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Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Complicated UTI in Adults

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: NCT03357614
Recruitment Status : Completed
First Posted : November 30, 2017
Results First Posted : December 29, 2020
Last Update Posted : December 29, 2020
Information provided by (Responsible Party):
Iterum Therapeutics, International Limited

Brief Summary:
This is a prospective, phase 3, randomized, multicenter, double-blind, double-dummy study to compare the efficacy and safety of sulopenem followed by sulopenem-etzadroxil/probenecid versus ertapenem followed by ciprofloxacin for the treatment of complicated urinary tract infections (cUTI) in adults.

Condition or disease Intervention/treatment Phase
Complicated Urinary Tract Infections Drug: Sulopenem Drug: Sulopenem-Etzadroxil/Probenecid Drug: Ertapenem Drug: Ciprofloxacin Drug: Amoxicillin-clavulanate Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1395 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective, Phase 3, Randomized, Multi-center, Double-blind, Double-dummy Study of Efficacy, Tolerability & Safety of Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Treatment of cUTI in Adults
Actual Study Start Date : September 18, 2018
Actual Primary Completion Date : December 14, 2019
Actual Study Completion Date : December 14, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Sulopenem
Sulopenem 1000 mg IV once daily for a minimum of 5 days, followed by sulopenem-etzadroxil/probenecid 500 mg PO twice daily to complete 7-10 total days of treatment
Drug: Sulopenem
Antibiotic therapy for complicated UTI

Drug: Sulopenem-Etzadroxil/Probenecid
Antibiotic therapy for complicated UTI

Active Comparator: Ertapenem
Ertapenem 1000 mg IV once daily for a minimum of 5 days, followed by ciprofloxacin 500 mg PO twice daily or amoxicillin-clavulanate 500 mg PO twice daily to complete 7-10 total days of treatment
Drug: Ertapenem
Antibiotic therapy for complicated UTI
Other Name: Invanz

Drug: Ciprofloxacin
Antibiotic therapy for complicated UTI
Other Name: Cipro

Drug: Amoxicillin-clavulanate
Antibiotic therapy for complicated UTI
Other Name: Augmentin

Primary Outcome Measures :
  1. Percentage of Participants With Overall Success [ Time Frame: Day 21 +/- 1 day ]
    Clinical success is defined as complete resolution of cUTI symptoms present at study entry and no new cUTI symptoms; microbiologic success is defined as eradication of the bacterial pathogen found at study entry (reduced to <1000 CFU/mL)

Secondary Outcome Measures :
  1. Percentage of Participants With Microbiologic Success [ Time Frame: Day 21 +/- 1 day ]
    Microbiologic success is defined as demonstrating <1000 CFU/mL of the baseline urpathogen by quantitative urine culture

Information from the National Library of Medicine

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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. Adults ≥18 years of age with more than 24 hours of urinary symptoms attributable to a UTI
  2. Able to provide informed consent
  3. Clinically documented pyelonephritis or complicated urinary tract infection:

    1. Pyelonephritis with normal anatomy
    2. Complicated UTI as defined by one or more of the following factors:

    i. The presence of an indwelling catheter ii. >100 mL of residual urine after voiding iii. Neurogenic bladder iv. Obstructive uropathy due to nephrolithiasis, tumor or fibrosis v. Azotemia due to intrinsic renal disease vi. Urinary retention in men possibly due to benign prostatic hypertrophy vii. Surgically modified or abnormal urinary tract anatomy

  4. At least two of the following signs or symptoms:

    1. Rigors, chills or fever/hypothermia
    2. Flank pain or pelvic pain
    3. Nausea or vomiting
    4. Dysuria, urinary frequency or urinary urgency
    5. Costovertebral angle tenderness on physical examination
  5. A mid-stream urine specimen with:

    1. a dipstick analysis positive for nitrite AND
    2. evidence of pyuria as defined by either: i. a dipstick analysis positive for leukocyte esterase AND/OR ii. at least 10 white blood cells per cubic millimeter on microscopic analysis of unspun urine AND/OR iii. White blood cell count ≥10 cells/high-powered field in urine sediment

