Ceftobiprole in the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infections

NCT03137173 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: BPR-CS-008
• Study Type: interventional
• Target: 679
• Locations: 4 countries
• Sites: 34

Brief Summary

This was a randomized, double-blind, active-controlled, parallel-group, multicenter study in adult hospitalized patients to establish the safety and efficacy of ceftobiprole medocaril compared with vancomycin plus aztreonam in the treatment of acute bacterial skin and skin structure infections (ABSSSIs).

Conditions

Acute Bacterial Skin and Skin Structure Infections

Outcome Measures

Primary Outcomes (1)

• Early Clinical Response

  Comparison of early clinical response, including ≥ 20% reduction from baseline in the primary lesion area (based on ruler measurements), survival for ≥ 72 hours and no rescue therapy in the ITT population

  48-72 hours after start of study drug treatment

Secondary Outcomes (2)

• Investigator-assessed Clinical Success in the ITT Population

  15-22 days after randomization

• Investigator-assessed Clinical Success in the Clinically Evaluable (CE) Population

  15-22 days after randomization

Study Arms (2)

ceftobiprole medocaril

EXPERIMENTAL

Patients treated with ceftobiprole medocaril 500 mg q8h (with dose adjustment for renal impairment).

Drug: ceftobiprole medocaril

vancomycin+aztreonam

ACTIVE COMPARATOR

Patients treated with vancomycin 1000 mg (or 15 mg/kg) q12h plus aztreonam 1000 mg q12h (both with dose adjustment for renal impairment).

Drug: vancomycin+aztreonam

Interventions

ceftobiprole medocaril DRUG

ceftobiprole 500 mg was to be administered every 8 hours as a 2-hour IV infusion (with dose adjustment for renal impairment). The treatment duration was for a minimum of 5 days and a maximum of 10 days. Treatment could be extended up to 14 days if in the investigator's opinion this was required, and the extension was approved by the sponsor's medical monitor.

Also known as: ceftobiprole

ceftobiprole medocaril

vancomycin+aztreonam DRUG

Vancomycin 1000 mg (or 15 mg/kg) was to be administered every 12 hours (with dose adjustment for renal impairment) as 2-hour IV infusion. Vancomycin dose adjustment for morbidly obese and hypermetabolic patients was to be done according to local standard of care. When locally available, vancomycin trough testing (VTT) might have been used by the unblinded pharmacist or delegate to adjust the vancomycin dose. The treatment duration was for a minimum of 5 days and a maximum of 10 days. Treatment could be extended up to 14 days if in the investigator's opinion this was required, and the extension was approved by the sponsor's medical monitor. Aztreonam 1000 mg was to be administered as a 0.5-hour IV infusion every 12 hours. If CLCR was \< 30 mL/min (i.e., severe renal impairment), the aztreonam dosage regimen was to be adjusted. The requirement to continue aztreonam therapy beyond Day 3 was to be reassessed at the 72-hour study visit.

vancomycin+aztreonam

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, aged ≥18 years.
• Diagnosis of ABSSSI, meeting at least one of the definitions in (a) to (c) below. Local symptoms must have started within the 7 days prior to the Screening visit:
• Cellulitis/erysipelas, defined as a diffuse skin infection characterized by all of the following within 24 hours:
• i. Rapidly spreading areas of erythema, edema, and/or induration with a minimum total lesion surface area of 75cm\^2
• ii. No collection of pus apparent upon visual examination
• iii. At least two of the following local signs of infection:
• erythema
• induration
• localized warmth
• pain or tenderness on palpation
• swelling/edema
• Major cutaneous abscess, defined as infection characterized by a collection of pus within the dermis or deeper that is apparent upon visual examination before or after therapeutic intervention and is accompanied by all of the following within 24 hours:
• i. Erythema, edema and/or induration with a minimum total lesion surface area of 75 cm\^2.
• ii. At least two of the following local signs of infection:
• fluctuance

You may not qualify if:

• Patients meeting any one of the following:
• Use of any systemic antibacterial treatment within 14 days, or topical antibacterial administration on the primary lesion within 96 hours, before first infusion of study drug.
• Exception: Receipt of a single dose of a short acting (half-life ≤ 12 hours) antibacterial therapy (e.g., for surgical prophylaxis) within \> 3 days before randomization (i.e., patients cannot have received any antibacterial treatment within 72 hours of randomization).
• Contraindication to the administration of either of the study treatments, including known clinically-relevant hypersensitivity to related antibacterial treatments (e.g., beta-lactam and glycopeptide antibiotics), or to metronidazole if required as adjunctive therapy.
• Participation in any other clinical study within the 30 days prior to randomization, or any prior participation in this study.
• The primary ABSSSI is an uncomplicated skin and skin structure infection, such as furuncles, minor abscesses (area of suppuration not surrounded by cellulitis/erysipelas), impetiginous lesions, superficial or limited cellulitis/erysipelas, or minor wound infections (e.g., stitch abscesses).
• The primary ABSSSI is due to, or associated with, any of the following:
• Diabetic foot infection, gangrene, or perianal abscess.
• Concomitant infection at another site (e.g., septic arthritis, endocarditis, osteomyelitis), not including a secondary ABSSSI lesion.
• Infected burns.
• Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous).
• Any evolving necrotizing process (e.g., necrotizing fasciitis).
• Infections at vascular catheter sites, or involving thrombophlebitis.
• The primary ABSSSI is associated with, or in close proximity to, a prosthetic device.
• Patients who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI.

