A Safety and Tolerability Study of Doripenem Compared With Cefepime in Hospitalized Children With Bacterial Pneumonia

This study has been terminated.
(Trial terminated early per business decision)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01110421
First received: April 15, 2010
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the safety and tolerability of doripenem compared to cefepime in children hospitalized with pneumonia.


Condition Intervention Phase
Pneumonia, Bacterial
Community-Acquired Infections
Nosocomial Infection
Pneumonia, Ventilator-Associated
Drug: cefepime placebo
Drug: cefepime
Drug: doripenem
Drug: doripenem placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-Blind, Multicenter Study to Establish the Safety and Tolerability of Doripenem Compared With Cefepime in Hospitalized Children With Bacterial Pneumonia

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Adverse events, changes in [ Time Frame: Baseline up to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]
  • Clinical laboratory tests [ Time Frame: Baseline up to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]
  • Vital signs measurements [ Time Frame: Baseline up to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the clinical cure rate of doripenem compared with that of cefepime at the test of cure (TOC) visit [ Time Frame: 7 to 14 days after the last dose of iv study drug including oral antibiotic therapy ] [ Designated as safety issue: No ]
  • To determine the clinical improvement rate of doripenem compared with that of cefepime at the end of treatment for IV study drug therapy (EIV) visit [ Time Frame: Within 24 hours after completion of the last dose of iv study drug. ] [ Designated as safety issue: No ]
  • To determine the clinical relapse rate of doripenem compared with that of cefepime at the late follow-up (LFU) visit [ Time Frame: 28 to 42 days after the last dose of iv study drug including oral antibiotic therapy ] [ Designated as safety issue: No ]
  • To characterize the pharmacokinetics of doripenem in hospitalized children with pneumonia based on a sparse pharmacokinetic sampling scheme [ Time Frame: 1, 2, 4 and 6 hours after the 4th, 5th, 6th, or 7th dose administrations of doripenem/doripenem placebo ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: December 2010
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cefepime placebo/Doripenem
Patients will receive at least 3 days of iv doripenem administered every 8 hours immediately after each iv infusion of cefepime placebo for up to 14 days.
Drug: cefepime placebo
Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem for up to 14 days
Drug: doripenem
Type=once every 8 hours infused over 60 minutes, Unit=mg, Number=20mg/kg up to 500mg/dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv doripenem administered every 8 hours immediately after each iv infusion of cefepime placebo for up to 14 days
Experimental: Cefepime/ Doripenem placebo
Patients will receive at least 3 days of iv cefepime administered every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem placebo for up to 14 days.
Drug: cefepime
Type=once every 8 hours, Unit=mg, Number=50 mg/kg up to 2g/dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv cefepime administered every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem placebo for up to 14 days
Drug: doripenem placebo
Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately following each iv infusion of cefepime for up to 14 days

Detailed Description:

This is a randomized (study assigned by chance), double-blind (neither physician nor patient knows the name of the assigned study drugs), double-dummy (all patients will be given both a placebo [salt solution] and study drug in alternating periods of time during the study), active comparator-controlled (compare the 'test' treatment to standard-of-care therapy), multinational, multicenter study to establish the safety and tolerability of doripenem (an antibiotic) compared with cefepime (an antibiotic) administered by intravenous (iv) infusion (slow injection of drug solution into the vein over a period of time) in children ages 3 months to less than 18 years hospitalized with pneumonia (includes nosocomial pneumonia [NP], severe community-acquired pneumonia (CAP), and ventilator-assisted pneumonia [VAP]). The study includes 3 periods: a pretreatment (screening) period that will occur within 2 days prior to randomization (assignment of study drug); a treatment period of 10 to 14 days where patients will receive study drug treatment, and a posttreatment period consisting of 2 study visits. The maximum duration of study drug therapy is 14 days. The total duration of the study is approximately 7 to 8 weeks for each patient. The primary outcome measure in the study is safety and tolerability. Safety and tolerability will be evaluated by examining the incidence, severity, and type of adverse events, changes in clinical laboratory tests, vital signs measurements, and findings from physical examinations observed during treatment and at each posttreatment visit. An independent monitoring committee (IDMC) will be established for this study to ensure that the safety of the patients is not compromised. The IDMC will consist of individuals who are not associated with the conduct of the study, and will include but will not be limited to individuals with expertise relevant to the care of pediatric patients, and including at least one infectious disease physician and at least one statistician. Patients will receive IV Doripenem (20 mg/kg up to a maximum of 500 mg/dose) and cefepime placebo OR cefepime (50 mg/kg up to a maximum of 2 grams/dose and doripenem placebo once every 8 hours for up to 14 days. After receiving a minimum of 3 days of IV study drug therapy, patients may be switched to the oral antibiotic (amoxicillin/clavulanate potassium suspension or tablets) or an approved alternative oral agent to complete a total 10-14 days course of antibiotics.

