Complicated Urinary Tract InfectionsPhase 3IGNITE3NCT03032510
Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections
A Phase 3 study testing Eravacycline, Ertapenem and Levofloxacin in people with Complicated Urinary Tract Infections, run by Tetraphase Pharmaceuticals, Inc at 69 sites in 12 countries.
Trial summary
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI). 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?
- Eravacycline, Ertapenem and Levofloxacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,205 participants
- Where
- 69 sitesin 12 countries
- Study dates
- Jan 2017to Jan 2018
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participant with either:
- Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total population), or
- cUTI with at least one of the following conditions associated with a risk for developing cUTI:
- Indwelling urinary catheter
- Urinary retention (at least approximately 100 milliliters (mL) of residual urine after voiding)
- History of neurogenic bladder
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- Partial obstructive uropathy (for example, nephrolithiasis, bladder stones, and ureteral strictures)
- Azotemia of renal origin (not congestive heart failure [CHF] or volume related) such that the serum blood urea nitrogen [BUN] is elevated (>20 milligrams [mg]/deciliters [dL]) and the serum BUN:creatinine ratio is <15
- Surgically modified or abnormal urinary tract anatomy (for example, bladder diverticula, redundant urine collection system) except urinary tract surgery within the last 30 days (placing of stents or catheters is not considered to be surgical modification)
- At least 18 years of age at time of consent
- Able to provide informed consent
- At least two of the following signs or symptoms:
- Chills, rigors, or warmth associated with fever or hypothermia
- Flank pain (pyelonephritis) or pelvic pain (cUTI)
- Nausea or vomiting
- Dysuria, urinary frequency, or urinary urgency
- Costo-vertebral angle tenderness on physical examination
- Urine specimen with evidence of pyuria
- Dipstick analysis positive for leukocyte esterase (where positive result is at least "++" as indicated on the urine dipstick provided in the laboratory kit), or
- ≥10 white blood cells (WBCs) per cubic millimeter, or
- ≥10 WBCs per high power field
- If male: must agree to use an effective barrier method of contraception (for example, condom) during the study and for 14 days following the last dose if sexually active with a female of childbearing potential
- If female, not pregnant or nursing or, if of childbearing potential: must commit to either use at least two medically accepted, effective methods of birth control (for example, condom, spermicidal gel, oral contraceptive, indwelling intrauterine device, hormonal implant /patch, injections, approved cervical ring) during study drug dosing and for 14 days following last study drug dose or practicing sexual abstinence
Who cannot join
- Use of systemic antibiotics effective in cUTI within 72 hours prior to enrollment except under the following circumstances:
- Participants with suspected acute cUTI who have received a single dose of effective non-study antibiotics for the acute cUTI
- Signs and symptoms of cUTI developed while on the antibiotic for another indication
- History of an ertapenem-resistant urinary tract infection within 1 year of enrollment
- Likely to require >10 days of antibiotic treatment to cure the acute cUTI or likely to receive ongoing antibacterial drug prophylaxis prior to the Follow Up visit (21-28 days after randomization) [for example, participants with chronic vesiculo-ureteral reflux]
- Unlikely to survive at least through the duration of the study
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- Hypotension, systolic blood pressure ≤90 millimeters of mercury [mmHg]
- Complicated pyelonephritis with complete obstruction or known or suspected renal or perinephric abscess, emphysematous pyelonephritis, or Any condition likely to require surgery to achieve cure (this does not include procedure to place catheters or obtain diagnosis)
- Known or suspected urinary fungal infection
- Uncomplicated lower urinary tract infections
- Suspected or confirmed active prostatitis, or currently under treatment for prostatitis
- High risk for cUTI due to Pseudomonas (for example, history of prior cUTIs due to Pseudomonas, ≥20 mg once a day prednisone or equivalent steroid, and other risk factors as perceived by the Investigator)
- History of renal transplantation
- Presence of an ileal loop
- Any history of trauma to the pelvis or urinary tract occurring within 30 days of screening
- Indwelling urinary catheters present at screening which are not expected to be removed or replaced within 72 hours of enrollment (for example, nephrostomy tubes, stents, urethral and suprapubic catheters).
