Rapid Empiric Treatment With Oseltamivir Study (RETOS)
Condition: Influenza; Pneumonia
MeSH terms: Influenza, Human; Pneumonia
Intervention: oseltamivir
Intervention description: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability
Intervention MeSH terms: Oseltamivir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pneumonia, bacterial; pneumonia, viral; respiratory tract infections; oseltamivir, therapeutic use

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 (oseltamivir group). The primary study outcome will be development of clinical
      failure and selected clinical outcomes during the 30 days after enrollment. Other clinical
      outcomes that will be compared between study groups include time to clinical stability,
      duration of hospitalization, development of cardiovascular events, re-hospitalization,
      short-term mortality (30 days), and long-term mortality (1 year). The secondary study outcome
      will be the cost-effectiveness of the intervention.
    

Eligibility criteria:

        Inclusion Criteria:

        For oseltamivir and standard of care groups:

          -  18 years of age or older

          -  No oseltamivir or zanamivir ordered in hospital admission orders

          -  Meets criteria for acute LRTI

          -  Signed informed consent.

        Exclusion Criteria:

        For oseltamivir and standard of care groups:

          -  Oseltamivir or zanamivir ordered in hospital admission orders

          -  Patients hospitalized for the LRTI for more than 24 hours before enrollment into the
             trial.

          -  Patients with mental conditions who are unlikely to comply with the study protocol and
             who cannot give informed consent and have no guardian or proxy.

          -  Patients who have had severe allergic reactions such as anaphylaxis or serious skin
             reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, or erythema
             multiforme to any component of oseltamivir (TAMIFLU).

          -  Prisoners