Comparative Antibiotic Therapy for Subjects With Pulmonary Infiltrates in the ICU

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00307099
First received: March 23, 2006
Last updated: June 6, 2013
Last verified: February 2007
  Purpose

This study will enroll 460 subjects who have new pulmonary infiltrates during their ICU stay and who are at low risk of having pneumonia, as determined using the Clinical Pulmonary Infection Score (CPIS). The study is designed to determine whether 3 days of antibiotic treatment with meropenem (with or without coverage for MRSA) for ICU subjects diagnosed with new pulmonary infiltrates can reduce the emergence of anti-microbial-resistant organisms and the isolation of a potential pathogen compared to a standard course of antibiotic therapy (minimum of 8 days of therapy with antibiotics of the primary care team's choosing). Subjects will be randomly placed in either the meropenem group or standard antibiotic therapy group. The study will also examine whether short-course therapy reduces hospital length of stay and hospital cost, without having a negative effect on subject morbidity and mortality.


Condition Intervention Phase
Bacterial Infection
Drug: Meropenem
Drug: Standard antibiotic therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Multi-Center, Comparative Trial of Short-Course Empiric Antibiotic Therapy Versus Standard Antibiotic Therapy for Subjects With Pulmonary Infiltrates in the Intensive Care Unit (ICU): Impact on Antimicrobial Resistance, Superinfections, Length of ICU Stay and Hospitalization, and Mortality

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Combined measure of either emergence of antimicrobial resistance or isolation of a potential pathogen detected in any positive clinical cultures that are deemed a clinically significant infection [ Time Frame: Day 0 to day 28 (or hospital discharge, if earlier) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • ICU and Hospital length of stay (LOS) [ Time Frame: Through Day 28 (or hospital discharge, if greater) ] [ Designated as safety issue: No ]
  • Health Economics: The costs will be based on ICU LOS, hospital LOS, antibiotic treatment, and standardized costs related to the treatment of infection-related adverse experiences. [ Time Frame: Through Day 28 (or hospital dischange, if greater) ] [ Designated as safety issue: No ]
  • Any clinically significant infection, as determined by the subject's primary care team. [ Time Frame: Through Day 28 (or hospital dischange, if greater) ] [ Designated as safety issue: Yes ]
  • Mortality rates at Days 14 and 28. [ Time Frame: Days 14 and 28. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 460
Study Start Date: October 2006
Study Completion Date: February 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Meropenem
Meropenem 1 gram intravenously every 8 hours for 3 days (9 doses), then an additional 5 days if the Clinical Pulmonary Infection Score is greater than 6.
Drug: Meropenem
Meropenem 1 gram intravenously every 8 hours for 3 days (9 doses), then an additional 5 days if the Clinical Pulmonary Infection Score is greater than 6.
Active Comparator: Standard antibiotic therapy
Standard intravenous antibiotic therapy for a minimum of 8 days.
Drug: Standard antibiotic therapy
Standard intravenous antibiotic therapy for a minimum of 8 days.

Detailed Description:

Intensive care units (ICUs) are the most frequently identified source of nosocomial infections within the hospital, with infection rates and antimicrobial resistance rates significantly higher than in the general ward. In one study, antimicrobial use was reported to be 10 times higher in the ICU compared to antimicrobial use in the general ward. Although antibiotics are given for a variety of conditions, antibiotics prescribed for respiratory infections, suspected or proven, account for almost one-half of all antibiotic consumption in the ICU. Importantly, the use of antimicrobial agents has been identified as a critical risk factor in the emergence of resistant bacterial infections. By identifying and focusing on subsets of subjects who are unlikely to have infection and therefore unlikely to benefit from antibiotics, antibiotic use and the subsequent emergence of antimicrobial-resistant organisms could be limited. This is a Phase III, multi-center, randomized, open-label study designed to determine whether 3 days of antibiotic treatment with meropenem (with or without coverage for MRSA) for ICU subjects diagnosed with new pulmonary infiltrates can reduce the emergence of antimicrobial-resistant organisms and the isolation of a potential pathogen compared to a standard course of antibiotic therapy (minimum of 8 days of therapy with antibiotics of the primary care team's choosing). The primary objective of this study is to compare risk of resistant infection in the ICU by evaluating the difference in the incidence of either the emergence of antimicrobial-resistant bacteria or the isolation of a potential pathogen in ICU subjects who receive short-course empiric antibiotic therapy to ICU subjects who receive standard antibiotic therapy for the treatment of pulmonary infiltrates (with low likelihood of having pneumonia). Secondary objectives are to: 1) assess the mortality of subjects receiving short-course empiric antibiotic therapy compared to standard antibiotic therapy; 2) assess the ICU length of stay (LOS) in subjects receiving short-course empiric antibiotic therapy compared to standard antibiotic therapy; 3) assess the hospital LOS in subjects receiving short-course empiric antibiotic therapy compared to standard antibiotic therapy; 4) assess the costs of antibiotic therapy in subjects receiving short-course empiric antibiotic therapy compared to standard antibiotic therapy. The costs will be based on ICU LOS, hospital LOS, antibiotic treatment, and standard costs related to the treatment of infection-related adverse experiences; 5) assess the risk of clinically significant infection in subjects receiving short-course empiric antibiotic therapy compared to standard antibiotic therapy. This study will enroll 460 subjects who have new pulmonary infiltrates during their ICU stay and who are at low risk of having pneumonia, as determined using the Clinical Pulmonary Infection Score (CPIS).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject, or legal representative, has given written informed consent.
  2. Subject has developed a new pulmonary infiltrate after ICU admission (confirmed by radiology).
  3. Subject has been hospitalized at least three days.
  4. CPIS </= 6.
  5. 18 years of age or older.

Exclusion Criteria:

  1. Burn patients.
  2. Cystic fibrosis patients.
  3. Bone marrow or solid organ transplant patients.
  4. Neutropenia from any cause (absolute neutophil count (ANC) </= 500) or likely to become neutropenic within 7 days,
  5. Known or suspected Human Immunodeficiency Virus (HIV) infection (HIV test is not required).
  6. Suspected or proven extrapulmonary infection site requiring antibiotic therapy.
  7. History of anaphylaxis to penicillin or cephalosporins.
  8. History of anaphylaxis to meropenem (any component of the formulation) or other carbapenem (e.g., imipenem).
  9. On systemic antibiotics for more than 7 consecutive days during the previous 30 days.
  10. Received more than 2 doses of systemic antibiotics within the past 24 hours (other than those used for surgical prophylaxis),

9. Pregnant or lactating (Women of childbearing potential must have a negative serum or urine pregnancy test within the 7 days prior to the first dose of antibiotics).

10. Unlikely to survive past Day 7 of the study (as determined by the primary care team).

11. Previous enrollment in this study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00307099

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-0006
United States, Delaware
Christiana Care Health Services
Newark, Delaware, United States, 19718-2200
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Missouri
Washington University in St. Louis
St. Louis, Missouri, United States, 63110
United States, Montana
Saint Patricks Hospital and Health Sciences Center
Missoula, Montana, United States, 59802-4008
United States, New York
Roswell Park Cancer Institute - Infectious Diseases
Buffalo, New York, United States, 14263-0001
United States, Ohio
Akron General Medical Center- Medicine
Akron, Ohio, United States, 44307-2433
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
South Texas Veterans Health Care System
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00307099     History of Changes
Other Study ID Numbers: 03-216, BAMSG 4-02
Study First Received: March 23, 2006
Last Updated: June 6, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
bacterial diseases

Additional relevant MeSH terms:
Bacterial Infections
Anti-Bacterial Agents
Meropenem
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents

ClinicalTrials.gov processed this record on September 18, 2014