Viral Testing and Biomarkers to Reduce Antibiotic Use for Respiratory Infections

Study Overview
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Brief Summary
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This trial is a pilot study to determine the feasibility of a randomized clinical trial comparing a treatment algorithm consisting of a limited number of clinical parameters, rapid molecular viral diagnostics, and serum procalcitonin testing to standard of care for directing antibiotic use in patients with non-pneumonic lower respiratory tract infection. The reduction in antibiotic use in those subjects randomized to the treatment algorithm compared to those randomized to standard care will be determined.

Detailed Description
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This is trial is a pilot study to determine the feasibility of a randomized clinical trial comparing a treatment algorithm consisting of a limited number of clinical parameters, rapid molecular viral diagnostics, and serum procalcitonin testing to standard of care for directing antibiotic use in patients with non-pneumonic lower respiratory tract infection. The reduction in antibiotic use in those subjects randomized to the treatment algorithm compared to those randomized to standard care will be determined. In addition, the added benefit of viral diagnosis to that of serum procalcitonin alone in reducing antibiotics will be determined. Lastly, antibiotic related complications and clinical outcomes to determine the safety of this approach at 30 days and 3 months in the standard care and intervention group will be evaluated. Analysis of the composite adverse event outcome (death, intensive care unit transfer, disease specific complications and recurrent respiratory tract infection requiring hospitalization) will serve as the principle safety analysis for the study. In addition, each adverse outcome will be examined individually as well as lesser adverse outcomes including antibiotic prescriptions, time to return to baseline health, patient reported outcomes and functional status at 30 days and 3 months. Physicians will be queried to determine factors which drive antibiotic prescriptions and potential barriers to implementing antibiotic reduction algorithms. These data will be used to design a phase III clinical trial with the intent to demonstrate that physicians in the US will respond appropriately to this information and that antibiotic use can be significantly and safely curtailed.

Official Title
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Viral Testing and Biomarkers to Reduce Antibiotic Use for Respiratory Infections

Conditions
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Respiratory Infections

Intervention / Treatment
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* Other: Release of test results


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized with symptoms of a respiratory infection Age > 21 years Systolic Blood Pressure > 90mm Hg Patient or health care designee can provide written informed consent Exclusion Criteria: Intensive Care Requirement Antibiotics received prior to admission More than 24 hours of antibiotics received prior to enrollment Active chemotherapy or pulmonary radiation therapy Immunosuppressive conditions Conditions know to increase PCT values Definite infiltrate on CXR •% of band forms in peripheral blood > 15

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of care<br>Standard of care for respiratory infections | |
| Experimental: Release of test results<br>Health care providers will receive viral PCR and PCT test results along with an algorithm recommending antibiotic treatment based on PCT level. | Other: Release of test results<br>* Subjects will be randomized to have viral testing and serum PCT results released or no additional testing performed other than that ordered as standard of care<br>* Other names: Serum Procalcitonin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibiotic days | The primary patient-level outcome is the number of days on antibiotics after randomization. The primary null hypothesis is that the distribution of the number of days on antibiotics is identical for the standard-of-care versus intervention arm, where the latter includes those patients for whom the PCT-intervention recommendation was overruled by the care team. | Total antibiotic days within 30 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite adverse events at 30 days and 3 months | The secondary analyses will compare the following outcome variables between the intervention and the standard care group. Outcome variables will include total antibiotic related complications, length of hospitalization, a composite of 30 day and 3 month adverse events (death, ICU transfer, disease specific complications [development of pneumonia, lung abscess, empyema or ARDS] and recurrent LRTI requiring hospitalization). | 30 days and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory, Viruses, Bacterial, Antibiotics, Procalcitonin