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

• ClinicalTrials.gov Identifier: NCT01645735
• Recruitment Status: Completed
• First Posted: July 20, 2012
• Results First Posted: February 1, 2016
• Last Update Posted: February 1, 2016
• Sponsor: Forest Laboratories
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Forest Laboratories

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Infections	Drug: Ceftaroline fosamil; Drug: Ceftriaxone plus vancomycin	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 2012
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ceftaroline; Ceftaroline fosamil 600 mg Intravenous (IV) administration over 60 minutes, every 8 hours (q8h); dosing to be adjusted for renal function; treatment duration 5 to 14 days	Drug: Ceftaroline fosamil; Ceftaroline fosamil 600 mg IV over 60 minutes q8h; treatment duration 5 to 14 days; Other Names: Teflaro; PPI-0903; TAK-599; TAK599; PPI0903 Teflaro
Active Comparator: Ceftriaxone plus vancomycin; Ceftriaxone 2 g IV over 30 minutes once per day (q24h) plus vancomycin 15 mg/kg IV every 12 hours (q12h) initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days	Drug: 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

Outcome Measures

Primary Outcome Measures :

1. Clinical Response at Study Day 4 in the Modified Intent-to-Treat (MITT) Population [ Time Frame: Study Day 4 ]

   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
2. Clinical Outcome at Test of Cure (TOC) in the MITT Population [ Time Frame: Test of Cure, an average of 3 weeks ]

   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.

Other Outcome Measures:

1. Microbiological Outcomes by Baseline Pathogen at TOC in the Microbiological Modified Intent-to-Treat (mMITT) Population [ Time Frame: Test of Cure, an average of 3 weeks ]
   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).
2. Safety Evaluation [ Time Frame: Baseline (Day 0) to Day 49 ]
   Adverse events (AEs), serious adverse events (SAEs), deaths, discontinuation due to AEs

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 β-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

Contacts and Locations

Locations

United States, Arizona

Investigational Site

Phoenix, Arizona, United States, 85008

United States, California

Investigational Site

Sylmar, California, United States, 91342

United States, Florida

Investigational Site

DeLand, Florida, United States, 32720

United States, Illinois

Investigational Site

Chicago, Illinois, United States, 60611

United States, Kansas

Investigational Site

Kansas City, Kansas, United States, 66012

United States, Michigan

Investigational Site

Royal Oak, Michigan, United States, 48073

United States, Minnesota

Investigational Site

Minneapolis, Minnesota, United States, 55145

United States, Missouri

Investigational Site

St. Louis, Missouri, United States, 63110

United States, Nebraska

Investigational Site

Omaha, Nebraska, United States, 68131

United States, New Hampshire

Investigational Site

Laconia, New Hampshire, United States, 03246

United States, Ohio

Investigational Site

Columbus, Ohio, United States, 43215

Investigational Site

Lima, Ohio, United States, 45801

United States, Oklahoma

Investigational Site

Oklahoma City, Oklahoma, United States, 73104

Georgia

Investigational Site

Tbilisi, Georgia, 0144

Hungary

Investigational Site

Matrahaza, Hungary, 3233

Poland

Investigational Site

Lodz, Poland, 90-153

Investigational Site

Lublin, Poland, 20-954

Investigational Site

Wilkowice-Bystra, Poland, 43-365

Romania

Investigational Site

Craiova, Dolj, Romania, 200515

Investigational Site

Bucharest, Romania, 030303

Investigational Site

Iasi, Romania, 700115

Russian Federation

Investigational Site

Moscow, Russian Federation, 109240

Investigational Site

St. Petersburg, Russian Federation, 196247

Investigational Site

Yaroslavl, Russian Federation, 150003

Spain

Investigational Site

Alicante, Spain, 03010

Investigational Site

Barcelona, Spain, 08304

Ukraine

Investigational Site

Dnipropetrovsk, Ukraine, 49059

Investigational Site

Ivano-Frankivsik, Ukraine, 76018

Investigational Site

Kharkiv, Ukraine, 61115

Investigational Site

Kyiv, Ukraine, 03680

Investigational Site

Zaporizhzhya, Ukraine, 69035

Sponsors and Collaborators

Forest Laboratories

AstraZeneca

Investigators

• Study Director: Medical Monitor; Forest Laboratories Inc, an affiliate of Allergan plc

More Information

Additional Information:

Related Info 

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01645735
• Other Study ID Numbers: P903-25
• First Posted: July 20, 2012
• Results First Posted: February 1, 2016
• Last Update Posted: February 1, 2016
• Last Verified: December 2015

Keywords provided by Forest Laboratories:

Infections; Teflaro; cephalosporin; Ceftaroline; antibiotics; pneumonia

Additional relevant MeSH terms:

Infections; Pneumonia; Pneumonia, Bacterial; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Vancomycin; Ceftriaxone; Ceftaroline fosamil; Anti-Bacterial Agents; Anti-Infective Agents