Safety and Efficacy Study of Cefepime-AAI101 in the Treatment of Complicated Urinary Tract Infections

NCT ID: NCT03687255

Last Updated: 2020-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1043 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-24
• Study Completion Date: 2020-02-15

Brief Summary

Multi-center, randomized, double-blind, non-inferiority study of cefepime 2 g/AAI101 500 mg combination compared to piperacillin 4 g/tazobactam 500 mg in a population of adult patients with cUTI or AP. The study will be conducted in approximately 115 sites located in the EU, the US, Central, South America and South Africa.

Conditions

Urinary Tract Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

cefepime/AAI101 combination

Cefepime 2 g in combination with AAI101 500 mg q8h (2 hour infusion)

Group Type: EXPERIMENTAL

cefepime/AAI101 combination

Intervention Type: DRUG

cefepime 2 g / AAI101 500 mg

piperacillin/tazobactam

Piperacillin 4 g in combination with Tazobactan 500 mg q8h (2 hour infusion)

Group Type: ACTIVE_COMPARATOR

Piperacillin/tazobactam

Intervention Type: DRUG

piperacillin 4 GM / tazobactam 500 MG

Interventions

cefepime/AAI101 combination

cefepime 2 g / AAI101 500 mg

Intervention Type: DRUG

Piperacillin/tazobactam

piperacillin 4 GM / tazobactam 500 MG

Intervention Type: DRUG

Other Intervention Names

PIP/TAZ

Eligibility Criteria

Inclusion Criteria

1. Male or female patients >18 years of age at the time of signing of informed consent;

2. Expectation that the patient's cUTI or AP will require hospitalisation and initial treatment with at least 7 days of intravenous (i.v.) antibiotics;

3. Female patients who are no longer of childbearing potential

4. Female patients of childbearing potential must have a negative urine and/or serum pregnancy test (serum β-human chorionic gonadotropin) within 1 day prior to study entry;

5. Male patients, female patients receiving hormone replacement therapy (HRT), and female patients of childbearing potential must agree to use highly effective contraception methods

6. Pyuria, defined as: a. White blood cell count >10 cells/mm3 in unspun urine or ≥10 cells/high power field in spun urine sediment; or b. Urinalysis/dipstick analysis positive for leukocyte esterase;

7. Clinical signs and/or symptoms of cUTI or AP

8. Have a baseline urine culture specimen obtained within 48 hours prior to randomization

9. Expectation, in the judgment of the Investigator, that any implanted urinary instrumentation (e.g., nephrostomy tubes, ureteric stents, etc.) will be surgically removed or replaced before or within 24 hours after randomisation, unless removal or replacement is considered unsafe or contraindicated.

Exclusion Criteria

1. Known urine culture with Gram-positive primary pathogen at ≥105 colony-forming units (CFU)/mL (not contaminant) or suspected Gram-positive pathogen by Gram staining (Note: Gram staining is optional);

2. History of significant hypersensitivity or allergic reaction to cefepime, piperacillin/tazobactam, any of the excipients used in the respective formulations, any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams), or any beta-lactamase inhibitors (e.g., tazobactam, sulbactam, or clavulanic acid);

3. In the opinion of the Investigator, the patient is considered unlikely to survive the approximately 6-week study period;

4. Weight >180 kg;

5. Concurrent infection that would interfere with evaluation of response to the study antibiotics;

6. Need for or receipt of concomitant systemic antimicrobial agents after signing of informed consent, in addition to those designated in the study-treatment groups, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis;

7. Receipt of potentially effective systemic antibacterial therapy for a continuous duration of > 24 hours during the previous 72 hours before the study-qualifying baseline urine is obtained;

8. Complicated urinary tract infection (UTI) known at study entry to be caused by pathogens resistant to the study antibiotics;

9. Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study;

10. Intractable UTI at baseline that the Investigator anticipates would require >14 days of study drug therapy;

11. Complete, permanent obstruction of the urinary tract that is not anticipated to be medically or surgically relieved during i.v. study therapy and before End of Treatment (EOT);

12. Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter;

13. Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy.

14. Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination;

15. Impairment of renal function with estimated glomerular filtration rate <30 mL/min/1.73 m2 calculated by the 4-variable Modification of Diet in Renal Disease study equation,

16. Urinary tract surgery within 7 days prior to randomisation or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy prior to EOT);

17. Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of study data;

18. Any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure and respiratory failure;

19. Presence of sepsis, producing life-threatening organ dysfunction

20. A QT interval corrected using Fridericia's formula >450 msec;

21. Immunocompromising condition, including known history of acquired immune deficiency syndrome or known recent CD4 count <200/mm3, hematological malignancy, or bone marrow transplantation; or immunosuppressive therapy including cancer chemotherapy, medications for prevention of organ transplantation rejection, or the administration of corticosteroids ≥20 mg of prednisone or equivalent per day administered continuously for >14 days prior to randomisation;

22. One or more of the following laboratory abnormalities in baseline specimens obtained at Screening: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or total bilirubin level >3 × upper limit of normal, or current clinically significant liver disease, including any form of known liver cirrhosis;

23. One or more of the following laboratory abnormalities at Screening: platelet count <50,000/μL, absolute neutrophil count <1,000/mm3, or hemoglobin <8 g/dL;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medpace, Inc.

INDUSTRY

Sponsor Role: collaborator

Allecra

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

St. Josephs Clinical Research

Anaheim, California, United States

Southbay Pharma Research

Buena Park, California, United States

Florida Urology Partners

Tampa, Florida, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercury Street Medical

Butte, Montana, United States

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States

HIGA Dr Ramon Carrillo

Buenos Aires, , Argentina

Brest Regional Hospital

Brest, , Belarus

MHAT Rahila Angelova AD, Pernik

Pernik, , Bulgaria

University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" Department for general infectious diseases

Zagreb, , Croatia

Tartu University Hospital

Tartu, , Estonia

Unimed Adjara - Kutaisi oncological centre

Kutaisi, , Georgia

Bugat Pal Korhaz

Gyöngyös, , Hungary

Uroklinika, LLC

Riga, , Latvia

Republican Siauliai caunty hospital

Šiauliai, , Lithuania

Centro Especializado en Investigación Clínica S.C.

Boca del Río, , Mexico

Clinica Internacional - Sede San Borja

Lima, , Peru

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie, Klinika Chorob Wewnetrznych, Nefrologii i Transplantologii

Warsaw, , Poland

Scientific Research Center Eco-Safety

Saint Petersburg, , Russia

Clinical Hospital Center Zvezdara

Belgrade, , Serbia

Interne oddelenie, Nemocnica Malacky, Nemocnicna a.s.

Malacky, , Slovakia

Clinical Projects Research

Worcester, , South Africa

Hospital del Mar, Department of Infectious Disease

Barcelona, , Spain

Chernihiv City Hospital #2 of Chernihiv City Council, department of Urology

Chernihiv, , Ukraine

Countries

United States; Argentina; Belarus; Bulgaria; Croatia; Estonia; Georgia; Hungary; Latvia; Lithuania; Mexico; Peru; Poland; Russia; Serbia; Slovakia; South Africa; Spain; Ukraine

References

Kaye KS, Belley A, Barth P, Lahlou O, Knechtle P, Motta P, Velicitat P. Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial. JAMA. 2022 Oct 4;328(13):1304-1314. doi: 10.1001/jama.2022.17034.

Reference Type: DERIVED

PMID: 36194218 (View on PubMed)

Other Identifiers

AT-301

Identifier Type: -

Identifier Source: org_study_id