Lancet

Is gepotidacin as effective as nitrofurantoin in uncomplicated UTI in females?

March 4, 2024

Gepotidacin was non-inferior to nitrofurantoin in EAGLE-2 and EAGLE-3 trials—and superior to nitrofurantoin in EAGLE-3. Diarrhea was the most common side effect in both studies. Given its novel mechanism of action, the drug may hold potential against drug-resistant infections.

• Gepotidacin is a novel oral bactericidal triazaacenaphthylene antibiotic with activity against common uropathogens. It inhibits bacterial DNA replication by acting on a specific binding site to inhibit 2 different type II topoisomerase enzymes.
• EAGLE-2 and EAGLE-3 are phase 3 randomized double-blind, non-inferiority trials conducted at 219 sites. Trial participants (>1,500 for each trial) included non-pregnant females ages 12 years or older with 2 or more symptoms (dysuria, frequency, urgency, lower abdominal pain) plus urinary nitrite, pyuria, or both. Patients were randomly assigned to gepotidacin 1,500 mg twice daily or nitrofurantoin 100 mg twice daily, both for 5 days.
• Primary endpoint was therapeutic success or failure at test-of-cure on day 10-13 in patients who received at least 1 dose of antibiotics. Success was defined as complete symptom resolution plus uropathogen reduction.
• After a prospectively agreed-upon interim analysis, both studies were stopped for efficacy. At that time point, therapeutic success was achieved in 51% of 320 patients assigned gepotidacin vs. 47% of 287 patients assigned nitrofurantoin in EAGLE-2, and 59% of 277 patients assigned gepotidacin vs. 44% of 264 patients assigned nitrofurantoin in EAGLE-3.
• The most common adverse event with gepotidacin was diarrhea, seen in 14% of 766 patients in EAGLE-2 and 18% in EAGLE-3. The most common adverse event with nitrofurantoin was nausea at 4% in both EAGLE-2 and EAGLE-3. No fatal or life-threatening events occurred.

Source:

Wagenlehner F, et al. (2024, February 24). Lancet. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. https://pubmed.ncbi.nlm.nih.gov/38342126/