Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis

Summary

Phase 3 study to evaluate the efficacy and safety of cefepime/nacubactam or aztreonam/nacubactam compared to imipenem/cilastatin in the treatment of complicated urinary tract infections (cUTI) or acute uncomplicated pyelonephritis (AP).

Timeline

Start

2023-05-23

Primary completion

2024-11-22

Completion

2024-11-26

Outcome

Met primary endpoint

paper The primary endpoint was achieved by 176 (82%) of 214, 81 (72%) of 112, and 64 (61%) of 105 patients PMID 42134354 ↗

paper The percentage difference in the success rate versus imipenem-cilastatin was 21·3% (95% CI 10·9 to 32·0) for cefepime-nacubactam (non-inferior and superior), PMID 42134354 ↗

paper and 11·4% (-1·2 to 23·7) for aztreonam-nacubactam (non-inferior). PMID 42134354 ↗

Publications

• Takahashi S, Tateda K, Yanagihara K, Huang H, Doi Y, Yasuda M, Matsumoto K, Sumiya M, Takaya R, Suwada K, Kamiyabu S, Sasagawa Y, Minamida T, Kato S, Kondo K, Naruse T, Mikamo H. Efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam compared with imipenem-cilastatin for complicated urinary tract infection or acute uncomplicated pyelonephritis (Integral-1): a double-blind, randomised phase 3 trial. Lancet. 2026 May 16;407(10542):1929-1940. doi: 10.1016/S0140-6736(26)00596-9.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Aztreonam	Small molecule	2 g	Intravenous
Subject	Cefepime	Small molecule	2 g	Intravenous
Comparator	Cilastatin	Small molecule	1 g	Intravenous
Comparator	IMIPENEM ANHYDROUS	Small molecule	1 g	Intravenous
Subject	nacubactam	Small molecule	1 g	Intravenous

Indications