Staphylococcus Aureus BacteremiaPhase 3NCT03138733
Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia
A Phase 3 study testing Ceftobiprole medocaril and Daptomycin in people with Staphylococcus Aureus Bacteremia, run by Basilea Pharmaceutica at 60 sites in 17 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Staphylococcus Aureus Bacteremia
- What is being tested?
- Ceftobiprole medocaril and Daptomycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 390 participants
- Where
- 60 sitesin 17 countries
- Study dates
- 26 Aug 2018to 11 Mar 2022
- Phase
- Phase 3
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 ≥ 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:
- fever (e.g.≥ 38 °C/100.4 °F measured orally)
- white blood cell count > 10,000 or < 4,000 cells/µL, or > 10% immature neutrophils (bands)
- tachycardia (heart rate > 90 bpm)
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- hypotension (systolic blood pressure < 90 mmHg)
- At least one of the following:
- SAB in patients undergoing chronic intermittent hemodialysis or peritoneal dialysis
- Persistent SAB
- Definite native-valve right-sided infective endocarditis by Modified Duke's Criteria
- Other forms of complicated SAB
- Osteomyelitis (including vertebral, sternal, or long-bone osteomyelitis)
- Epidural or cerebral abscess
- Other inclusion criteria have been applied
Who cannot join
- 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
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- Requirement for continuous renal-replacement therapy
- Women who are pregnant or nursing
- Other exclusion criteria have been applied
Trial locations and contacts
60 sites in 17 countries.
60 sites in 17 countries
Russia8 sites
St. Joseph Belgorod Regional Clinical Hospital
Belgorod, 308007
Vinogradov Moscow Municipal Hospital, Department of Surgery #14
Moscow, 117292
N.I. Pirogov City Clinical Hospital #1
Moscow, 119049
Federal State Budget Institution "Central Clinical Hospital with Polyclinic" under the Presidential Executive Office of Russian Federation
Moscow, 121359
L.A. Vorokhobov City Clinical Hospital #67
Moscow, 123423
City Hospital #33
Nizhny Novgorod, 603076
Pyatigorsk City Clinical Hospital
Pyatigorsk, 357500
Regional Clinical Hospital
Yaroslavl, 150062
Georgia7 sites
JSC Rustavi Central Hospital
Rustavi, 3700
LTD High Technology Medical Center University Clinic
Tbilisi, 0144
LTD Academician G. Chapidze Emergency Cardiology Center
Tbilisi, 0159
LTD Institute of Clinical Cardiology
Tbilisi, 0159
LTD Academician Vakhtang Bochorishvili Clinic
Tbilisi, 0160
LTD Central University Clinic After Academic N. Kipshidze
Tbilisi, 0160
LTD N 5 Clinikal Hospital
Tbilisi, 0191
Ukraine7 sites
Dnipropetrovsk I.I. Mechnykov Regional Clinical Hospital
Dnipro, 49027
Dnipropetrovsk City Multispecialty Clinical Hospital #4
Dnipro, 49102
Ivano-Frankivsk Regional Clinical Hospital
Ivano-Frankivsk, 76008
V.T. Zaitsev Institute of General and Emergency Surgery
Kharkiv, 61018
Public Non-Profit Enterprise: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council
Kharkiv, 61037
Communal Nonprofit Enterprise "Vinnytsia Regional Clinical Hospital named after N.I. Pirogov Vinnytsia Regional Council"
Vinnytsia, 21018
City Clinical Hospital #3
Zaporizhzhya, 69032
United States5 sites
Mercury Street Medical Group
Butte, Montana, 59701
eStudy Site - Chula Vista - PPDS
Chula Vista, California, 91911
Remington Davis Inc.
Columbus, Ohio, 43214
eStudy Site - Las Vegas - PPDS
Las Vegas, Nevada, 89109
Triple O Medical Services Inc
West Palm Beach, Florida, 33407
Israel5 sites
Bnai Zion Medical Center
Haifa, 31048
The Baruch Padeh Medical Center
Poria Illit, 1520800
Chaim Sheba Medical Center
Ramat Gan, 5262000
Sieff Medical Center
Safed, 1311001
Sourasky Medical Center
Tel Aviv, 64239
Spain5 sites
Hospital del Mar, Department of Intensive Care
Barcelona, 080003
University Hospital de Elche, Infectious Diseases Unit
Elche, 03203
General University Hospital Gregorio Maranon, Infectious Diseases / Internal Medicine
Madrid, 28007
University Hospital Ramon y Cajal, Department of Infectious Diseases
Madrid, 28034
University Hospital Mutua de Terrassa, Unit of Infectious Diseases
Terrassa, 08221
Bulgaria4 sites
University Multiprofile Hospital for Active Treatment "Eurohospital Plovdiv", Plovdiv, Intensive Care Clinic
Plovdiv, 4004
University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of General, Purulent-Septic, Pediatric and One Day Surgery
Rousse, 7002
Multiprofile Hospital for Active Treatment "Dr. Ivan Seliminski", Sliven, Anesthesiology and Intensive Care Department
Sliven, 8800
University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Clinic of Purulent-Septic Surgery
Sofia, 1606
Italy4 sites
IRCCS-University Hospital San Martino-IST, Infectious Diseases Division
Genoa, 16132
University of Milan-Bicocca- S.Gerardo Hospital
Monza, 20900
Giuliano Isontina University Health Authority
Trieste, 34125
Central Friuli University Healthcare Company
Udine, 33100
Argentina3 sites
Central Hospital de San Isidro Melchor Posse
Buenos Aires, 81641
Medical Institute Platense SA
La Plata, B1900AVG
British Sanatorium SA
Rosario, S2000CVB
Mexico2 sites
Fray Antonio Alcalde Guadalajara Civil Hospital
Guadalajara, 44280
Dr. Jose Eleuterio Gonzalez Monterrey University Hospital
Monterrey, 64460
Serbia2 sites
Zvezdara University Medical Center, Clinic of Internal Diseases, Clinical Department of Nephrology and Metabolic Disorders with Dialysis "Prof. dr Vasilije Jovanovic"
Belgrade, 11000
Clinical Center Kragujevac, Center for Anesthesia and Reanimation
Kragujevac, 34000
South Africa2 sites
Worthwhile Clinical Trials, Lakeview Hospital
Benoni, 1501
Mediclinic Victoria - Practice of R Moodley and MI Sarwan
Tongaat, 4400
Turkey (Türkiye)2 sites
Istanbul Kartal Kosuyolu Yuksek Ihtisas Training and Research Hospital
Istanbul, 34846
Ondokuz Mayis University School of Medicine, Department of Infectious Diseases
Samsun, 55139
Germany1 site
University Hospital Regensburg, Department of Infectious Diseases
Regensburg, 93053
Greece1 site
"LAIKO" General Hospital, 1st Department of Internal Medicine
Athens, 11527
Panama1 site
INDICASAT SMO / Santo Tomas Hospital, Investigation Department
Panama City, 32401
About this study
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
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).
