Efficacy and Safety Study of Eravacycline Compared With Levofloxacin in Complicated Urinary Tract Infections
- Registration Number
- NCT01978938
- Lead Sponsor
- Tetraphase Pharmaceuticals, Inc.
- Brief Summary
This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy and safety of eravacycline compared with levofloxacin in participants with complicated urinary tract infections (cUTI).
- Detailed Description
This study began with a 3-arm Lead-in portion to determine the oral (PO) dosing (200 or 250 milligrams \[mg\]) of eravacycline to be used with intravenously (IV) administered eravacycline for the Pivotal portion (2 arms). A PO dose of 200 mg was selected based on the unblinded Lead-in analysis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 908
- Male and female participants with either:
a. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total population), OR b. cUTI with at least 1 of the following conditions associated with a risk for developing cUTI: i. Indwelling urinary catheter ii. Urinary retention (approximately 100 milliliters of residual urine after voiding) iii. Neurogenic bladder iv. Partial obstructive uropathy (such as, nephrolithiasis, bladder stones, and ureteral strictures) v. Azotemia of renal origin (not congestive heart failure or volume related) such that the serum blood urea nitrogen (BUN) is elevated (>20 mg/deciliters) AND the serum BUN: creatinine ratio is <15 vi. Surgically modified or abnormal urinary tract anatomy (such as, bladder diverticula, redundant urine collection system) EXCEPT surgery within the last month
-
Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in participants with cUTI, including:
-
Participants with a history of a levofloxacin-resistant urinary tract infection
-
Likely to receive ongoing antibacterial drug prophylaxis prior to the late Post-Treatment visit (such as, participants with vesiculo-ureteral reflux)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Eravacycline Eravacycline Eravacycline was administered IV at a dose of 1.5 mg per kilogram (kg) of body weight every 24 hours (q24h). At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO twice a day for a total therapy of 7 dosing cycles. Levofloxacin Levofloxacin Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO once a day for a total therapy of 7 dosing cycles.
- Primary Outcome Measures
Name Time Method Participants In The Microbiological Intent-To-Treat (Micro-ITT) Population With A Responder Outcome At The Post-Treatment (PT) Visit PT Visit This was the primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to levofloxacin 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.
- Secondary Outcome Measures
Name Time Method Participants In The Microbiological Modified ITT (Micro-MITT) Population With A Microbiological Response PT Visit This outcome measure (FDA and the European Medicines Agency \[EMA\]) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the micro-MITT population. Responses were success, failure, or indeterminate/missing. Success was considered a reduction of the baseline pathogen(s) to \<10\^4 CFU/mL. Failure required blood cultures at or beyond end of therapy (EOT) to be positive for baseline pathogen(s), or urine culture to grow ≥10\^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available.
Participants In The Microbiologically Evaluable (ME) Population With A Microbiological Response PT Visit This outcome measure (FDA and EMA) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the ME population. Responses were either success or failure. Indeterminate/missing responses were not included. Success was considered a reduction of the baseline pathogen(s) to \<10\^4 CFU/mL. Failure required blood cultures at or beyond EOT to be positive for baseline pathogen(s), or urine culture to grow ≥10\^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available. Populations: ME, all micro-ITT and clinically-evaluable (CE) participants with a suitable urine specimen and an interpretable urine culture; micro-ITT, all participants with ≥1 baseline bacterial pathogen from a urine or blood culture that caused a UTI against which eravacycline had expected antibacterial activity; ITT, all randomized participants, regardless of receiving study drug or not.
