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

NCT01110421 | Terminated Phase 3 Results DMC

• 3 other identifiers: CR016975DORIPED30032009-016069-27
• Study Type: interventional
• Target: 7
• Locations: 10 countries
• Sites: 25

Brief Summary

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

Conditions

Pneumonia, Bacterial; Community-Acquired Infections; Nosocomial Infection; Pneumonia, Ventilator-Associated

Keywords

Doripenem; Child, Hospitalized; Cefepime; Infusions, Intravenous; Severe community acquired pneumonia; Nosocomial pneumonia; Ventilator associated pneumonia

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit

  The participants were classified as cure if they had resolution or clinical improvement of signs and symptoms of pneumonia, favorable response at End of treatment for IV study (EIV) visit; had no fever; improvement or no progression of radiographic findings of pneumonia on chest X ray; improvement in oxygenation or discontinued mechanical ventilation in intubated participants; and not received nonstudy systemic antibacterial therapy for pneumonia.

  TOC (7 to 14 days after the last dose of study medication therapy)

Secondary Outcomes (6)

• The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit

  EIV (within 24 hours after completion of the last dose of IV study medication therapy)

• The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit

  LFU (28 to 42 days after the last dose of study medication therapy)

• The Number of Participants With Favorable Per-participant Microbiological Response Rate

  EIV (within 24 hours after completion of the last dose of IV study medication therapy), TOC (7 to 14 days after the last dose of study medication therapy), and LFU (28 to 42 days after the last dose of study medication therapy)

• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit

  EIV (within 24 hours after completion of the last dose of IV study medication therapy)

• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit

  TOC (7 to 14 days after the last dose of study medication therapy)

Study Arms (2)

Doripenem

EXPERIMENTAL

Doripenem 20 mg/kg per dose (up to 500 mg/dose) will be administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.

Drug: Cefepime placebo; Drug: Doripenem; Drug: Amoxicillin/clavulanate potassium

Cefepime

EXPERIMENTAL

Cefepime 50 mg/kg per dose (up to 2 g/dose) will be administered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefipime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.

Drug: Cefepime; Drug: Doripenem placebo; Drug: Amoxicillin/clavulanate potassium

Interventions

Cefepime placebo DRUG

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

Doripenem

Cefepime DRUG

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

Cefepime

Doripenem DRUG

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

Doripenem

Doripenem placebo DRUG

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

Cefepime

Amoxicillin/clavulanate potassium DRUG

Form=suspension or tablets, Route=oral (by mouth), may be administered at the discretion of the investigator once every 12 hours for up to 14 days following IV therapy with doripenem or cefepime.

Cefepime; Doripenem

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (25)

Unknown Facility

Little Rock, Arkansas, United States

Location

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Cleveland, Ohio, United States

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Toledo, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Loma Hermosa, Argentina

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Santa Fe, Argentina

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Belo Horizonte, Brazil

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Porto Alegre, Brazil

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São Paulo, Brazil

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Bogotá, Colombia

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Cali, Colombia

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Medellín, Colombia

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Riga, Latvia

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Kaunas, Lithuania

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Tauragė, Lithuania

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Vilnius, Lithuania

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Guadajalara, Mexico

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México, Mexico

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Monterrey, Mexico

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Zona, Panama

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Lublin, Poland

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Szczecin, Poland

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Kharkiv, Ukraine

Location

MeSH Terms

Conditions

Pneumonia, Bacterial; Community-Acquired Infections; Cross Infection; Pneumonia, Ventilator-Associated; Community-Acquired Pneumonia; Healthcare-Associated Pneumonia

Interventions

Cefepime; Doripenem; Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbapenems; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

This study was terminated early due to business reasons and not related to safety concerns or issues. As such, the limited enrollment precludes a meaningful conclusion about the efficacy and safety of doripenem compared with cefepime.

Results Point of Contact

• Title: Therapeutic Areas Director
• Organization: Janssen R&D US

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC C. Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2010
• First Posted: April 26, 2010
• Study Start: December 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: July 15, 2014
• Results First Posted: July 2, 2014

Record last verified: 2014-07

Locations

ME (3); US (4); AR (4); LI (3); BR (3); PL (2); PA (1); CO (3); LA (1); UA (1)