  Eligibility

Ages Eligible for Study:   3 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Require parenteral antibacterial therapy for the treatment of pneumonia
  • Have new or progressive radiographic infiltrate(s) (alveolar, lobar, or consolidation) consistent with a bacterial pneumonia that is not related to cardiac or other disease processes
  • Must, based on the judgment of the investigator, require hospitalization initially and antibacterial therapy for 10 to 14 days for the treatment of the current pneumonia. (Note that the patient must require at least 3 days of IV antibiotic therapy initially)
  • Have a diagnosis of nosocomial pneumonia , severe community-acquired pneumonia, or ventilator-associated pneumonia, defined by the disease-specific criteria as stated in the study protocol
  • Have a clinical presentation compatible with bacterial pneumonia( with fever or hypothermia AND leukocytosis OR leucopenia AND at least 2 of the following clinical signs or symptoms in non-intubated patients: cough, new onset of lower respiratory tract secretions (including change in character of secretions or increase in the quantity of secretions or suctioning requirements), auscultatory findings of pneumonia or consolidation (rales, rhonchi bronchial breath sounds, decreased breath sounds, wheezing, and egophony), dyspnea, increased work of breathing expressed as retractions, nasal flaring, or grunting, hypoxemia or oxygen saturation less than 90% on room air, and tachypnea

Exclusion Criteria:

  • Received more than 24 hours of systemic antibacterial therapy in the 48 hours before the start of the infusion of the first dose of study drug for the current episode of pneumonia
  • Known presence at randomization of pulmonary infection caused only by bacteria that is resistant to cefepime or doripenem (including methicillin resistant Staphylococcus aureus) or presence at baseline of pulmonary infection with Stenotrophomonas species, or Burkholderia cepacia
  • Has any of the following conditions at baseline that may interfere with the diagnosis or response to therapy: chest trauma with severe lung contusion, acute respiratory distress syndrome, empyema, flail chest (severe injury to the chest), history of active lung cancer, chronic bronchitis with an exacerbation within the last 30 days, bronchiectasis (an obstructive lung disease), lung abscess(s), anatomical bronchial obstruction, active pulmonary tuberculosis with treatment, suspected pulmonary tuberculosis, suspected or documented atypical viral pneumonia without bacterial superinfection, suspected or documented pertussis, chemical pneumonitis (eg, aspiration of gastric contents, inhalation injury), or cystic fibrosis
  • The patient has any of the following clinically significant laboratory abnormalities: hematocrit of less than 20%
  • absolute neutrophil count (ANC) <500 cells/microL, platelet count <40,000 cells/microL, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin >5x the age specific upper limit of normal, acute or chronic renal insufficiency with a baseline creatinine clearance of <60 mL/minute or requires dialysis therapy for any reason, or are profoundly immunodeficient and require prophylactic antimicrobial therapy for Pneumocystis jirovicei, Toxoplasma gondii, or herpes viruses, and/or chronic or intermittent immunoglobin replacement therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01110421

Locations
United States, Arkansas
Little Rock, Arkansas, United States
United States, Ohio
Cleveland, Ohio, United States
Toledo, Ohio, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
Argentina
Buenos Aires, Argentina
Buenos Aires N/A, Argentina
Córdoba, Argentina
Loma Hermosa N/A, Argentina
Santa Fe, Argentina
Brazil
Belo Horizonte, Brazil
Porto Alegre, Brazil
São Paulo, Brazil
Colombia
Bogota, Colombia
Cali, Colombia
Medellin, Colombia
Latvia
Riga, Latvia
Lithuania
Kaunas, Lithuania
Taurage, Lithuania
Vilnius, Lithuania
Mexico
Guadajalara, Mexico
Mexico, Mexico
Monterrey, Mexico
Panama
Zona, Panama
Poland
Lublin, Poland
Szczecin, Poland
Ukraine
Kharkiv, Ukraine
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01110421     History of Changes
Other Study ID Numbers: CR016975, DORIPED3003, 2009-016069-27
Study First Received: April 15, 2010
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Latvia: State Agency of Medicines
Ukraine: State Pharmacological Center - Ministry of Health
United States: Federal Government

Keywords provided by Janssen Research & Development, LLC:
Doripenem
Child, Hospitalized
Cefepime
Infusions, Intravenous
Severe community acquired pneumonia
Nosocomial pneumonia
Ventilator associated pneumonia

Additional relevant MeSH terms:
Pneumonia, Bacterial
Pneumonia
Cross Infection
Community-Acquired Infections
Pneumonia, Ventilator-Associated
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Infection
Ventilator-Induced Lung Injury
Lung Injury
Cefepime
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014