Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia

NCT03138733 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: BPR-CS-009
• Study Type: interventional
• Target: 390
• Locations: 17 countries
• Sites: 60

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).

Conditions

Staphylococcus Aureus Bacteremia

Keywords

Ceftobiprole, daptomycin, Staphylococcus aureus; Bacteremia, bloodstream infection

Outcome Measures

Primary Outcomes (1)

• 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): 1. Patient alive at Day 70 (± 5 days) post-randomization. 2. No new metastatic foci or complications of the SAB infection. 3. Resolution or improvement of SAB-related clinical signs and symptoms. 4. Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)

  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

  At PTE visit on Day 70 (± 5 days) post-randomization

• Number of Patients With Microbiological Eradication at the PTE Visit

  At PTE visit on Day 70 (± 5 days) post-randomization

• All-cause Mortality at the PTE Visit

  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

  Assessment after Day 7 post-randomization through to post-treatment evaluation (PTE) visit on Day 70 (± 5 days)

• Time to Staphylococcus Aureus Bloodstream Clearance

  Up to 6 weeks post-randomization

Study Arms (2)

Ceftobiprole medocaril

EXPERIMENTAL

Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril)

Drug: Ceftobiprole medocaril

Daptomycin

ACTIVE COMPARATOR

Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards), with or without aztreonam

Drug: Daptomycin

Interventions

Ceftobiprole medocaril DRUG

Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) as a 2 h infusion

Ceftobiprole medocaril

Daptomycin DRUG

Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Daptomycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Basilea Pharmaceutica: lead
• Department of Health and Human Services: collaborator

Study Sites (60)

eStudy Site - Chula Vista - PPDS

Chula Vista, California, 91911, United States

Location

Triple O Medical Services Inc

West Palm Beach, Florida, 33407, United States

Location

Mercury Street Medical Group

Butte, Montana, 59701, United States

Location

eStudy Site - Las Vegas - PPDS

Las Vegas, Nevada, 89109, United States

Location

Remington Davis Inc.

Columbus, Ohio, 43214, United States

Location

Central Hospital de San Isidro Melchor Posse

Buenos Aires, 81641, Argentina

Location

Medical Institute Platense SA

La Plata, B1900AVG, Argentina

Location

British Sanatorium SA

Rosario, S2000CVB, Argentina

Location

University Multiprofile Hospital for Active Treatment "Eurohospital Plovdiv", Plovdiv, Intensive Care Clinic

Plovdiv, 4004, Bulgaria

Location

University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of General, Purulent-Septic, Pediatric and One Day Surgery

Rousse, 7002, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Dr. Ivan Seliminski", Sliven, Anesthesiology and Intensive Care Department

Sliven, 8800, Bulgaria

Location

University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Clinic of Purulent-Septic Surgery

Sofia, 1606, Bulgaria

Location

De La Costa Clinic Ltd.

Barranquilla, 080020, Colombia

Location

JSC Rustavi Central Hospital

Rustavi, 3700, Georgia

Location

LTD High Technology Medical Center University Clinic

Tbilisi, 0144, Georgia

Location

LTD Academician G. Chapidze Emergency Cardiology Center

Tbilisi, 0159, Georgia

Location

LTD Institute of Clinical Cardiology

Tbilisi, 0159, Georgia

Location

LTD Academician Vakhtang Bochorishvili Clinic

Tbilisi, 0160, Georgia

Location

LTD Central University Clinic After Academic N. Kipshidze

Tbilisi, 0160, Georgia

Location

LTD N 5 Clinikal Hospital

Tbilisi, 0191, Georgia

Location

University Hospital Regensburg, Department of Infectious Diseases

Regensburg, 93053, Germany

Location

"LAIKO" General Hospital, 1st Department of Internal Medicine

Athens, 11527, Greece

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

The Baruch Padeh Medical Center

Poria Illit, 1520800, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5262000, Israel

