMID- 25534727
OWN - NLM
STAT- MEDLINE
DCOM- 20151221
LR  - 20231213
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 59
IP  - 3
DP  - 2015 Mar
TI  - Multicenter, randomized clinical trial to compare the safety and efficacy of 
      LFF571 and vancomycin for Clostridium difficile infections.
PG  - 1435-40
LID - 10.1128/AAC.04251-14 [doi]
AB  - Clostridium difficile infection causes serious diarrheal disease. Although 
      several drugs are available for treatment, including vancomycin, recurrences 
      remain a problem. LFF571 is a semisynthetic thiopeptide with potency against C. 
      difficile in vitro. In this phase 2 exploratory study, we compared the safety and 
      efficacy (based on a noninferiority analysis) of LFF571 to those of vancomycin 
      used in adults with primary episodes or first recurrences of moderate C. 
      difficile infection. Patients were randomized to receive 200 mg of LFF571 or 125 
      mg of vancomycin four times daily for 10 days. The primary endpoint was the 
      proportion of clinical cures at the end of therapy in the per-protocol 
      population. Secondary endpoints included clinical cures at the end of therapy in 
      the modified intent-to-treat (mITT) population, the time to diarrhea resolution, 
      and the recurrence rate. Seventy-two patients were randomized, with 46 assigned 
      to receive LFF571. Based on the protocol-specified definition, the rate of 
      clinical cure for LFF571 (90.6%) was noninferior to that of vancomycin (78.3%). 
      The 30-day sustained cure rates for LFF571 and vancomycin were 56.7% and 65.0%, 
      respectively, in the per-protocol population and 58.7% and 60.0%, respectively, 
      in the modified intent-to-treat population. Using toxin-confirmed cases only, the 
      recurrence rates were lower for LFF571 (19% versus 25% for vancomycin in the 
      per-protocol population). LFF571 was generally safe and well tolerated. The 
      incidence of adverse events (AEs) was higher for LFF571 (76.1% versus 69.2% for 
      vancomycin), although more AEs in the vancomycin group were suspected to be 
      related to the study drug (38.5% versus 32.6% for LFF571). One patient receiving 
      LFF571 discontinued the study due to an AE. (This study has been registered at 
      ClinicalTrials.gov under registration no. NCT01232595.).
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Mullane, Kathleen
AU  - Mullane K
AD  - The University of Chicago Medicine, Section of Infectious Diseases and Global 
      Health, Chicago, Illinois, USA.
FAU - Lee, Christine
AU  - Lee C
AD  - St. Joseph's Healthcare Hamilton, Hamilton Regional Laboratory Medicine Program, 
      McMaster University, Department of Pathology and Molecular Medicine, Hamilton, 
      Ontario, Canada.
FAU - Bressler, Adam
AU  - Bressler A
AD  - Infectious Disease Specialists of Atlanta, Decatur, Georgia, USA.
FAU - Buitrago, Martha
AU  - Buitrago M
AD  - Idaho Falls Infectious Disease, Idaho Falls, Idaho, USA.
FAU - Weiss, Karl
AU  - Weiss K
AD  - Universite de Montreal, Departement de Microbiologie et d'Infectiologie, Hopital 
      Maisonneuve-Rosemont, Montreal, Quebec, Canada.
FAU - Dabovic, Kristina
AU  - Dabovic K
AD  - Novartis Institutes for BioMedical Research, Infectious Disease Area, East 
      Hanover, New Jersey, USA.
FAU - Praestgaard, Jens
AU  - Praestgaard J
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
FAU - Leeds, Jennifer A
AU  - Leeds JA
AD  - Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, 
      California, USA.
FAU - Blais, Johanne
AU  - Blais J
AD  - Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, 
      California, USA.
FAU - Pertel, Peter
AU  - Pertel P
AD  - Novartis Institutes for BioMedical Research, Infectious Disease Area, Cambridge, 
      Massachusetts, USA peter.pertel@novartis.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01232595
GR  - UL1 TR000430/TR/NCATS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141222
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - W7AUL2R95Z (LFF571)
RN  - 0 (Thiazoles)
RN  - 6Q205EH1VU (Vancomycin)
SB  - IM
CIN - Antimicrob Agents Chemother. 59:1441.
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Bacterial Agents/adverse effects/*therapeutic use
MH  - Clostridioides difficile/*drug effects
MH  - Clostridium Infections/*drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Thiazoles/adverse effects/*therapeutic use
MH  - Vancomycin/adverse effects/*therapeutic use
PMC - PMC4325808
EDAT- 2014/12/24 06:00
MHDA- 2015/12/22 06:00
PMCR- 2015/09/01
CRDT- 2014/12/24 06:00
PHST- 2014/12/24 06:00 [entrez]
PHST- 2014/12/24 06:00 [pubmed]
PHST- 2015/12/22 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - AAC.04251-14 [pii]
AID - 04251-14 [pii]
AID - 10.1128/AAC.04251-14 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2015 Mar;59(3):1435-40. doi: 10.1128/AAC.04251-14. 
      Epub 2014 Dec 22.