Clinical trial NCT03138733: Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia
Official title: A Randomized, Double-blind, Multi-center Study to Establish the Efficacy and Safety of Ceftobiprole Medocaril Compared to Daptomycin in the Treatment of Staphylococcus Aureus Bacteremia, Including Infective Endocarditis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Staphylococcus Aureus Bacteremia
Keywords: Ceftobiprole, daptomycin, Staphylococcus aureus
Bacteremia, bloodstream infection
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
First posted: 2017-05-03
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to compare the efficacy and safety of ceftobiprole medocaril versus a comparator in the treatment of patients with complicated Staphylococcus aureus bacteremia (SAB).

Detailed description: Patients were randomized 1:1 to ceftobiprole or the comparator regimen. Randomization was stratified by study site, dialysis status, and prior antibacterial treatment use within 7 days before randomization.

The three phases of the study were:

1. Screening assessments of up to 72 hours prior to randomization
2. Randomization and subsequent active treatment with intravenous (i.v.) study drug (ceftobiprole or daptomycin ± aztreonam).
3. Post-treatment, comprising an end of trial (EOT) visit (within 72 hours of last study-drug administration), Day 35 (± 3 days), Day 42 (± 3 days), and a post-treatment evaluation (PTE) visit on Day 70 (± 5 days) post-randomization.

Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 18 years of age
* Staphylococcus aureus bacteremia (SAB), based on at least one positive blood culture obtained within the 72 h prior to randomization
* At least one of the following signs or symptoms of bacteremia:

  1. fever (e.g.≥ 38 °C/100.4 °F measured orally)
  2. white blood cell count \> 10,000 or \< 4,000 cells/µL, or \> 10% immature neutrophils (bands)
  3. tachycardia (heart rate \> 90 bpm)
  4. hypotension (systolic blood pressure \< 90 mmHg)
* At least one of the following:

  1. SAB in patients undergoing chronic intermittent hemodialysis or peritoneal dialysis
  2. Persistent SAB
  3. Definite native-valve right-sided infective endocarditis by Modified Duke's Criteria
  4. Other forms of complicated SAB
  5. Osteomyelitis (including vertebral, sternal, or long-bone osteomyelitis)
  6. Epidural or cerebral abscess
* Other inclusion criteria have been applied

Exclusion Criteria:

* Treatment with potentially effective (anti-staphylococcal) systemic antibacterial treatment for more than 48 h within the 7 days prior to randomization; Exception: Documented failure of bloodstream clearance
* Bloodstream or non-bloodstream concomitant infections with Gram-negative bacteria that are known to be non-susceptible to either ceftobiprole or aztreonam
* Left-sided infective endocarditis
* Prosthetic cardiac valves or valve support rings, cardiac pacemakers, automatic implantable cardioverter-defibrillator, or left-ventricular assist devices
* Community- or hospital-acquired pneumonia
* Opportunistic infections within 30 days prior to randomization, where the underlying cause of these infections is still active
* Requirement for continuous renal-replacement therapy
* Women who are pregnant or nursing
* Other exclusion criteria have been applied

