Viral Testing and Biomarkers to Reduce Antibiotic Use for Respiratory Infections

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Infections
• Intervention / Treatment: Other: Release of test results

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14621
      • Rochester General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care; Standard of care for respiratory infections
Experimental: Release of test results; 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; 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; Other Names: Viral PCR; Serum Procalcitonin

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physician attitudes regarding antibiotic prescription	Physicians will be queried 24 hours after release of intervention results of viral testing and PCT values to understand factors associated with continuing or stopping antibiotics	24 hours after release of intervention test results

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: Rochester General Hospital
• Investigators: Principal Investigator: Ann R Falsey, MD, University of Rochester

Publications and helpful links

General Publications

• Branche AR, Walsh EE, Vargas R, Hulbert B, Formica MA, Baran A, Peterson DR, Falsey AR. Serum Procalcitonin Measurement and Viral Testing to Guide Antibiotic Use for Respiratory Infections in Hospitalized Adults: A Randomized Controlled Trial. J Infect Dis. 2015 Dec 1;212(11):1692-700. doi: 10.1093/infdis/jiv252. Epub 2015 Apr 24.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: June 27, 2013
• First Submitted That Met QC Criteria: July 24, 2013
• First Posted (Estimate): July 25, 2013

Study Record Updates

• Last Update Posted (Estimate): July 2, 2014
• Last Update Submitted That Met QC Criteria: June 30, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Antibiotics; Procalcitonin; Respiratory; Viruses; Bacterial
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: ABX RED-001; RGH KIDD-001 (Other Identifier: Rochester General Hospital KIDD Fund)