Complicated Urinary Tract InfectionPhase 2NCT03445195
Evaluation of Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections
A Phase 2 study testing Sulbactam-ETX2514 and Imipenem-cilastatin in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Entasis Therapeutics at 4 sites in Bulgaria.
Trial summary
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with complicated urinary tract infections (cUTIs) who are otherwise relatively healthy. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Complicated Urinary Tract Infection, Acute Pyelonephritis
- What is being tested?
- Sulbactam-ETX2514 and Imipenem-cilastatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 4 sitesBulgaria
- Study dates
- 17 Jan 2018to 17 May 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A signed informed consent form (ICF). If a study patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient as permitted by local law and institutional Standard Operating Procedures.
- Male or female, 18 to 90 years of age, inclusive.
- Expectation, in the judgment of the Investigator, that the patient's cUTI would require initial hospitalization and treatment with IV antibiotics.
- Documented or suspected cUTI or Acute pyelonephritis (AP).
Who cannot join
- Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter.
- Known non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization that would interfere with evaluation of response to the study antibiotics.
- Patient requires continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study.
- Receipt of a single dose of a long-acting, potentially-effective systemic antibiotic with activity against Gram-negative uropathogens for more than 24 hours within the 72-hour window prior to randomization.
- Requirement at time of randomization for any reason for additional systemic antimicrobial therapy (including antibacterial, antimycobacterial, or antifungal therapy) other than study drug, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis.
- Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study [from randomization through the Late Follow-up (LFU) Visit].
- Any patients previously randomized in this study.
Trial locations and contacts
4 sites in 1 country.
Bulgaria4 sites
Universeity Multiprofile Hospital for Active Teatment
Sofia, 1431
University Multiprofile Hospital for Active Teatment-Clinic of Nephrology
Sofia, 1431
Multiprofile Hospital for Active Teatment (MHAT) and Emergency Medicine - Pirogov
Sofia, 1606
Multiprofile Hospital for Active Teatment (MHAT) and Emergency Medicine - Doverie
Sofia, 1632
About this study
Official title: A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections, Including Acute Pyelonephritis
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with complicated urinary tract infections (cUTIs) who are otherwise relatively healthy.
Read the detailed description
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs who are otherwise relatively healthy. Patients with Acute Pyelonephritis may also be enrolled. Approximately 80 patients will be randomized to receive either 1 g ETX2514/1 g sulbactam IV or matching placebo every 6 hours (q6h). All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.
- Being tested
- Sulbactam-ETX2514, Placebo, Imipenem-cilastatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sulbactam-ETX2514Drug
Also called ETX2514SUL
The ETX2514SUL regimen of 1 g ETX2514/1 g sulbactam infused over 3 hours q6h.
PlaceboDrug
Matching 1g IV solution.
Imipenem-cilastatinDrug
All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.
| Study group | Role | What they receive |
|---|---|---|
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Experimental | Not described Receives: Drug: Sulbactam-ETX2514; Drug: Imipenem-cilastatin |
| Placebo + Imipenem/Cilastatin | Placebo comparator | Not described Receives: Drug: Placebo; Drug: Imipenem-cilastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Overall Success
The primary efficacy endpoint for this study was the proportion of patients with an overall success (clinical cure and micro-biologic eradication) for the m-MITT (Micro-biologically Modified Intent-to-Treat) Population at the TOC Visit.
Measured: From baseline through day 21
Secondary outcomes (2)
Clinical Cure
Proportion of patients with a response of clinical cure for the MITT(modified intent to treat), m-MITT (microbiologically modified intent to treat), CE(clinically evaluable), and ME(microbiologically evaluable) populations at the TOC(test of cure) visit.