Read the 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:
- Screening assessments of up to 72 hours prior to randomization
- Randomization and subsequent active treatment with intravenous (i.v.) study drug (ceftobiprole or daptomycin ± aztreonam).
- 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.
- Conditions
- Staphylococcus Aureus Bacteremia
- Being tested
- Ceftobiprole medocaril, Daptomycin
- Keywords
- Ceftobiprole, daptomycin, Staphylococcus aureus, Bacteremia, bloodstream infection
- Medical subject headings
- Staphylococcal Infections, Bacteremia, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftobiprole medocarilDrug
Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) as a 2 h infusion
DaptomycinDrug
Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam
| Study group | Role | What they receive |
|---|---|---|
| Ceftobiprole medocaril | Experimental | Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Receives: Drug: Ceftobiprole medocaril |
| Daptomycin | Active comparator | Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards), with or without aztreonam Receives: Drug: Daptomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With or Without Overall Success at the Post-treatment Evaluation (PTE) Visit
Comparison of overall success rates in the mITT population
Overall success at PTE for the mITT population was defined as all of the following criteria being met (Responder):
- Patient alive at Day 70 (± 5 days) post-randomization.
- No new metastatic foci or complications of the SAB infection.
- Resolution or improvement of SAB-related clinical signs and symptoms.
- Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)
Measured: PTE visit on Day 70 (± 5 days) post-randomization
Secondary outcomes (6)
Number of Patients With or Without Overall Success at the PTE Visit in the CE Population
Comparison of overall success rates in the Clinical Evaluable (CE) population
Overall success at PTE for the CE population was defined as all of the following criteria being met (Responder):
- Patient alive at Day 70 (± 5 days) post-randomization.
- No new metastatic foci or complications of the SAB infection.
- Resolution or improvement of SAB-related clinical signs and symptoms.
- Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)
Measured: At PTE visit on Day 70 (± 5 days) post-randomization
Number of Patients With Microbiological Eradication at the PTE Visit
Comparison of microbiological eradication rates in the mITT population. Microbiological eradication rate was defined as a negative blood culture for S. aureus during study treatment and another negative blood culture during the follow up period up to PTE.
Measured: At PTE visit on Day 70 (± 5 days) post-randomization
All-cause Mortality at the PTE Visit
Comparison of all-cause mortality rates in the mITT population
Measured: At PTE visit on Day 70 (± 5 days) post-randomization
Number of Patients With or Without New Metastatic Foci or Other Complications of SAB Developed After Day 7
Comparison of complication rates in the mITT population defined by number of patients with development of new metastatic foci or other complications of SAB after Day 7
Measured: Assessment after Day 7 post-randomization through to post-treatment evaluation (PTE) visit on Day 70 (± 5 days)
Time to Staphylococcus Aureus Bloodstream Clearance
Time-to-event in the mITT Bloodstream clearance was defined as two consecutive study days with blood-culture-negative assessments for S. aureus, without any subsequent S. aureus relapse or reinfection
Measured: Up to 6 weeks post-randomization
Number of Patients With or Without Adverse Events (AEs)
Treatment-emergent adverse events in the safety population
Measured: AEs were assessed from the first dose of study drug through the post-treatment evaluation (PTE) visit on Day 70 (± 5 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2017
- Study start26 Aug 2018
- Primary completion11 Mar 2022
- Study completion11 Mar 2022
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 (2)Papers the sponsor has linked to this study.
- Other trials for Staphylococcus Aureus BacteremiaStudies 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
- 390 participants (actual)
Sponsor and investigators
- Lead sponsor
- Basilea Pharmaceutica
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biomedical Advanced Research and Development Authority
- Responsible party
- Sponsor
- Investigators
- Marc Engelhardt, MD, Study director, Basilea Pharmaceutica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03138733
- Sponsor's protocol ID
- BPR-CS-009
- Other IDs
- HHSO100201600002C
- Status last verified
- Sep 2026
- First submitted
- 27 Apr 2017
- Last updated
- 7 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31918579Holland 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.
PubMed 37754204