- Known concomitant human immunodeficiency virus (HIV) infection with CD4 counts below 200 within the last six months, or an acquired immune deficiency syndrome (AIDS) defining diagnosis within the last six months
- Neutropenia (Absolute neutrophil count <1,000 polymorphonuclear leukocytes [PMNs]/microliters [µL])
- Participation in a study with an experimental drug or device within 30 days prior to enrollment
- Known or suspected hypersensitivity to tetracyclines, carbapenems, or β-lactams
- History of seizures
- Any other unstable or clinically significant concurrent medical condition (for example, immunosuppressive therapy, chemotherapy, class IV heart or lung disease, end stage renal disease, or requiring hemodialysis) that would, in the opinion of the Investigator, jeopardize the safety of a participant and/or their compliance with the protocol
Trial locations and contacts
69 sites in 12 countries.
69 sites in 12 countries
Ukraine14 sites
Study site
Chernihiv
Study site
Chernivtsi
Study site
Dnipro
Study site
Ivano-Frankivsk
Study site
Kharkiv
Study site
Kyiv
Study site
Lviv
Study site
Mykolaiv
Study site
Odesa
Study site
Poltava
Study site
Uzhhorod
Study site
Vinnytsia
Study site
Zaporizhia
Study site
Zhytomyr
United States10 sites
Study site
Baytown, Texas
Study site
Columbus, Georgia, 31820
Study site
Coral Gables, Florida
Study site
Doral, Florida
Study site
Fullerton, California
Study site
Las Vegas, Nevada
Study site
Los Angeles, California
Study site
Miami, Florida
Study site
St Louis, Missouri
Study site
Torrance, California
Bulgaria8 sites
Study site
Pleven
Study site
Plovdiv
Study site
Razgrad
Study site
Rousse
Study site
Smyadovo
Study site
Sofia
Study site
Varna
Study site
Veliko Tarnovo
Hungary8 sites
Study site
Baja
Study site
Budapest
Study site
Miskolc
Study site
Nagykanizsa
Study site
Nyíregyháza
Study site
Sopron
Study site
Szentes
Study site
Tatabánya
Russia8 sites
Study site
Arkhangelsk
Study site
Moscow
Study site
Pyatigorsk
Study site
Rostov-on-the-Don
Study site
Saint Petersburg
Study site
Smolensk
Study site
Vsevolozhsk
Study site
Yaroslavl
Slovakia5 sites
Study site
Nitra
Study site
Poprad
Study site
Prešov
Study site
Svidník
Study site
Žilina
Romania4 sites
Study site
Brasov
Study site
Bucharest
Study site
Craiova
Study site
Oradea
About this study
Official title: A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of IV Eravacycline Compared With Ertapenem in Complicated Urinary Tract Infections
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI).
Read the detailed description
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI).
This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy, safety and pharmacokinetics of eravacycline compared with ertapenem in the treatment of cUTI.
Randomization will be stratified based on two criteria: (1) by primary site of infection (pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the receipt of a single dose of effective non-study antibiotics for the acute cUTI within 72 hours prior to randomization. An enrollment cap of approximately 50% is planned for subjects with pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of approximately 20% is planned for subjects who have received a single dose of non-study antibiotics for the acute cUTI within 72 hours prior to randomization.
In this study subjects will be enrolled and randomized to one of two treatment arms in a 1:1 ratio: (i) eravacycline intravenously (IV) / levofloxacin (PO), or (ii) ertapenem (IV) / levofloxacin (PO).
- Conditions
- Complicated Urinary Tract Infections
- Being tested
- Eravacycline, Ertapenem, Placebo, Levofloxacin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EravacyclineDrug
Also called TP-434
ErtapenemDrug
Also called Invanz
PlaceboDrug
LevofloxacinDrug
Also called Levaquin
| Study group | Role | What they receive |
|---|---|---|
| Eravacycline (Intravenous)/Levofloxacin (Oral) | Experimental | Not described Receives: Drug: Eravacycline; Drug: Placebo; Drug: Levofloxacin |
| Ertapenem (Intravenous)/Levofloxacin (Oral) | Active comparator | Not described Receives: Drug: Ertapenem; Drug: Placebo; Drug: Levofloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit
This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Measured: End of Infusion
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit
This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Measured: TOC visit (14-17 days after randomization)
Secondary outcomes (1)
Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit
Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry.
