Evaluation of Ceftaroline Fosamil Versus a Comparator in Adult Subjects With Community-acquired Bacterial Pneumonia (CABP) With Risk for Methicillin-resistant Staphylococcus Aureus

Infections Clinical Trial

Official title:

A Multicenter, Multinational, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Ceftaroline Fosamil Versus Ceftriaxone Plus Vancomycin in Adult Subjects With Community-acquired Bacterial Pneumonia at Risk for Infection Due to Methicillin-resistant Staphylococcus Aureus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01645735
• Other study ID #: P903-25
• Status: Completed
• Phase: Phase 4
• First received: July 9, 2012
• Last updated: December 24, 2015
• Start date: October 2012
• Est. completion date: December 2013

Study information

• Verified date: December 2015
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether ceftaroline is effective and safe for the treatment of patients with Community-acquired Bacterial Pneumonia (CABP) at risk for infection due to Methicillin-resistant Staphylococcus aureus (MRSA).

Description:

A Multicenter, Multinational, Randomized, Double-blind Study to Evaluate the Efficacy and safety of Ceftaroline fosamil Versus Ceftriaxone Plus Vancomycin in Adult Subjects with Community-acquired Bacterial Pneumonia at Risk for Infection Due to Methicillin-resistant Staphylococcus aureus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects are required to meet All of the following inclusion criteria:

1. Male or female, = 18 years old

2. Presence of CABP requiring hospitalization

3. Presence of CABP meeting the following criteria:

I. confirmed pneumonia (new or progressive pulmonary) II. Acute illness (= 7 days' duration) with at least 3 clinical signs or symptoms consistent with a lower respiratory tract infection

MRSA Risk Factors

• MRSA-positive blood culture or respiratory specimen or a risk factor for MRSA such as a history of colonization with MRSA

Exclusion Criteria:

• Subjects must Not meet any of the following exclusion criteria at baseline:

1. History of any hypersensitivity or allergic reaction to any ß-lactam antimicrobial

2. Suspected or microbiologically-documented infection with a pathogen known to be resistant to any of the study drugs

3. Non-infectious causes of pulmonary infiltrates (eg, pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure)

4. More than 24 hours of potentially effective systemic antibacterial therapy for CABP within 96 hours before randomization

5. End-stage renal disease [Creatinine Clearance (CrCl) < 15], including hemodialysis

6. Evidence of significant hepatic, hematological, or immunocompromising condition

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infection
• Infections
• Pneumonia
• Pneumonia, Bacterial
• Staphylococcal Infections

Intervention

Drug:
• Ceftaroline fosamil
Ceftaroline fosamil 600 mg IV over 60 minutes q8h; treatment duration 5 to 14 days
• Ceftriaxone plus vancomycin
Ceftriaxone 2g IV over 30 minutes q24h plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days

Locations

Country	Name	City	State
Georgia	Investigational Site	Tbilisi
Hungary	Investigational Site	Matrahaza
Poland	Investigational Site	Lodz
Poland	Investigational Site	Lublin
Poland	Investigational Site	Wilkowice-Bystra
Romania	Investigational Site	Bucharest
Romania	Investigational Site	Craiova	Dolj
Romania	Investigational Site	Iasi
Russian Federation	Investigational Site	Moscow
Russian Federation	Investigational Site	St. Petersburg
Russian Federation	Investigational Site	Yaroslavl
Spain	Investigational Site	Alicante
Spain	Investigational Site	Barcelona
Ukraine	Investigational Site	Dnipropetrovsk
Ukraine	Investigational Site	Ivano-Frankivsik
Ukraine	Investigational Site	Kharkiv
Ukraine	Investigational Site	Kyiv
Ukraine	Investigational Site	Zaporizhzhya
United States	Investigational Site	Chicago	Illinois
United States	Investigational Site	Columbus	Ohio
United States	Investigational Site	DeLand	Florida
United States	Investigational Site	Kansas City	Kansas
United States	Investigational Site	Laconia	New Hampshire
United States	Investigational Site	Lima	Ohio
United States	Investigational Site	Minneapolis	Minnesota
United States	Investigational Site	Oklahoma City	Oklahoma
United States	Investigational Site	Omaha	Nebraska
United States	Investigational Site	Phoenix	Arizona
United States	Investigational Site	Royal Oak	Michigan
United States	Investigational Site	St. Louis	Missouri
United States	Investigational Site	Sylmar	California

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	AstraZeneca

Countries where clinical trial is conducted

United States,  Georgia,  Hungary,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Microbiological Outcomes by Baseline Pathogen at TOC in the Microbiological Modified Intent-to-Treat (mMITT) Population	An overall microbiological outcome was derived based on the subject's baseline pathogen. As no follow-up specimens were collected at the TOC visit for any subjects, all microbiological outcomes were derived based strictly on clinical outcomes, as either presumed eradication (ie, source specimen was not available to culture and the subject was assessed as clinical cure) , presumed persistence (ie, source specimen was not available to culture and the subject was assessed as a clinical failure), or indeterminate (ie, source specimen was not available to culture and the subject's clinical response was assessed as indeterminate).	Test of Cure, an average of 3 weeks	No
Other	Safety Evaluation	Adverse events (AEs), serious adverse events (SAEs), deaths, discontinuation due to AEs	Baseline (Day 0) to Day 49	Yes
Primary	Clinical Response at Study Day 4 in the Modified Intent-to-Treat (MITT) Population	Clinical response was defined as meeting all of the following criteria: Symptom Improvement - Improvement in at least 2 and no worsening of any of the following symptoms compared to baseline: Cough; Dyspnea; Sputum production; Chest pain; Clinical Stability (per Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines; Mandell et al, 2007): Temperature = 37.8°C; Heart rate = 100 beats/min; Respiratory rate = 24 breaths/min; Systolic blood pressure = 90 mmHg; Oxygen saturation = 90%; Confusion/disorientation absent	Study Day 4	No
Primary	Clinical Outcome at Test of Cure (TOC) in the MITT Population	An assessment of clinical outcome was made by the Investigator at TOC. The clinical outcome categories were: Cure: Resolution of all acute signs and symptoms of CABP or improvement to such an extent that no further antimicrobial therapy was required; Failure: Subjects who meet either of the following criteria: Incomplete resolution or worsening of CABP signs and symptoms or development of new CABP signs or symptoms requiring alternative nonstudy antimicrobial therapy; Death in which CABP is contributory; Indeterminate: Study data are not available for evaluation of efficacy for any reason, including: Death in which CABP is clearly noncontributory; Lost to follow-up; Extenuating circumstances precluding classification as a cure or failure; A favorable clinical outcome at Test-of Cure (TOC) was clinical cure.	Test of Cure, an average of 3 weeks	No

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