ADAPT-PO
Trial question
Is tebipenem pivoxil hydrobromide noninferior to ertapenem in patients with complicated UTI?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
58.0% female
42.0% male
N = 868
868 patients (505 female, 363 male)
Inclusion criteria: adult patients with complicated UTI or acute pyelonephritis
Key exclusion criteria: confirmed or suspected infection with a carbapenem-resistant pathogen; receipt of > 1 dose of a short-acting antibiotic within 72 hours before randomization; CrCl ≤ 30 mL/min; severe hepatic impairment;
Interventions
N=449 tebipenem pivoxil hydrobromide (oral dose of 600 mg every 8 hours for 7-10 days or 14 days in bacteremia)
N=419 ertapenem (intravenous dose of 1g every 24 hours for 7 to 10 days or 14 days in bacteremia)
Primary outcome
Composite outcome of clinical cure and microbiologic response at test-of-cure visit
58.8
61.6
61.6 %
46.2 %
30.8 %
15.4 %
0.0 %
Tebipenem pivoxil hydrobromide
Ertapenem
Difference not exceeding
nonferiority margin ✓
Difference not exceeding nonferiority margin in composite outcome of clinical cure and microbiologic response at the test-of-cure visit (58.8% vs. 61.6%; ARD -3.3, 95% CI -9.7 to 3.2)
Secondary outcomes
No significant difference in clinical cure at the test-of-cure visit (93.1% vs. 93.6%; ARD -0.6, 95% CI -4 to 2.8)
No significant difference in microbiologic response at the test-of-cure visit (59.5% vs. 63.5%; ARD -4.5, 95% CI -10.8 to 1.9)
Significant increase in composite outcome of clinical cure and microbiologic response at the end-of-treatment visit (97.3% vs. 94.5%; AD 2.8%, 95% CI 0.1 to 5.7)
Safety outcomes
No significant difference in adverse events.
Conclusion
In adult patients with complicated UTI or acute pyelonephritis, tebipenem pivoxil hydrobromide was noninferior to ertapenem with respect to the composite outcome of clinical cure and microbiologic response at the test-of-cure visit.
Reference
Paul B Eckburg, Lori Muir, Ian A Critchley et al. Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection. N Engl J Med. 2022 Apr 7;386(14):1327-1338.
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