Complicated Urinary Tract InfectionsPhase 3NCT03357614
Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Complicated UTI in Adults
A Phase 3 study testing Sulopenem, Sulopenem-Etzadroxil/Probenecid and Ertapenem in people with Complicated Urinary Tract Infections, run by Iterum Therapeutics, International Limited at 32 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complicated Urinary Tract Infections
- What is being tested?
- Sulopenem, Sulopenem-Etzadroxil/Probenecid and Ertapenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,395 participants
- Where
- 32 sitesin 5 countries
- Study dates
- 18 Sep 2018to 14 Dec 2019
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 years of age with more than 24 hours of urinary symptoms attributable to a UTI
- Able to provide informed consent
- Clinically documented pyelonephritis or complicated urinary tract infection:
- Pyelonephritis with normal anatomy
- Complicated UTI as defined by one or more of the following factors:
- 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
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- At least two of the following signs or symptoms:
- Rigors, chills or fever/hypothermia
- Flank pain or pelvic pain
- Nausea or vomiting
- Dysuria, urinary frequency or urinary urgency
- Costovertebral angle tenderness on physical examination
- A mid-stream urine specimen with:
- a dipstick analysis positive for nitrite AND
- 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
Who cannot join
- 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.
- Subjects with an organism isolated from the urine within the last year known to be resistant to ertapenem
- 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).
- Uncomplicated UTI
- Patients with paraplegia/quadriplegia
- Hypotension with systolic blood pressure < 90 mm Hg
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- 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
- Patients with a known history of myasthenia gravis
- Patients who require concomitant administration of tizanidine or valproic acid
- Patients with a history of allergy to carbapenems or quinolones or amoxicillin-clavulanate or other beta-lactams, or hypersensitivity to probenecid
- Renal transplantation
- Patients requiring dialysis
- Acute or chronic prostatitis
- High risk for cUTI caused by Pseudomonas sp. (eg,. history of prior UTI due to Pseudomonas species, recent steroid use, others)
- Chronic indwelling catheters or stents
- Ileal loops or vesico-urethral reflux
- Recent trauma to the pelvis or urinary tract within the prior 30 days
- History of seizures
- Patients with a history of blood dyscrasias
- Patients with a history of uric acid kidney stones
- Patients with acute gouty attack
- Patients on chronic methotrexate therapy
- 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.
- Male subjects must agree to use of an effective barrier method of contraception during the study and for 14 days post treatment
- 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)
- Patients participating in any other clinical study that involved the administration of an investigational medication
- Patient immunocompromised
- Patients unlikely to comply with the protocol
- Patients considered unlikely to survive the 4-week study period or has a rapidly progressive or terminal illness
Trial locations and contacts
32 sites in 5 countries.
32 sites in 5 countries
United States15 sites
Medical Facility
Bellflower, California, 90706
Medical Facility
Boston, Massachusetts, 02111
Medical Facility
Butte, Montana, 59701
Medical Facility
Chula Vista, California, 91911
Medical Facility
Columbus, Georgia, 31904
Medical Facility
Columbus, Ohio, 43214
Medical Facility
Columbus, Ohio, 43215
Medical Facility
Dallas, Texas, 75246
Medical Facility
Houston, Texas, 77057
Medical Facility
Idaho Falls, Idaho, 83404
Medical Facility
La Mesa, California, 91942
Medical Facility
La Palma, California, 90623
Medical Facility
Miami Lakes, Florida, 33014
Medical Facility
Royal Oak, Michigan, 48073
Medical Facility
Torrance, California, 90502
Hungary6 sites
Medical Facility
Baja, 6500
Medical Facility
Budapest, 01204
Medical Facility
Nagykanizsa, 8800
Medical Facility
Nyíregyháza, 4400
Medical Facility
Szentes, 06600
Medical Facility
Tatabánya, 2800
Latvia5 sites
Medical Facility
Daugavpils, LV5417
Medical Facility
Liepāja, LV3414
Medical Facility
Riga, LV1002
Medical Facility
Riga, LV1038
Medical Facility
Valmiera, LV4201
Estonia3 sites
Medical Facility
Kohtla-Järve, 31025
Medical Facility
Tallinn, 10617
Medical Facility
Võru, 65526
Georgia3 sites
Medical Facility
Tbilisi, 00144
Medical Facility
Tbilisi, 00159
Medical Facility
Tbilisi, 00160
About this study
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
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.
- Conditions
- Complicated Urinary Tract Infections
- Being tested
- Sulopenem, Sulopenem-Etzadroxil/Probenecid, Ertapenem, Ciprofloxacin, Amoxicillin-clavulanate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SulopenemDrug
Antibiotic therapy for complicated UTI
Sulopenem-Etzadroxil/ProbenecidDrug
Antibiotic therapy for complicated UTI
ErtapenemDrug
Also called Invanz
Antibiotic therapy for complicated UTI
CiprofloxacinDrug
Also called Cipro
Antibiotic therapy for complicated UTI
Amoxicillin-clavulanateDrug
Also called Augmentin
Antibiotic therapy for complicated UTI
| Study group | Role | What they receive |
|---|---|---|
| Sulopenem | Experimental | 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 Receives: Drug: Sulopenem; Drug: Sulopenem-Etzadroxil/Probenecid |
| Ertapenem | Active comparator | 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 Receives: Drug: Ertapenem; Drug: Ciprofloxacin; Drug: Amoxicillin-clavulanate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Overall Success
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)
Measured: Day 21 +/- 1 day
Secondary outcomes (1)
Percentage of Participants With Microbiologic Success
Microbiologic success is defined as demonstrating <1000 CFU/mL of the baseline urpathogen by quantitative urine culture
Measured: Day 21 +/- 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2017
- Study start18 Sep 2018
- Primary completion14 Dec 2019
- Study completion14 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Complicated Urinary Tract InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,395 participants (actual)
Sponsor and investigators
- Lead sponsor
- Iterum Therapeutics, International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03357614
- Sponsor's protocol ID
- IT001-302
- Status last verified
- Nov 2019
- First submitted
- 20 Nov 2017
- Last updated
- 29 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dunne MW, Aronin SI, Das AF, Akinapelli K, Breen J, Zelasky MT, Puttagunta S. Sulopenem for the Treatment of Complicated Urinary Tract Infections Including Pyelonephritis: A Phase 3, Randomized Trial. Clin Infect Dis. 2023 Jan 6;76(1):78-88. doi: 10.1093/cid/ciac704.
PubMed 36068705