Clinical Trial: Rapid Empiric Treatment With Oseltamivir Study (RETOS)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Title: Effectiveness of Empiric Antiviral Treatment for Hospitalized Community Acquired Pneumonia During the Influenza Season (U18)

Brief Summary:

Current guidelines recommend early initiation of empiric antibiotic therapy to cover typical and atypical bacteria that may cause community-acquired pneumonia (CAP). Influenza antiviral therapy in patients with suspected or confirmed influenza. However, many clinicians do not suspect influenza among patients with CAP or other acute lower respiratory tract illness (LRTI) and often do not test for influenza. Additionally, results from currently available diagnostic tests for influenza may be delayed and several tests have low sensitivity and will give false negative results. Thus, anti-influenza treatment for patients with hospitalized influenza CAP and LRTI is frequently initiated late if at all. There is an association between delayed time to administration of empiric antibiotic therapy with increased clinical failure and mortality. As a result, empiric antibiotic therapy for patients with suspect CAP is begun within 4 - 6 hours of hospitalization. This has recently been demonstrated for delayed antiviral treatment as well. We hypothesize that, as happens with early empiric antibiotics for bacterial CAP, a standardized approach of adding early empiric anti-influenza therapy during the influenza season to hospitalized patients with suspect CAP and LRTI will improve clinical outcomes of patients with influenza associated CAP and LRTI.

To test our hypothesis we plan a prospective, randomized, multicenter clinical trial of hospitalized patients with acute LRTI, including suspect CAP, during . If early anti-influenza medications were not included on the patients admission orders, patients will be randomized to standard care, including empiric antibacterial therapy as recommended by ATS/IDSA guidelines plus standard influenza diagnostics and treatment (Standard of care) versus early initiation of empiric antiinfluenza therapy plus standard care, e.g. empiric antibacterial (osel

Detailed Summary:

This will be both a prospective, randomized, unblinded clinical study of hospitalized patients with acute LRTI admitted in one of four institutions in Louisville, KY (rapid empiric treatment with oseltamivir study[RETOS]) and a prospective observation study to describe influenza LRTI (Flu LRTI study). All hospitalized patients with acute LRTI will be invited to participate in one of the arms of study. If the admitting clinician does not order oseltamivir or zanamivir at the time of hospital admission, the patient is eligible for randomization into Group A (standard clinical care, including empiric antibiotics and anti-influenza drugs at the clinician discretion) or Group B (oseltamivir administered to the patient within 24 hours of admission, ideally within 8-12 hours of admission, plus empiric antibiotics). If the admitting clinician orders oseltamivir or zanamivir the patient is not eligible for randomization but is eligible for enrollment into an observational study that will describe the clinical course and outcomes of patients with influenza LRTI (Group C).

The primary Aim for the influenza LRTI study (Group C) is to describe hospitalized patients with LRTI who were suspected to have influenza at the time of admission, including the proportion w PCR confirmation, and selected clinical outcomes and clinical failure.

Patients will be enrolled from one of four hospitals, the University of Louisville Hospital, Veterans Affairs Medical Center of Louisville, Norton Hospital of Louisville, and Jewish Hospital of Louisville. Eligible patients will be identified primarily in the Emergency Departments of all four hospitals and evaluated for inclusion/exclusion criteria after hospital admission orders are written. Patients will be enrolled only during the influenza season. For this study, the influenza season is defined as Decem
Sponsor: University of Louisville

Current Primary Outcome: Clinical Failure [ Time Frame: 7 days ]

Any of the following:

  1. Lack of clinical improvement within 7 days. Criteria for clinical improvement include no fever; white blood cell count decreases, or increases in the case of leukopenia, to more than 10% from the prior day; the evaluation of signs and symptoms of CAP to define when the patient is subjectively better, and the patient is able to tolerate food by mouth.
  2. Need for intensive care admission.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Cost-effectiveness [ Time Frame: 30 days ]
    We will measure (1) all costs associated with administering antibiotic use and anti-influenza use, (2) costs of hospital stay (measured as average cost per day), (3) length of stay in the hospital, (3) cost of all diagnostic tests performed, and (4) rate of clinical failure. Combined with the within-trial data an estimate of the incremental cost-effectiveness ratio according to a traditional decision analytic model will be calculated. Estimation of cost will adhere to current standards. Rate of clinical failure will be calculated from the within trial data
  • Long-term mortality [ Time Frame: 1 year ]
    Death within 1 year of enrollments
  • Short-term mortality [ Time Frame: 30 days ]
    Death within 30 days of enrollment
  • Re-hospitalization [ Time Frame: 30 days ]
    Re-hospitalization within 30 days after enrollment.


Original Secondary Outcome: Same as current

Information By: University of Louisville

Dates:
Date Received: November 23, 2010
Date Started: November 2010
Date Completion:
Last Updated: March 21, 2017
Last Verified: March 2017