Trial Locations
- Locations (99)
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Columbus Regional Research Institute
🇺🇸Columbus, Ohio, United States
Thomayer Hospital, Department of Urology
🇨🇿Prague, Czechia
Sunrise Hospital and Medical Centre
🇺🇸Las Vegas, Nevada, United States
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic
🇧🇬Pleven, Bulgaria
University Multiprofile Hospital for Active Treatment "Aleksandrovska", Sofia, Department of Laparoscopic Urology
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic
🇧🇬Sofia, Bulgaria
Multiprofile Regional Hospital for Active Treatment "Dr. Stefan Cherkezov", Veliko Tarnovo, Department of Urology
🇧🇬Veliko Tarnovo, Bulgaria
Fundacion Cardiomet
🇨🇴Armenia, Colombia
De la Costa Clinic. Ltd. Research Centre
🇨🇴Barranquilla, Colombia
University Hospital Brno, Clinic of Urology
🇨🇿Brno, Czechia
Hospital Novy Jicin, Department of Urology
🇨🇿Novy Jicin, Czechia
University Hospital Olomouc
🇨🇿Olomouc, Czechia
East Viru Central Hospital, Surgery Clinic
🇪🇪Kohtla-Jarve, Estonia
University Hospital Hradec Kralove, Clinic of Urology
🇨🇿Hradec Kralove, Czechia
West Tallinn Central Hospital, Department of Urology
🇪🇪Tallinn, Estonia
East Tallinn Central Hospital, Department of Internal Medicine
🇪🇪Tallinn, Estonia
Tartu University Hospital, Surgery Clinic, Department of Urology and Renal Transplantation
🇪🇪Tartu, Estonia
Western Georgia National Medical Center
🇬🇪Kutaisi, Georgia
Research Institute of Clinical Medicine
🇬🇪Tbilisi, Georgia
Aversi Clinic
🇬🇪Tbilisi, Georgia
Modern Medical Technologies - Guram Karazanashvili's clinic
🇬🇪Tbilisi, Georgia
Evaggelismos Hospital
🇬🇷Kolonaki, Greece
Petz Aladar County Teaching Hospital, Department of Urology
🇭🇺Gyor, Hungary
Papageorgiou General Hospital
🇬🇷Thessaloníki, Greece
Principal SMO Kft.
🇭🇺Baja, Hungary
St. Borbala Hospital, Department of Urology
🇭🇺Tatabanya, Hungary
Jahn Ferenc South Pest Hospital, Department of Urology
🇭🇺Budapest, Hungary
Elisabeth Teaching Hospital and Rehabilitation Institute of Sopron, Department of Urology
🇭🇺Sopron, Hungary
Csongrad County Dr. Bugyi Istvan Hospital, Department of Urology
🇭🇺Szentes, Hungary
Zion Medical Center
🇮🇱Haifa, Israel
Hospital Mater Domini
🇮🇹Castellanza, Italy
Liepajas Regional Hospital
🇱🇻Liepaja, Latvia
P. Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Riga East University Hospital, LLC
🇱🇻Riga, Latvia
SIA 'URO' Clinic
🇱🇻Riga, Latvia
Vidzemes Hospital
🇱🇻Valmiera, Latvia
National Scientific Practical Center for Emergency Medicine, Department of Urology
🇲🇩Chisinau, Moldova, Republic of
Hospital Civil Fray Antonio Alcalde
🇲🇽Guadalajara, Mexico
Hospital Civil Guadalajara Dr. Juan I. Mendoza
🇲🇽Guadalajara, Mexico
Republican Clinical Hospital, Department of Urology
🇲🇩Chisinau, Moldova, Republic of
Boni Fratres Catoviensis Sp. z o.o., Department of Internal Diseases with Cardiologic Diagnostics Unit
🇵🇱Katowice, Poland
Military Medical Academy University Teaching Hospital - Central Veterans' Hospital, Clinical and Didactic Center of the Medical University of Lodz, Teaching Department of Nephrology, Hypertension and Renal Transplantation
🇵🇱Lodz, Poland
Medicome Sp. z o.o.