Clinical failure: Subjects were classified as clinical failure in the event of
- Death related to cUTI at any timepoint
- Persistence of clinical symptoms of cUTI or new symptoms developed
- Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.
Measured: TOC visit (14-17 days after randomization)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionDec 2017
- Study completionJan 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.
- 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
- 1,205 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tetraphase Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Tetraphase Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03032510
- Sponsor's protocol ID
- TP-434-021
- Acronym
- IGNITE3
- Status last verified
- Dec 2021
- First submitted
- 17 Jan 2017
- Last updated
- 6 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of IV Eravacycline Compared With Ertapenem in Complicated Urinary Tract Infections
- ClinicalTrials.gov ID
- NCT03032510
- Acronym / sponsor ID
- IGNITE3 / TP-434-021
- Conditions
- Complicated Urinary Tract Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,205 participants (actual)
- Lead sponsor
- Tetraphase Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- Jan 2017 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 26 Jan 2017 (estimated)
- Results
- Posted 2 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI).
Detailed description
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI).
This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy, safety and pharmacokinetics of eravacycline compared with ertapenem in the treatment of cUTI.
Randomization will be stratified based on two criteria: (1) by primary site of infection (pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the receipt of a single dose of effective non-study antibiotics for the acute cUTI within 72 hours prior to randomization. An enrollment cap of approximately 50% is planned for subjects with pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of approximately 20% is planned for subjects who have received a single dose of non-study antibiotics for the acute cUTI within 72 hours prior to randomization.
In this study subjects will be enrolled and randomized to one of two treatment arms in a 1:1 ratio: (i) eravacycline intravenously (IV) / levofloxacin (PO), or (ii) ertapenem (IV) / levofloxacin (PO).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eravacycline (Intravenous)/Levofloxacin (Oral) | Experimental | Drug: Eravacycline, Drug: Placebo, Drug: Levofloxacin |
| Ertapenem (Intravenous)/Levofloxacin (Oral) | Active comparator | Drug: Ertapenem, Drug: Placebo, Drug: Levofloxacin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Male or female participant with either:
- At least 18 years of age at time of consent
- Able to provide informed consent
- At least two of the following signs or symptoms:
- Urine specimen with evidence of pyuria
Key exclusion criteria (22 listed)
- Use of systemic antibiotics effective in cUTI within 72 hours prior to enrollment except under the following circumstances:
- History of an ertapenem-resistant urinary tract infection within 1 year of enrollment
- Likely to require >10 days of antibiotic treatment to cure the acute cUTI or likely to receive ongoing antibacterial drug prophylaxis prior to the Follow Up visit (21-28 days after randomization) [for example, participants with chronic vesiculo-ureteral reflux]
- Unlikely to survive at least through the duration of the study
- Hypotension, systolic blood pressure ≤90 millimeters of mercury [mmHg]
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 |
|---|---|---|
| EravacyclineAlso: TP-434 | Drug | Eravacycline (Intravenous)/Levofloxacin (Oral) |
| ErtapenemAlso: Invanz | Drug | Ertapenem (Intravenous)/Levofloxacin (Oral) |
| Placebo | Drug | Eravacycline (Intravenous)/Levofloxacin (Oral), Ertapenem (Intravenous)/Levofloxacin (Oral) |
| LevofloxacinAlso: Levaquin | Drug | Eravacycline (Intravenous)/Levofloxacin (Oral), Ertapenem (Intravenous)/Levofloxacin (Oral) |
Primary outcome
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit
Time frame: End of Infusion
This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit
Time frame: TOC visit (14-17 days after randomization)
This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
1 secondary outcome
Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit
Time frame: TOC visit (14-17 days after randomization)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Chief Medical Officer study director
Tetraphase Pharmaceuticals
69 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eravacycline, Ertapenem and Levofloxacin in people with Complicated Urinary Tract Infections, run by Tetraphase Pharmaceuticals, Inc at 69 sites in 12 countries.
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 23 inclusion and 22 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 6 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 69 sites in Ukraine, United States, Bulgaria, Hungary, Russia and 7 more countries. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 2 Oct 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?
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit (time frame: End of Infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jan 2022.