A Randomized, Double-Blind, Active-Controlled, Parallel-Group, Noninferiority, Multicenter Study of Ceftobiprole Medocaril Versus Cefepime With or Without Vancomycin in the Treatment of Subjects With Fever and Neutropenia Estudio aleatorizado, en doble ciego, controlado con producto activo, de grupos paralelos, de no inferioridad y multicéntrico, de ceftobiprol medocaril frente a cefepima con o sin vancomicina en el tratamiento de pacientes con fiebre y neutropenia

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2007-003464-22-ES
• Date of registration: 20/11/2007
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium
• Public title: A Randomized, Double-Blind, Active-Controlled, Parallel-Group, Noninferiority, Multicenter Study of Ceftobiprole Medocaril Versus Cefepime With or Without Vancomycin in the Treatment of Subjects With Fever and Neutropenia Estudio aleatorizado, en doble ciego, controlado con producto activo, de grupos paralelos, de no inferioridad y multicéntrico, de ceftobiprol medocaril frente a cefepima con o sin vancomicina en el tratamiento de pacientes con fiebre y neutropenia
• Scientific title: A Randomized, Double-Blind, Active-Controlled, Parallel-Group, Noninferiority, Multicenter Study of Ceftobiprole Medocaril Versus Cefepime With or Without Vancomycin in the Treatment of Subjects With Fever and Neutropenia Estudio aleatorizado, en doble ciego, controlado con producto activo, de grupos paralelos, de no inferioridad y multicéntrico, de ceftobiprol medocaril frente a cefepima con o sin vancomicina en el tratamiento de pacientes con fiebre y neutropenia
• Date of first enrolment: 03/01/2008
• Target sample size: 340
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003464-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: yes Placebo: Other:
• Phase: Human pharmacology (Phase I): Therapeutic exploratory (Phase II): Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV):

Countries of recruitment

Belgium, Hungary, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
General

Men or women 18 years of age or older

Women must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method [e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], contraceptive patch, or male partner sterilization) before entry and throughout the study; have a negative serum b-human chorionic gonadotropin (b-hCG) or urine pregnancy test (depending on local regulations) at screening.

Willing to adhere to the prohibitions and restrictions specified in this protocol.

Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Disease Specific

Neutropenia associated with administration of chemotherapy for cancer: absolute neutrophil count (ANC) <= 500 cells/mm³. Subjects with ANC <1,000 cells/mm³ within 48 hours after the onset of fever will be enrolled only if their ANC is expected to further decrease to <500 cells/mm³, based on clinical experience with the particular subject or the chemotherapeutic regimen used to treat the subject. If the subject’s ANC does not fall below 500 cells/mm³ within 48 hours of the onset of fever then the study drug should be discontinued.

Fever: single oral temperature (or equivalent) >=38.3°C (101°F) OR temperature of >=38.0°C (100.4°F) for at least 1 hour.

Require i.v. therapy for treatment of fever and neutropenia.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment.

Is pregnant or lactating.

Known or suspected hypersensitivity to any related anti-infective (including vancomycin, or b-lactam antibiotics such as penicillins and cephalosporins).

Require only oral antibacterial therapy to treat their fever and neutropenia.

Have received more than 24 hours of oral or i.v. antibacterial treatment for fever and neutropenia or have received systemic antibacterial therapy in the previous 72 hours for a defined infectious disease. (Note: Subjects receiving oral prophylaxis regimens will be eligible for enrollment provided this prophylaxis began before the onset of fever).

Hepatic impairment, defined as an increase to greater than 4 times the upper limits of normal for aspartate aminotransferase (AST) or ALT, or greater than twice the upper limit for bilirubin.

Severe renal impairment (CLCR <25 mL per minute) or require dialysis.

Isolation, in the last 14 days, of pathogenic bacteria resistant to either study drug therapy other than MR staphylococci.

Subjects who are moribund or who are unlikely to survive for at least 1 month.

Subjects with shock (systolic blood pressure <90 mmHg) unresponsive to fluid replacement.

Previously been entered into this study.

Poorly controlled seizure disorder.

Human immunodeficiency virus (HIV) infection.

Neutropenia syndromes that are not associated with chemotherapy for cancer (e.g., chronic benign neutropenia).

Suspected or established infective endocarditis, empyema, intra abdominal infection, lung abscess, pneumonia secondary to bronchial obstruction, meningitis, or osteomyelitis.

Complicated central venous catheter (CVC)-related infection (i.e., CVC infection associated with septic thrombosis, endocarditis, or osteomyelitis).

Likely to require major surgical intervention for infection (i.e., amputation of infected limb, perforation of bowel with secondary peritonitis).

Scheduled for or expected to receive granulocyte transfusions.

Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Sujetos de 18 años o más, con fiebre y neutropenia tras quimioterapia para cancer, que requieren tratamiento intravenoso para fiebre y neutropenia. Subjects 18 years of age or older with fever and neutropenia after chemotherapy for cancer, who require i.v. therapy for treatment of fever and neutropenia

Intervention(s)

Product Name: ceftobiprole medocaril
Product Code: JNJ-30982081
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: ceftobiprole medocaril
CAS Number: 252188-71-9
Current Sponsor code: JNJ-30982081
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Trade Name: Maxipime
Product Name: Maxipime (cefepime hydrochloride) 2g/vial powder for injection
Pharmaceutical Form: Powder for injection*
INN or Proposed INN: Cefepime
CAS Number: 88040-23-7
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Trade Name: ZENGAC
Product Name: ZENGAC (vancomycin hydrochloride) 1 g, powder for solution for injection and for oral solution
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: vancomycin
CAS Number: 1404-93-9
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Trade Name: Cepimex
Product Name: CEPIMEX (cefepime) 1000 mg/3mL powder and solvent for solution for injection
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: cefepime
CAS Number: 88040-23-7
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Clinical cure rate - as defined in the protocol, Clinical Efficacy is the ratio of the number of clinically cured subjects to the total number of subjects in the population under consideration, at the primary efficacy visit.

Main Objective: To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin in subjects with fever and neutropenia with regard to clinical cure versus not cured, after completing the initial course of therapy, without modification.

Secondary Objective: To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the initial course of therapy, regardless of modification of therapy.

To compare the clinical success rate (absence or improvement of signs and symptoms of infection) at 72 hours after starting ceftobiprole with that of cefepime with or without vancomycin.

To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the unmodified initial course of therapy, and receiving no prophylactic antibiotics after the end of treatment (EOT) visit.

Secondary ID(s)

CEFTOFBN3004

2007-003464-22-BE