🇵🇱Oswiecim, Poland
HEUREKA Hanna Szalecka
🇵🇱Piaseczno, Poland
Emergency Clinical County Hospital Brasov
🇷🇴Brasov, Romania
Pope John Paul 2nd Independent Public Provincial Hospital
🇵🇱Zamość, Poland
"Prof. Dr. Th. Burghele" Clinical Hospital
🇷🇴Bucharest, Romania
Delta Hospital
🇷🇴Bucharest, Romania
Craiova Emergency Clinical County Hospital
🇷🇴Craiova, Romania
Clinical Hospital "Dr. C. I. Parhon"
🇷🇴Iași, Romania
Sibiu County Emergency Clinical Hospital
🇷🇴Sibiu, Romania
Oradea Clinical Municipal Hospital "Dr. Gavril Curteanu"
🇷🇴Oradea, Romania
Federal Clinical Center for High Medical Technologies
🇷🇺Moscow, Russian Federation
Central Clinical Hospital of Civil Aviation
🇷🇺Moscow, Russian Federation
Penza Regional Clinical Hospital n.a. N.N. Burdenko
🇷🇺Penza, Russian Federation
City Clinical Hospital of Emergency Care #2
🇷🇺Novosibirsk, Russian Federation
Saint-Petersburg Scientific Research Institute for Phthisiopulmonology
🇷🇺Saint Petersburg, Russian Federation
St. Petersburg Clinical Hospital under the Russian Academy of Sciences
🇷🇺Saint Petersburg, Russian Federation
St. Petersburg State Healthcare Institution: City Hospital #15
🇷🇺Saint Petersburg, Russian Federation
St. Petersburg State Healthcare Institution: St. George the Martyr City Hospital
🇷🇺Saint Petersburg, Russian Federation
St. Petersburg State-Funded Healthcare Institution: City Hospital #26
🇷🇺Saint Petersburg, Russian Federation
Saratov State Medical University n.a. V.I. Razumovsky
🇷🇺Saratov, Russian Federation
Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
Vsevolozhsk Clinical Central District Hospital
🇷🇺Vsevolozhsk, Russian Federation
Clinresco Centres
🇿🇦Kempton Park, South Africa
Lakeview Hospital
🇿🇦Benoni, South Africa
Mzansi Ethical Research Centre
🇿🇦Middleburg, South Africa
St. Georges Hospital
🇿🇦Port Elizabeth, South Africa
Regional Municipal Institution "Chernivtsi Regional Hospital"
🇺🇦Chernivtsi, Ukraine
Dnipropetrovsk City Multispecialty Clinical Hospital #4
🇺🇦Dnipropetrovsk, Ukraine
Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital
🇺🇦Dnipropetrovsk, Ukraine
O.I. Meschaninov Clinical Hospital of Emergency and Urgent Medical Care
🇺🇦Kharkiv, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦Ivano-Frankivs'k, Ukraine
Ivano-Frankivsk City Clinical Hospital #1
🇺🇦Ivano-Frankivs'k, Ukraine
Shapoval Regional Clinical Center of Urology and Nephrology
🇺🇦Kharkiv, Ukraine
Institute of Urology
🇺🇦Kyiv, Ukraine
Khmelnytskyi Regional Hospital
🇺🇦Khmel'nyts'kyy, Ukraine
Lviv Regional Clinical Hospital
🇺🇦L'viv, Ukraine
Volyn Regional Clinical Hospital
🇺🇦Luts'k, Ukraine
Mykolaiv Regional Hospital, Center for Nephrology and Dialysis
🇺🇦Mykolaiv, Ukraine
City Clinical Hospital #10, Urology Department #1
🇺🇦Odesa, Ukraine
Odesa Regional Clinical Hospital
🇺🇦Odessa, Ukraine
Poltava M.V. Sklifosovskyi Regional Clinical Hospital
🇺🇦Poltava, Ukraine
Vinnytsia M.I. Pyrohov Regional Clinical Hospital
🇺🇦Vinnytsya, Ukraine
Municipal Institution "Zaporizhzhia Reqional Clinical Hospital" of Zaporizhzhia Regional Councill
🇺🇦Zaporizhzhya, Ukraine
San Diego Clinical Trials
🇺🇸San Diego, California, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Nephrology
🇧🇬Gabrovo, Bulgaria
Multiprofile Hospital for Active Treatment "Dr. Stamen Iliev", Montana, Department of Nephrology and Dialysis
🇧🇬Montana, Bulgaria
Multiprofile Hospital for Active Treatment, Ruse, Department of Urology
🇧🇬Rousse, Bulgaria
Tsulukidze National Center of Urology
🇬🇪Tbilisi, Georgia
City Clinical Hospital #57 under Moscow Healthcare Department
🇷🇺Moscow, Russian Federation
Novgorod Regional Clinical Hospital
🇷🇺Veliky Novgorod, Russian Federation
State Institution: Uzhhorod Railway Station Clinical Hospital under State Territorial Industry-Specific Association:Lviv Railway
🇺🇦Uzhhorod, Ukraine
Rostov State Medical University
🇷🇺Rostov-on-Don, Russian Federation
North-Western State Medical University n.a. I.I. Mechnikov
🇷🇺Saint Petersburg, Russian Federation
Multiprofile Hospital for Active Treatment, Sofia at Military Medical Academy, General Urology Clinic
🇧🇬Sofia, Bulgaria