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (34)

Physician Alliance Research Center

Anaheim, California, 92804, United States

Location

Saint Joseph's Clinical Research

Anaheim, California, 92804, United States

Location

eStudySite - Chula Vista - PPDS

Chula Vista, California, 91911, United States

Location

Central Valley Research LLC

Fresno, California, 93721, United States

Location

Marvel Clinical Research

Huntington Beach, California, 92647, United States

Location

eStudySite - La Mesa - PPDS

La Mesa, California, 91942, United States

Location

Omnibus Clinical Research

La Palma, California, 90623, United States

Location

Alliance Research LLC

Long Beach, California, 90813, United States

Location

Long Beach Clinical Trials

Long Beach, California, 90813, United States

Location

Central Valley Research, LLC

Modesto, California, 95350, United States

Location

Gonzalez MD and Aswad MD Health Services

Coral Gables, Florida, 33134, United States

Location

L&C Professional Medical Research Institute

Miami, Florida, 33144, United States

Location

Mercury Street Medical Group

Butte, Montana, 59701, United States

Location

eStudySite - Las Vegas - PPDS

Las Vegas, Nevada, 89109, United States

Location

Excel Clinical Research

Las Vegas, Nevada, 89109, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

University Multiprofile Hospital for Active Treatment

Pleven, 5800, Bulgaria

Location

University Multiprofile Hospital for Active Treatment

Plovdiv, 4004, Bulgaria

Location

University Multiprofile Hospital for Active Treatment

Rousse, 7002, Bulgaria

Location

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

Sofia, 1606, Bulgaria

Location

Kaposi Mor Teaching Hospital

Kaposvár, 7400, Hungary

Location

CRU Hungary Ltd.

Miskolc, 3529, Hungary

Location

University of SzegednAlbert Szent-Gyorgyi Clinical Center

Szeged, 6720, Hungary

Location

Csolnoky Ferenc Hospital

Veszprém, 8200, Hungary

Location

Dnipropetrovsk I.I. Mechnуkov Regional Clinical Hospital, Surgery Department #2

Dnipro, 49005, Ukraine

Location

Ivano-Frankivsk City Clinical Hospital Surgery 1

Ivano-Frankivsk, 76008, Ukraine

Location

Ivano-Frankivsk City Clinical Hospital General Surgery

Ivano-Frankivsk, 76018, Ukraine

Location

Kyiv City Clinical Hospital

Kyiv, 03110, Ukraine

Location

Public City Clinical Hospital of Emergency Medical Care

Lviv, 79000, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, 79059, Ukraine

Location

Central City Clinical Hospital

Uzhhorod, 88000, Ukraine

Location

Vinnytsia M.I. Pyrohov Regional Clinical Hospital

Vinnytsia, 21018, Ukraine

Location

Zaporizhia City Clinical Hospital of Urgent and Emergency Medical Care

Zaporizhia, 69000, Ukraine

Location

Central District Hospital

Zhytomyr, 12430, Ukraine

Location

Related Publications (2)

• Welte T, Scheeren TW, Overcash JS, Saulay M, Engelhardt M, Hamed K. Efficacy and safety of ceftobiprole in patients aged 65 years or older: a post hoc analysis of three Phase III studies. Future Microbiol. 2021 May;16:543-555. doi: 10.2217/fmb-2021-0042. Epub 2021 May 7.

  PMID: 33960817 DERIVED

• Overcash JS, Kim C, Keech R, Gumenchuk I, Ninov B, Gonzalez-Rojas Y, Waters M, Simeonov S, Engelhardt M, Saulay M, Ionescu D, Smart JI, Jones ME, Hamed KA. Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET). Clin Infect Dis. 2021 Oct 5;73(7):e1507-e1517. doi: 10.1093/cid/ciaa974.

  PMID: 32897367 DERIVED

MeSH Terms

Interventions

ceftobiprole medocaril; ceftobiprole

Results Point of Contact

• Title: Project Physician
• Organization: Basilea Pharmaceutica International Ltd.

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 2, 2017
• Study Start: February 19, 2018
• Primary Completion: April 22, 2019
• Study Completion: April 22, 2019
• Last Updated: May 12, 2023
• Results First Posted: May 18, 2020

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

UA (10); US (16); BU (4); HU (4)