Comparative Antibiotic Therapy for Subjects With Pulmonary Infiltrates in the ICU

Bacterial Infection Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00307099
• Other study ID #: 03-216
• Secondary ID: BAMSG 4-02
• Status: Terminated
• Phase: Phase 3
• First received: March 23, 2006
• Last updated: June 6, 2013
• Start date: October 2006
• Est. completion date: February 2007

Study information

• Verified date: February 2007
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 460
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Infection
• Bacterial Infections

Intervention

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.
• Standard antibiotic therapy
Standard intravenous antibiotic therapy for a minimum of 8 days.

Locations

Country	Name	City	State
United States	Akron General Medical Center- Medicine	Akron	Ohio
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Roswell Park Cancer Institute - Infectious Diseases	Buffalo	New York
United States	University of Miami	Miami	Florida
United States	Saint Patricks Hospital and Health Sciences Center	Missoula	Montana
United States	Christiana Care Health Services	Newark	Delaware
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	South Texas Veterans Health Care System	San Antonio	Texas
United States	Washington University in St. Louis	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Day 0 to day 28 (or hospital discharge, if earlier)	Yes
Secondary	ICU and Hospital length of stay (LOS)		Through Day 28 (or hospital discharge, if greater)	No
Secondary	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.		Through Day 28 (or hospital dischange, if greater)	No
Secondary	Any clinically significant infection, as determined by the subject's primary care team.		Through Day 28 (or hospital dischange, if greater)	Yes
Secondary	Mortality rates at Days 14 and 28.		Days 14 and 28.	Yes