Exclusion Criteria

  1. Receipt of effective antibacterial drug therapy for complicated urinary tract infection (cUTI) for a continuous duration of more than 24 hours during the previous 72 hours. Patients who have objective documentation of clinical progression of cUTI while on antibacterial drug therapy, or patients who received antibacterial drugs for surgical prophylaxis and then develop cUTI, may be appropriate for enrollment.
  2. Subjects with an organism isolated from the urine within the last year known to be resistant to ertapenem
  3. Severe structural or functional urinary tract abnormality responsible for an intractable infection which in the opinion of the investigator would require > 10 days of therapy or post-treatment prophylaxis (eg. patients with chronic vesiculo-ureteral reflux).
  4. Uncomplicated UTI
  5. Patients with paraplegia/quadriplegia
  6. Hypotension with systolic blood pressure < 90 mm Hg
  7. Complicated UTI associated with complete obstruction, emphysematous pyelonephritis, known or suspected renal or perinephric abscess or expected to require surgical intervention (not placement of catheters) to achieve cure
  8. Patients with a known history of myasthenia gravis
  9. Patients who require concomitant administration of tizanidine or valproic acid
  10. Patients with a history of allergy to carbapenems or quinolones or amoxicillin-clavulanate or other beta-lactams, or hypersensitivity to probenecid
  11. Renal transplantation
  12. Patients requiring dialysis
  13. Acute or chronic prostatitis
  14. High risk for cUTI caused by Pseudomonas sp. (eg,. history of prior UTI due to Pseudomonas species, recent steroid use, others)
  15. Chronic indwelling catheters or stents
  16. Ileal loops or vesico-urethral reflux
  17. Recent trauma to the pelvis or urinary tract within the prior 30 days
  18. History of seizures
  19. Patients with a history of blood dyscrasias
  20. Patients with a history of uric acid kidney stones
  21. Patients with acute gouty attack
  22. Patients on chronic methotrexate therapy
  23. Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy test result within 24 hours of study entry, are otherwise known to be pregnant, or are currently breastfeeding an infant.
  24. Male subjects must agree to use of an effective barrier method of contraception during the study and for 14 days post treatment
  25. Patients known to have a history of liver or kidney disease or neutropenia as defined by the following baseline laboratory criteria:

    • Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 3 X Upper Limit of Normal
    • Total bilirubin > 2 X Upper Limit of Normal
    • Neutropenia (<1000 cells/mm3)
  26. Patients participating in any other clinical study that involved the administration of an investigational medication
  27. Patient immunocompromised
  28. Patients unlikely to comply with the protocol
  29. Patients considered unlikely to survive the 4-week study period or has a rapidly progressive or terminal illness

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): NCT03357614

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United States, California
Medical Facility
Bellflower, California, United States, 90706
Medical Facility
Chula Vista, California, United States, 91911
Medical Facility
La Mesa, California, United States, 91942
Medical Facility
La Palma, California, United States, 90623
Medical Facility
Torrance, California, United States, 90502
United States, Florida
Medical Facility
Miami Lakes, Florida, United States, 33014
United States, Georgia
Medical Facility
Columbus, Georgia, United States, 31904
United States, Idaho
Medical Facility
Idaho Falls, Idaho, United States, 83404
United States, Massachusetts
Medical Facility
Boston, Massachusetts, United States, 02111
United States, Michigan
Medical Facility
Royal Oak, Michigan, United States, 48073
United States, Montana
Medical Facility
Butte, Montana, United States, 59701
United States, Ohio
Medical Facility
Columbus, Ohio, United States, 43214
Medical Facility
Columbus, Ohio, United States, 43215
United States, Texas
Medical Facility
Dallas, Texas, United States, 75246
Medical Facility
Houston, Texas, United States, 77057
Medical Facility
Kohtla-Järve, Estonia, 31025
Medical Facility
Tallinn, Estonia, 10617
Medical Facility
Võru, Estonia, 65526
Medical Facility
Tbilisi, Georgia, 00144
Medical Facility
Tbilisi, Georgia, 00159
Medical Facility
Tbilisi, Georgia, 00160
Medical Facility
Baja, Hungary, 6500
Medical Facility
Budapest, Hungary, 01204
Medical Facility
Nagykanizsa, Hungary, 8800
Medical Facility
Nyiregyhaza, Hungary, 4400
Medical Facility
Szentes, Hungary, 06600
Medical Facility
Tatabánya, Hungary, 2800
Medical Facility
Daugavpils, Latvia, LV5417
Medical Facility
Liepāja, Latvia, LV3414
Medical Facility
Riga, Latvia, LV1002
Medical Facility
Riga, Latvia, LV1038
Medical Facility
Valmiera, Latvia, LV4201
Sponsors and Collaborators
Iterum Therapeutics, International Limited
  Study Documents (Full-Text)

Documents provided by Iterum Therapeutics, International Limited:
Study Protocol  [PDF] June 4, 2018
Statistical Analysis Plan  [PDF] February 11, 2020

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Responsible Party: Iterum Therapeutics, International Limited Identifier: NCT03357614    
Other Study ID Numbers: IT001-302
First Posted: November 30, 2017    Key Record Dates
Results First Posted: December 29, 2020
Last Update Posted: December 29, 2020
Last Verified: November 2019
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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Urinary Tract Infections
Urologic Diseases
Clavulanic Acid
Clavulanic Acids
Amoxicillin-Potassium Clavulanate Combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
beta-Lactamase Inhibitors
Uricosuric Agents
Gout Suppressants
Antirheumatic Agents
Renal Agents