Procalcitonin Antibiotic Consensus Trial (ProACT)

Study Overview
=================
Brief Summary
-----------------
The ProACT study is a 5 year, multicenter study that will test the effect of implementation of a novel procalcitonin guideline on antibiotic use and adverse outcomes in Emergency Department (ED) patients with Lower Respiratory Tract Infection (LRTI).

Detailed Description
-----------------
There is a need for improved decision-making for antibiotic prescription in acute suspected infection. Infections, particularly in the early stages, can have protean manifestations, often do not manifest with classic signs, and clinically overlap with non-infectious conditions. However, the imperative to quickly give antibiotics for bacterial infection has led to antibiotic overuse and resistance. Strategies that combine novel diagnostics with therapeutics have improved decision-making in oncology, cardiology, and other fields. These strategies aim to identify those patients most likely to be helped or harmed by the therapeutic intervention and allow more individualized care. This approach takes diagnostics to the next level, by demanding a test not only measure well, but also that clinical care be improved by tying the test to a treatment strategy. Procalcitonin, a novel biomarker of bacterial infection, may help physicians make more appropriate antibiotic decisions. Lower respiratory tract infection (LRTI) is an ideal trial population. LRTI accounts for a large proportion of antibiotic prescription, and exemplifies the imprecise clinical phenotype of infection.However, key questions of generalizability and safety preclude widespread application.

Official Title
-----------------
Procalcitonin Antibiotic Consensus Trial (ProACT)

Conditions
-----------------
Lower Respiratory Tract Infection (LRTI)

Intervention / Treatment
-----------------
* Other: Procalcitonin level
* Other: Results of procalcitonin (PCT) level to treating clinician
* Other: Provide procalcitonin guideline to treating clinician
* Other: Telephone Visit


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years old A primary clinical diagnosis in the ED of acute LRTI (< 28 days duration) Clinician willing to consider procalcitonin in antibiotic decision-making Exclusion Criteria: Systemic antibiotics before ED presentation (All prophylactic antibiotic regimens, OR received >1 dose within 72 hours prior to ED presentation) Current vasopressor use Mechanical ventilation (via endotracheal tube) Known severe immunosuppression Accompanying non-respiratory infections Known lung abscess or empyema Chronic dialysis Metastatic cancer Surgery in the past 7 days (excluding minor surgery such as skin biopsy) Incarcerated or homeless Enrolled in ProACT in the past 30 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Procalcitonin (PCT) group<br>Procalcitonin (PCT) level; Results of procalcitonin level to treating clinician; Provide procalcitonin guideline to treating clinician; Telephone Visit at Day 15 and Day 30 | Other: Procalcitonin level<br>* A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion.<br>* Other names: PCT level;Other: Results of procalcitonin (PCT) level to treating clinician<br>* In the ED, we will quickly (<1 hour goal) provide clinicians the procalcitonin result.<br>Other: Provide procalcitonin guideline to treating clinician<br>* Procalcitonin antibiotic guideline -- Procalcitonin level (ug/L) -- Bacterial etiology -- Recommendation < 0.1 -- Very unlikely -- Antibiotics strongly discouraged(1) 0.1 - 0.25 -- Unlikely -- Antibiotics discouraged(1) > 0.25 - 0.5 -- Likely -- Antibiotics recommended(2) > 0.5 -- Very likely -- Antibiotics strongly recommended(2) Initial antibiotics can be considered for critical illness, Legionella pneumophilia. Procalcitonin should be evaluated in context with all findings and the total clinical status; clinical judgment always necessary. For outpatients, antibiotic duration based on level (> 0.25-0.5 ug/L:3 days; > 0.5-1.0 ug/L:5 days; >1.0 ug/L:7 days). Physician follow-up is recommended.<br>Other: Telephone Visit<br>* We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30<br>|
| Active Comparator: Usual Care group<br>Telephone Visit at Day 15 and Day 30 | Other: Telephone Visit<br>* We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Antibiotic Exposure Days | Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30. | 30 days | 
| Number of Participants With Any Adverse Outcome | Primary Safety Outcome - Combined endpoint of adverse outcomes (death, endotracheal intubation, vasopressors, renal failure, lung abscess/empyema, pneumonia in non-CAP patient, and hospital readmissions) that could be attributable to withholding antibiotics in lower respiratory tract infection (LRTI). Number is based on the number of participants that experienced any adverse outcome. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibiotic Prescription in Emergency Department(ED) | Antibiotic prescription in the ED includes post-randomization receipt of antibiotics in ED and provision of an antibiotic prescription for patients at the time of discharge from the ED. | While in the ED or before ED discharge (majority patients < 1 day) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
procalcitonin (PCT), lower respiratory tract infection (LRTI), antibiotic exposure, antibiotic decision making, community acquired pneumonia (CAP), chronic obstructive pulmonary disease (COPD) exacerbation, acute asthma exacerbation, acute bronchitis, procalcitonin guideline