Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03032510
• Date of registration: 17/01/2017
• Prospective Registration: No
• Primary sponsor: Tetraphase Pharmaceuticals, Inc.
• Public title: Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections IGNITE3
• Scientific 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
• Date of first enrolment: January 2017
• Target sample size: 1205
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03032510
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Austria, Bulgaria, Estonia, Georgia, Hungary, Latvia, Moldova, Republic of, Romania, Russian Federation, Slovakia, Ukraine, United States

Contacts

• Name: Chief Medical Officer
• Affiliation: Tetraphase Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female participant with either:

1. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total
population), or

2. 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

- 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)

2. At least 18 years of age at time of consent

3. Able to provide informed consent

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

1. Chills, rigors, or warmth associated with fever or hypothermia

2. Flank pain (pyelonephritis) or pelvic pain (cUTI)

3. Nausea or vomiting

4. Dysuria, urinary frequency, or urinary urgency

5. Costo-vertebral angle tenderness on physical examination

5. Urine specimen with evidence of pyuria

1. Dipstick analysis positive for leukocyte esterase (where positive result is at
least "++" as indicated on the urine dipstick provided in the laboratory kit), or

2. =10 white blood cells (WBCs) per cubic millimeter, or

3. =10 WBCs per high power field

6. 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

7. 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

Exclusion Criteria:

1. Use of systemic antibiotics effective in cUTI within 72 hours prior to enrollment
except under the following circumstances:

1. Participants with suspected acute cUTI who have received a single dose of
effective non-study antibiotics for the acute cUTI

2. Signs and symptoms of cUTI developed while on the antibiotic for another
indication

2. History of an ertapenem-resistant urinary tract infection within 1 year of enrollment

3. 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]

4. Unlikely to survive at least through the duration of the study

5. Hypotension, systolic blood pressure =90 millimeters of mercury [mmHg]

6. 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)

7. Known or suspected urinary fungal infection

8. Uncomplicated lower urinary tract infections

9. Suspected or confirmed active prostatitis, or currently under treatment for
prostatitis

10. 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)

11. History of renal transplantation

12. Presence of an ileal loop

13. Any history of trauma to the pelvis or urinary tract occurring within 30 days of
screening

14. 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).

15. 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

16. Neutropenia (Absolute neutrophil count <1,000 polymorphonuclear leukocytes
[PMNs]/microliters [µL])

17. Participation in a study with an experimental drug or device within 30 days prior to
enrollment

18. Known or suspected hypersensitivity to tetracyclines, carbapenems, or ß-lactams

19. History of seizures

20. 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Complicated Urinary Tract Infections

Intervention(s)

Drug: Levofloxacin

Drug: Eravacycline

Drug: Placebo

Drug: Ertapenem

Primary Outcome(s)

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)]

Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit [Time Frame: End of Infusion]

Secondary Outcome(s)

Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit [Time Frame: TOC visit (14-17 days after randomization)]

Secondary ID(s)

TP-434-021

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 02/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03032510