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

NCT03687255 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: AT-301
• Study Type: interventional
• Target: 1,043
• Locations: 18 countries
• Sites: 23

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

Outcome Measures

Primary Outcomes (1)

• Proportion of patients in the Microbiological Modified Intent to Treat (m-MITT) Population who achieve overall treatment success at Test Of Cure (TOC)

  Treatment success is defined as the composite of clinical outcome of Cure and the microbiological outcome of Eradication (\<103 CFU/mL in urine culture).

  7 days after EOT [±2 days] for patients receiving 7 days of treatment and 19 days after randomization [±2 days] for patients receiving more than 7 days of treatment.

Secondary Outcomes (1)

• Proportion of patients in the m-MITT Population with overall treatment success at End of Treatment (EOT)

  7 days for patients with cUTI only and up to 14 days for patients cUTI and blood stream infections

Study Arms (2)

cefepime/AAI101 combination

EXPERIMENTAL

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

Drug: cefepime/AAI101 combination

piperacillin/tazobactam

ACTIVE COMPARATOR

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

Drug: Piperacillin/tazobactam

Interventions

cefepime/AAI101 combination DRUG

cefepime 2 g / AAI101 500 mg

cefepime/AAI101 combination

Piperacillin/tazobactam DRUG

piperacillin 4 GM / tazobactam 500 MG

Also known as: PIP/TAZ

piperacillin/tazobactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients \>18 years of age at the time of signing of informed consent;
• Expectation that the patient's cUTI or AP will require hospitalisation and initial treatment with at least 7 days of intravenous (i.v.) antibiotics;
• Female patients who are no longer of childbearing potential
• 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;
• Male patients, female patients receiving hormone replacement therapy (HRT), and female patients of childbearing potential must agree to use highly effective contraception methods
• 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;
• Clinical signs and/or symptoms of cUTI or AP
• Have a baseline urine culture specimen obtained within 48 hours prior to randomization
• 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.

You may not qualify if:

• 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);
• 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);
• In the opinion of the Investigator, the patient is considered unlikely to survive the approximately 6-week study period;
• Weight \>180 kg;
• Concurrent infection that would interfere with evaluation of response to the study antibiotics;
• 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;
• 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;
• Complicated urinary tract infection (UTI) known at study entry to be caused by pathogens resistant to the study antibiotics;
• Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study;
• Intractable UTI at baseline that the Investigator anticipates would require \>14 days of study drug therapy;
• 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);
• Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter;
• Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy.
• Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination;
• 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,

Sponsors & Collaborators

• Allecra: lead
• Medpace, Inc.: collaborator

Study Sites (24)

St. Josephs Clinical Research

Anaheim, California, 92804, United States

Location

Southbay Pharma Research

Buena Park, California, 90620, United States

Location

Florida Urology Partners

Tampa, Florida, 33615, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercury Street Medical

Butte, Montana, 59701, United States

Location

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

HIGA Dr Ramon Carrillo

Buenos Aires, B1706FWM, Argentina

Location

Brest Regional Hospital

Brest, 224027, Belarus

Location

MHAT Rahila Angelova AD, Pernik

Pernik, 2300, Bulgaria

Location

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

Zagreb, 10000, Croatia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

Unimed Adjara - Kutaisi oncological centre

Kutaisi, 4600, Georgia

Location

Bugat Pal Korhaz

Gyöngyös, 3200, Hungary

Location

Uroklinika, LLC

Riga, LV-1006, Latvia

Location

Republican Siauliai caunty hospital

Šiauliai, 76231, Lithuania

Location

Centro Especializado en Investigación Clínica S.C.

Boca del Río, CP. 94290, Mexico

Location

Clinica Internacional - Sede San Borja

Lima, 15036, Peru

Location

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

Warsaw, 02-507, Poland

Location

Scientific Research Center Eco-Safety

Saint Petersburg, 196143, Russia

Location

Clinical Hospital Center Zvezdara

Belgrade, 11000, Serbia

Location

Interne oddelenie, Nemocnica Malacky, Nemocnicna a.s.

Malacky, 90122, Slovakia

Location

Clinical Projects Research

Worcester, 6850, South Africa

Location

Hospital del Mar, Department of Infectious Disease

Barcelona, 8003, Spain

Location

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

Chernihiv, 14034, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 36194218 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

Cefepime; Piperacillin, Tazobactam Drug Combination

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tazobactam; Penicillanic Acid; Penicillins; Piperacillin; Ampicillin; Penicillin G; Sulfones; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: September 27, 2018
• Study Start: September 24, 2018
• Primary Completion: January 30, 2020
• Study Completion: February 15, 2020
• Last Updated: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1); HU (1); RU (1); ES (1); BE (1); LA (1); CR (1); US (6); PE (1); UA (1); BU (1); SE (1); PL (1); LI (1); ZA (1); GE (1); AR (1); SL (1)