Primary outcomes:
measure: Number of Patients With or Without Overall Success at the Post-treatment Evaluation (PTE) Visit
timeFrame: PTE visit on Day 70 (± 5 days) post-randomization
Secondary outcomes:
measure: Number of Patients With or Without Overall Success at the PTE Visit in the CE Population
timeFrame: At PTE visit on Day 70 (± 5 days) post-randomization
measure: Number of Patients With Microbiological Eradication at the PTE Visit
timeFrame: At PTE visit on Day 70 (± 5 days) post-randomization
measure: All-cause Mortality at the PTE Visit
timeFrame: At PTE visit on Day 70 (± 5 days) post-randomization
measure: Number of Patients With or Without New Metastatic Foci or Other Complications of SAB Developed After Day 7
timeFrame: Assessment after Day 7 post-randomization through to post-treatment evaluation (PTE) visit on Day 70 (± 5 days)
measure: Time to Staphylococcus Aureus Bloodstream Clearance
timeFrame: Up to 6 weeks post-randomization
measure: Number of Patients With or Without Adverse Events (AEs)
timeFrame: AEs were assessed from the first dose of study drug through the post-treatment evaluation (PTE) visit on Day 70 (± 5 days)
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: eStudy Site - Chula Vista - PPDS
state: California
city: West Palm Beach
country: United States
facility: Triple O Medical Services Inc
state: Florida
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Las Vegas
country: United States
facility: eStudy Site - Las Vegas - PPDS
state: Nevada
city: Columbus
country: United States
facility: Remington Davis Inc.
state: Ohio
city: Buenos Aires
country: Argentina
facility: Central Hospital de San Isidro Melchor Posse
city: La Plata
country: Argentina
facility: Medical Institute Platense SA
city: Rosario
country: Argentina
facility: British Sanatorium SA
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Eurohospital Plovdiv", Plovdiv, Intensive Care Clinic
city: Ruse
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of General, Purulent-Septic, Pediatric and One Day Surgery
city: Sliven
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Dr. Ivan Seliminski", Sliven, Anesthesiology and Intensive Care Department
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Clinic of Purulent-Septic Surgery
city: Barranquilla
country: Colombia
facility: De La Costa Clinic Ltd.
city: Rustavi
country: Georgia
facility: JSC Rustavi Central Hospital
city: Tbilisi
country: Georgia
facility: LTD High Technology Medical Center University Clinic
city: Tbilisi
country: Georgia
facility: LTD Academician G. Chapidze Emergency Cardiology Center
city: Tbilisi
country: Georgia
facility: LTD Institute of Clinical Cardiology
city: Tbilisi
country: Georgia
facility: LTD Academician Vakhtang Bochorishvili Clinic
city: Tbilisi
country: Georgia
facility: LTD Central University Clinic After Academic N. Kipshidze
city: Tbilisi
country: Georgia
facility: LTD N 5 Clinikal Hospital
city: Regensburg
country: Germany
facility: University Hospital Regensburg, Department of Infectious Diseases
city: Athens
country: Greece
facility: "LAIKO" General Hospital, 1st Department of Internal Medicine
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Poriyya 'Illit
country: Israel
facility: The Baruch Padeh Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Safed
country: Israel
facility: Sieff Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Genoa
country: Italy
facility: IRCCS-University Hospital San Martino-IST, Infectious Diseases Division
city: Monza
country: Italy
facility: University of Milan-Bicocca- S.Gerardo Hospital
city: Trieste
country: Italy
facility: Giuliano Isontina University Health Authority
city: Udine
country: Italy
facility: Central Friuli University Healthcare Company
city: Guadalajara
country: Mexico
facility: Fray Antonio Alcalde Guadalajara Civil Hospital
city: Monterrey
country: Mexico
facility: Dr. Jose Eleuterio Gonzalez Monterrey University Hospital
city: Panamá
country: Panama
facility: INDICASAT SMO / Santo Tomas Hospital, Investigation Department
city: Belgorod
country: Russian Federation
facility: St. Joseph Belgorod Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Vinogradov Moscow Municipal Hospital, Department of Surgery #14
city: Moscow
country: Russian Federation
facility: N.I. Pirogov City Clinical Hospital #1
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "Central Clinical Hospital with Polyclinic" under the Presidential Executive Office of Russian Federation
city: Moscow
country: Russian Federation
facility: L.A. Vorokhobov City Clinical Hospital #67
city: Nizhny Novgorod
country: Russian Federation
facility: City Hospital #33
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk City Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Hospital
city: Belgrade
country: Serbia
facility: Zvezdara University Medical Center, Clinic of Internal Diseases, Clinical Department of Nephrology and Metabolic Disorders with Dialysis "Prof. dr Vasilije Jovanovic"
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac, Center for Anesthesia and Reanimation
city: Benoni
country: South Africa
facility: Worthwhile Clinical Trials, Lakeview Hospital
city: Tongaat
country: South Africa
facility: Mediclinic Victoria - Practice of R Moodley and MI Sarwan
city: Barcelona
country: Spain
facility: Hospital del Mar, Department of Intensive Care
city: Elche
country: Spain
facility: University Hospital de Elche, Infectious Diseases Unit
city: Madrid
country: Spain
facility: General University Hospital Gregorio Maranon, Infectious Diseases / Internal Medicine
city: Madrid
country: Spain
facility: University Hospital Ramon y Cajal, Department of Infectious Diseases
city: Terrassa
country: Spain
facility: University Hospital Mutua de Terrassa, Unit of Infectious Diseases
city: Istanbul
country: Turkey
facility: Istanbul Kartal Kosuyolu Yuksek Ihtisas Training and Research Hospital
city: Samsun
country: Turkey
facility: Ondokuz Mayis University School of Medicine, Department of Infectious Diseases
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk I.I. Mechnykov Regional Clinical Hospital
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk City Multispecialty Clinical Hospital #4
city: Ivano-Frankivs'k
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: V.T. Zaitsev Institute of General and Emergency Surgery
city: Kharkiv
country: Ukraine
facility: Public Non-Profit Enterprise: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council
city: Vinnytsia
country: Ukraine
facility: Communal Nonprofit Enterprise "Vinnytsia Regional Clinical Hospital named after N.I. Pirogov Vinnytsia Regional Council"
city: Zaporizhzhya
country: Ukraine
facility: City Clinical Hospital #3
Study officials:
affiliation: Basilea Pharmaceutica
name: Marc Engelhardt, MD
role: STUDY_DIRECTOR
References:
citation: Hamed K, Engelhardt M, Jones ME, Saulay M, Holland TL, Seifert H, Fowler VG Jr. Ceftobiprole versus daptomycin in Staphylococcus aureus bacteremia: a novel protocol for a double-blind, Phase III trial. Future Microbiol. 2020 Jan;15(1):35-48. doi: 10.2217/fmb-2019-0332. Epub 2020 Jan 10.
citation: Holland TL, Cosgrove SE, Doernberg SB, Jenkins TC, Turner NA, Boucher HW, Pavlov O, Titov I, Kosulnykov S, Atanasov B, Poromanski I, Makhviladze M, Anderzhanova A, Stryjewski ME, Assadi Gehr M, Engelhardt M, Hamed K, Ionescu D, Jones M, Saulay M, Smart J, Seifert H, Fowler VG Jr; ERADICATE Study Group. Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia. N Engl J Med. 2023 Oct 12;389(15):1390-1401. doi: 10.1056/NEJMoa2300220. Epub 2023 Sep 27.