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Eravacycline Proves Non-Inferior to Meropenem for the Treatment of cIAI in IGNITE4 Trial

MAY 04, 2018 | KRISTI ROSA
At the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Larry Tsai, MD, Tetraphase Pharmaceutical’s chief medical officer, shared IGNITE4 phase 3 trial results which indicated that eravacycline proved to be non-inferior to meropenem for the treatment of complicated intra-abdominal infections (cIAI).

Eravacycline is a novel, fully-synthetic fluorocycline broad-spectrum antibiotic that has been developed to treat serious, life-threatening multidrug-resistant bacterial infections.

“There are several things that make eravacycline a unique antibiotic,” Patrick Horn, MD, PhD, Tetraphase’s former chief medical officer told Contagion® in a past interview. “One of the biggest is its range of coverage. Even within the multidrug-resistant gram-negative pathogens, it covers most of the known resistance mechanisms.”

IGNITE4 was a global, multi-center, double-blind, phase 3 trial in which investigators set out to assess the use of eravacycline for the treatment of cIAI. A total of 500 patients were enrolled in the trial and were randomized (1:1) to receive either eravacycline (1 mg/kg intravenously (IV) q12h) or meropenem (1g IV q84) for up to 14 days.

The clinical outcome at the test of cure visit (TOC, 28 days after randomization) was the primary efficacy endpoint, according to the abstract of the study.

Out of the 500 participants, 199 (39.8%) had complicated appendicitis, 301 (60.2%) had other diagnoses including complicated cholecystitis (24%), intestinal perforation (7%), and stomach/duodenal perforation (11%). According to the authors, the treatment arms were well-matched.

The investigators cultured baseline isolates from 400 of the patients; these included Escherichia coli (260), Klebsiella spp (62), Acinetobacter spp (12), Pseudomonas aeruginosa (39), enterococci (146), streptococci (152), Staphylococcus aureus (110), and Bacteroides spp (182).

“For the micro-IT population, 7 subjects in each arm were clinical failures at TOC manifested as: persistence of clinical symptoms (Eravacycline=1, Meropenem=3), unplanned surgical procedure (5 each), wound infection (Eravacycline=2, Meropenem=0), and rescue antibiotics (6 each),” the study authors write.

The investigators report no serious adverse events (AEs) associated with eravacycline. However, overall, 37.2% and 30.9% of those receiving eravacycline or meropenem, respectively, reported at least 1 treatment-emergent AE. Furthermore, reactions at the infusion site and gastrointestinal issues were the most common AEs reported in both arms of the trial; however, they occurred in <5% of participants.

The study successfully met its primary efficacy endpoint, which was to demonstrate non-inferiority of eravacycline to meropenem for the treatment of cIAI. Furthermore, the antibiotic was found to be well-tolerated.

“These data support the use of eravacycline for the treatment of cIAI, including infections caused by pathogens resistant to other antibiotics,” the authors conclude.

The thought is that eravacycline can potentially play a key role in the treatment of serious, hard-to-treat hospital infections. When asked what the clinical significance of bringing eravacycline to market is, Tetraphase’s CEO Guy Macdonald told Contagion®, “Recently, the US Centers for Disease Control and Prevention (CDC) noted that antibiotic-resistant infections lead to at least 23,000 deaths each year [and] that number that continues to grow. In highlighting the lack of treatments for these infections, the CDC noted that unless the medical landscape changes, medical procedures and simple procedures that today are routine, may one day become deadly. New therapies for cIAI are needed urgently.”
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