A Study of Ceftobiprole in Patients With Fever and Neutropenia.

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of ceftobiprole versus a comparator in patients with fever and neutropenia

Detailed Description
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This study is being discontinued due to issues regarding the comparator, cefepime. In Nov 2007 FDA issued a MedWatch regarding cefepime and the trial was suspended. As of May 14, 2008 the FDA was still evaluating the data on cefepime and final follow up is pending. There were no safety issues with ceftobiprole in this study based on the enrollment of 2 subjects in September of 2007. The study is being discontinued for administrative reasons. Ceftobiprole medocaril is a cephalosporin antibiotic with anti-MRSA (Methicillin-Resistant Staphylococcus Aureus) activity. Ceftobiprole is not yet approved, but undergoing regulatory review for treatment of skin infections. This is a randomized (patients are assigned to receive the different treatments under study based on chance), double-blind (neither the patient nor the physician knows whether the drug being investigated or the comparator agent is being taken), multicenter study of treatment with ceftobiprole medocaril versus treatment with a comparator in patients 18 years of age or older, who have fever and neutropenia after chemotherapy for cancer that requires intravenous therapy. Patients will be randomly assigned to receive either ceftobiprole medocaril or comparator. In addition, patients in the comparator group who are at risk of serious infections due to gram-positive pathogens (disease-causing bacteria) may also receive an antibiotic with MRSA activity. The study will consist of the following 3 phases: a prerandomization phase (includes screening and baseline assessments); a treatment phase, and a follow-up phase consisting of a primary efficacy visit and a late follow-up visit. The primary endpoint is the clinical cure rate. The total duration of of the study is determined by the time to resolution of fever and neutropenia and the conditions associated with the episode of fever and neutropenia. This is followed by the primary efficacy visit (7 to 10 days after the end of therapy) and the late follow-up visit (28 to 35 days after the end of treatment). Cultures (samples of blood or other suspected sites of infection) will be collected during the study as well as blood samples for hematology and chemistry (safety assessments). All adverse events will also be reported throughout the study and for about 4 to 5 weeks after the last dose of study drug. Patients will be randomized to either ceftobiprole or comparator for approximately 7 to 14 days.

Official Title
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Multicenter, Randomized, Double-Blind Study of Ceftobiprole Versus Comparators in the Treatment of Patients With Fever and Neutropenia

Conditions
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Fever, Neutropenia, Gram-positive Bacterial Infections, Pseudomonas Infection

Intervention / Treatment
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* Drug: Ceftobiprole Medocaril
* Drug: Cefepime with or without vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with neutropenia and fever associated with administration of chemotherapy for cancer that requires intravenous therapy with antibiotics. Exclusion Criteria: Patients who have received antibacterial (oral or intravenous ) treatment for more than 24 hours for fever and neutropenia or have received systemic antibacterial therapy in the previous 72 hours for a defined infectious disease Patients with known or suspected hypersensitivity to any related anti-infective patients with hepatic impairment Patients with severe renal impairment Patients who are pregnant or lactating Patients who are likely to require major surgical intervention for infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Ceftobiprole Medocaril 500 mg every 8 hours 120-minute infusion [250 mL] | Drug: Ceftobiprole Medocaril<br>* 500 mg every 8 hours<br>|
| Active Comparator: 002<br>Cefepime with or without vancomycin 2 g every 8 hrs-30 min infusion vancomycin 1 000mg every 12 hrs-60 min infusion | Drug: Cefepime with or without vancomycin<br>* 120-minute infusion [250 mL]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure Rate of Ceftobiprole vs Comparator in Patients With Fever and Neutropenia. | Clinical cure rate (the ratio of the number of clinically cured patients to the total number of patients in the population) at 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter. Cure without modification: A subject will be considered to be cured at the primary efficacy visit if: The subject's fever and clinical signs and symptoms are resolved to the extent that no further anti-infective therapy is necessary as determined by the investigator Any infecting organisms that were identified at baseline were eradicated | 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure Regardless of Modification of Therapy | 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 defined as addition of an anti-fungal agent and/or an aminoglycoside. Cure with modification: The subject requires antifungals, which will be considered a failure for the primary endpoint. The subject needs modification of study therapy by adding one or more agents (other than protocol-defined chemoprophylaxis antibiotics). | 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter. | 
| Clinical Success at 72 Hours | 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 | 72 hours after starting study drug | 
| Clinical Cure Without Prophylactic Antibiotics After the End-of-treatment (EOT) Visit up to 28 Days of Study Drug | 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 EOT visit. | 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low numbers of neutrophils in the blood, increased body temperature, cancer chemotherapy, ceftobiprole, pseudomonas infections