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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03687255
Recruitment Status : Completed
First Posted : September 27, 2018
Last Update Posted : March 10, 2020
Medpace, Inc.
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Urinary Tract Infections Drug: cefepime/AAI101 combination Drug: Piperacillin/tazobactam Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1043 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Study to Evaluate the Efficacy and Safety of Cefepime-AAI101 Compared to Piperacillin/Tazobactam in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis.
Actual Study Start Date : September 24, 2018
Actual Primary Completion Date : January 30, 2020
Actual Study Completion Date : February 15, 2020

Arm Intervention/treatment
Experimental: cefepime/AAI101 combination
Cefepime 2 g in combination with AAI101 500 mg q8h (2 hour infusion)
Drug: cefepime/AAI101 combination
cefepime 2 g / AAI101 500 mg

Active Comparator: piperacillin/tazobactam
Piperacillin 4 g in combination with Tazobactan 500 mg q8h (2 hour infusion)
Drug: Piperacillin/tazobactam
piperacillin 4 GM / tazobactam 500 MG
Other Name: PIP/TAZ

Primary Outcome Measures :
  1. Proportion of patients in the Microbiological Modified Intent to Treat (m-MITT) Population who achieve overall treatment success at Test Of Cure (TOC) [ Time Frame: 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. ]
    Treatment success is defined as the composite of clinical outcome of Cure and the microbiological outcome of Eradication (<103 CFU/mL in urine culture).

Secondary Outcome Measures :
  1. Proportion of patients in the m-MITT Population with overall treatment success at End of Treatment (EOT) [ Time Frame: 7 days for patients with cUTI only and up to 14 days for patients cUTI and blood stream infections ]
    Treatment success is defined as the composite of clinical outcome of Cure and the microbiological outcome of Eradication (<103 CFU/mL in urine culture).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03687255

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Sponsors and Collaborators
Medpace, Inc.
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Responsible Party: Allecra Identifier: NCT03687255    
Other Study ID Numbers: AT-301
First Posted: September 27, 2018    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Communicable Diseases
Urinary Tract Infections
Disease Attributes
Pathologic Processes
Urologic Diseases
Piperacillin, Tazobactam Drug Combination
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action