Measured: Baseline to day 21
Microbiologic Eradication
Proportion of patients with a response of microbiologic eradication for the m-MITT(microbiologically modified intent to treat) and ME(microbiologically evaluable) populations at the TOC visit
Measured: Baseline to day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2018
- Study start17 Jan 2018
- Primary completion17 May 2018
- Study completion17 May 2018
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 InfectionStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Entasis Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anibal Calmaggi, MD, Study chair, Medpace, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03445195
- Sponsor's protocol ID
- CS2514-2017-0003
- Status last verified
- Jun 2019
- First submitted
- 20 Feb 2018
- Last updated
- 22 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sagan O, Yakubsevitch R, Yanev K, Fomkin R, Stone E, Hines D, O'Donnell J, Miller A, Isaacs R, Srinivasan S. Pharmacokinetics and Tolerability of Intravenous Sulbactam-Durlobactam with Imipenem-Cilastatin in Hospitalized Adults with Complicated Urinary Tract Infections, Including Acute Pyelonephritis. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01506-19. doi: 10.1128/AAC.01506-19. Print 2020 Feb 21.
PubMed 31843995
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections, Including Acute Pyelonephritis
- ClinicalTrials.gov ID
- NCT03445195
- Acronym / sponsor ID
- CS2514-2017-0003
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Entasis TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 17 Jan 2018 (actual)
- Primary completion
- 17 May 2018 (actual)
- Study completion
- 17 May 2018 (actual)
- First posted
- 26 Feb 2018 (actual)
- Results
- Posted 5 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with complicated urinary tract infections (cUTIs) who are otherwise relatively healthy.
Detailed description
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs who are otherwise relatively healthy. Patients with Acute Pyelonephritis may also be enrolled. Approximately 80 patients will be randomized to receive either 1 g ETX2514/1 g sulbactam IV or matching placebo every 6 hours (q6h). All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs.
| Arm | Type | Receives |
|---|---|---|
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Experimental | Drug: Sulbactam-ETX2514, Drug: Imipenem-cilastatin |
| Placebo + Imipenem/Cilastatin | Placebo comparator | Drug: Placebo, Drug: Imipenem-cilastatin |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- A signed informed consent form (ICF). If a study patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient as permitted by local law and institutional Standard Operating Procedures.
- Male or female, 18 to 90 years of age, inclusive.
- Expectation, in the judgment of the Investigator, that the patient's cUTI would require initial hospitalization and treatment with IV antibiotics.
- Documented or suspected cUTI or Acute pyelonephritis (AP).
Key exclusion criteria (7 listed)
- Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter.
- Known non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization that would interfere with evaluation of response to the study antibiotics.
- Patient requires continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study.
- Receipt of a single dose of a long-acting, potentially-effective systemic antibiotic with activity against Gram-negative uropathogens for more than 24 hours within the 72-hour window prior to randomization.
- Requirement at time of randomization for any reason for additional systemic antimicrobial therapy (including antibacterial, antimycobacterial, or antifungal therapy) other than study drug, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sulbactam-ETX2514Also: ETX2514SULThe ETX2514SUL regimen of 1 g ETX2514/1 g sulbactam infused over 3 hours q6h. | Drug | Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin |
| PlaceboMatching 1g IV solution. | Drug | Placebo + Imipenem/Cilastatin |
| Imipenem-cilastatinAll patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h. | Drug | Placebo + Imipenem/Cilastatin, Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin |
Primary outcome
Number of Participants With Overall Success
Time frame: From baseline through day 21
The primary efficacy endpoint for this study was the proportion of patients with an overall success (clinical cure and micro-biologic eradication) for the m-MITT (Micro-biologically Modified Intent-to-Treat) Population at the TOC Visit.
2 secondary outcomes
Clinical Cure
Time frame: Baseline to day 21
Microbiologic Eradication
Time frame: Baseline to day 21
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31843995Sagan O, Yakubsevitch R, Yanev K, Fomkin R, Stone E, Hines D, O'Donnell J, Miller A, Isaacs R, Srinivasan S. Pharmacokinetics and Tolerability of Intravenous Sulbactam-Durlobactam with Imipenem-Cilastatin in Hospitalized Adults with Complicated Urinary Tract Infections, Including Acute Pyelonephritis. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01506-19. doi: 10.1128/AAC.01506-19. Print 2020 Feb 21.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anibal Calmaggi, MD study chair
Medpace, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sulbactam-ETX2514 and Imipenem-cilastatin in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Entasis Therapeutics at 4 sites in Bulgaria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Overall Success (time frame: From baseline through day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03445195, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.