Location

Sieff Medical Center

Safed, 1311001, Israel

Location

Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

IRCCS-University Hospital San Martino-IST, Infectious Diseases Division

Genoa, 16132, Italy

Location

University of Milan-Bicocca- S.Gerardo Hospital

Monza, 20900, Italy

Location

Giuliano Isontina University Health Authority

Trieste, 34125, Italy

Location

Central Friuli University Healthcare Company

Udine, 33100, Italy

Location

Fray Antonio Alcalde Guadalajara Civil Hospital

Guadalajara, 44280, Mexico

Location

Dr. Jose Eleuterio Gonzalez Monterrey University Hospital

Monterrey, 64460, Mexico

Location

INDICASAT SMO / Santo Tomas Hospital, Investigation Department

Panama City, 32401, Panama

Location

St. Joseph Belgorod Regional Clinical Hospital

Belgorod, 308007, Russia

Location

Vinogradov Moscow Municipal Hospital, Department of Surgery #14

Moscow, 117292, Russia

Location

N.I. Pirogov City Clinical Hospital #1

Moscow, 119049, Russia

Location

Federal State Budget Institution "Central Clinical Hospital with Polyclinic" under the Presidential Executive Office of Russian Federation

Moscow, 121359, Russia

Location

L.A. Vorokhobov City Clinical Hospital #67

Moscow, 123423, Russia

Location

City Hospital #33

Nizhny Novgorod, 603076, Russia

Location

Pyatigorsk City Clinical Hospital

Pyatigorsk, 357500, Russia

Location

Regional Clinical Hospital

Yaroslavl, 150062, Russia

Location

Zvezdara University Medical Center, Clinic of Internal Diseases, Clinical Department of Nephrology and Metabolic Disorders with Dialysis "Prof. dr Vasilije Jovanovic"

Belgrade, 11000, Serbia

Location

Clinical Center Kragujevac, Center for Anesthesia and Reanimation

Kragujevac, 34000, Serbia

Location

Worthwhile Clinical Trials, Lakeview Hospital

Benoni, 1501, South Africa

Location

Mediclinic Victoria - Practice of R Moodley and MI Sarwan

Tongaat, 4400, South Africa

Location

Hospital del Mar, Department of Intensive Care

Barcelona, 080003, Spain

Location

University Hospital de Elche, Infectious Diseases Unit

Elche, 03203, Spain

Location

General University Hospital Gregorio Maranon, Infectious Diseases / Internal Medicine

Madrid, 28007, Spain

Location

University Hospital Ramon y Cajal, Department of Infectious Diseases

Madrid, 28034, Spain

Location

University Hospital Mutua de Terrassa, Unit of Infectious Diseases

Terrassa, 08221, Spain

Location

Istanbul Kartal Kosuyolu Yuksek Ihtisas Training and Research Hospital

Istanbul, 34846, Turkey (Türkiye)

Location

Ondokuz Mayis University School of Medicine, Department of Infectious Diseases

Samsun, 55139, Turkey (Türkiye)

Location

Dnipropetrovsk I.I. Mechnykov Regional Clinical Hospital

Dnipro, 49027, Ukraine

Location

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipro, 49102, Ukraine

Location

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, 76008, Ukraine

Location

V.T. Zaitsev Institute of General and Emergency Surgery

Kharkiv, 61018, Ukraine

Location

Public Non-Profit Enterprise: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council

Kharkiv, 61037, Ukraine

Location

Communal Nonprofit Enterprise "Vinnytsia Regional Clinical Hospital named after N.I. Pirogov Vinnytsia Regional Council"

Vinnytsia, 21018, Ukraine

Location

City Clinical Hospital #3

Zaporizhzhya, 69032, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 31918579 BACKGROUND

• 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.

  PMID: 37754204 RESULT

MeSH Terms

Conditions

Staphylococcal Infections; Bacteremia; Sepsis

Interventions

ceftobiprole medocaril; Daptomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr Marc Engelhardt, MD
• Organization: Basilea Pharmaceutica

marc.engelhardt@basilea.com

+41 79 701 0551

Study Officials

• Marc Engelhardt, MD

  Basilea Pharmaceutica

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 3, 2017
• Study Start: August 26, 2018
• Primary Completion: March 11, 2022
• Study Completion: March 11, 2022
• Last Updated: November 8, 2023
• Results First Posted: May 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); PA (1); GE (7); ZA (2); TU (2); IL (5); GR (1); UA (7); IT (4); RU (8); BU (4); SE (2); AR (3); CO (1); DE (1); ME (2); US (5)