The Procalcitonin Guided Antibiotics in Respiratory Infections in General Practice (PARI)

Antimicrobial resistance rates have reached alarming levels and the Worlds Health Organisation (WHO) states it constitutes a serious public health concern by threatening one of the most effective and mortality lowering interventions in modern medicine. Part of the solution to this problem includes minimizing overuse of antibiotics. But clinical signs alone are often not reliable to guide antibiotic treatment decisions and additional tests may be warranted to assist the doctor. Such tests include point-of-care biomarkers of infection like C-reactive protein (CRP) and procalcitonin (PCT). Targeting antibiotic use to the few patients with a high probability of benefit and withholding in the many with non-serious respiratory infection is a promising strategy and readily implemented in clinical practice.

The Procalcitonin guided Antibiotics in Respiratory Infections (PARI) study will assess the effect of a novel point-of-care PCT guided antibiotic stewardship in acute respiratory tract infections in general practice.

The overall aim of the PARI study is to reduce antibiotic use in patients with acute respiratory tract infections by targeting antibiotic treatment only to patients with a suspected bacterial etiology and thus likely to benefit from antibiotic therapy.

The main research questions are:

Does the addition of a point-of-care Procalcitonin test to standard care reduce antibiotic use in primary care? Is the intervention safe for the patients? The PARI study is a pragmatic two-arm (intervention and control (standard care) open randomized non-inferiority trial (up to 1 day difference in recovery) in general practice.

Study Overview

• Status: Withdrawn
• Conditions: Acute Respiratory Tract Infection
• Intervention / Treatment: Diagnostic test: Procalcitonin

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 1620
    • Lægerne Finne, Riise og Aabenhus
  • Copenhagen, Denmark, 2300
    • Amagercentrets læger
  • Copenhagen, Denmark, 2610
    • Mit Lægehus
  • Haslev, Denmark, 4690
    • Haslev Lægecenter
  • Næstved, Denmark, 4700
    • Næstved Lægecenter
  • Rønnede, Denmark, 4683
    • Rønnede lægehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age above 18 years
• Able to read and understand patient information about the PARI trial and willing to give written informed consent prior to enrollment
• Acute cough e.g. less than 2 weeks probable acute upper or lower respiratory tract infection (pharyngitis, tonsillitis, otitis media, sinusitis, exacerbations of asthma or Chronic Obstructive Pulmonary Disease (COPD), bronchitis or pneumonia)
• C-Reactive Protein >20 mg/m

Exclusion Criteria:

• Symptoms present for more than 2 weeks
• Verified immunodeficiency or presently neutropenic (neutrophile granulocytes ≤0,5 x 109/L within the last 7 days)
• Severe liver failure
• Severe kidney failure including dialysis
• Sore throat and positive test for Group A streptococcus
• Prior antibiotic exposure last 14 days up to inclusion
• Need for acute admission to hospital
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Procalcitonin in addition to usual care; Procalcitonin values will be disclosed to the attending physician and assist in antibiotic guidance in addition to usual care	Diagnostic test: Procalcitonin; In addition to usual care diagnostic and handling of acute respiratory tract infections in general practice to attending physician in the intervention arm has access to antibiotic stewardship by a procalcitonin point-of-care test. The following criteria for initiating og withholding antibiotics will be used.; Antibiotics treatment is recommended with Procalcitonin levels above 0.25 ng/ml; Antibiotic treatment is discouraged if Procalcitonin levels are below 0.25 ng/ml
No Intervention: Usual care; Usual best standard care. No procalcitonin values disclosed to attending physician .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of illness and symptoms from acute respiratory tract infections.	The patient reported primary outcome will be assessed as number of days to a patient's daily activities (work or recreation) are no longer restricted by symptoms from a respiratory tract infection.The non-inferiority margin between the intervention and control group is set at a one day difference. The recovery measure will be the specific day indicated by the participants using the validated Acute Respiratory Tract Infections Questionaire (ARTIQ).	up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibiotic treatments	Number of participants in each trial arm exposed to antibiotic treatment at index consultation (day 1) and within 30 days	1, 14 and 30 days
Side effects from antibiotic treatment	Number of participants in each trial arm with side effects from antibiotic treatment	14 days
re-consultations	Number of participants in each trial arm with re-consultations	30 days
Severe adverse effects	Number of participants in each trial arm admitted to hospitalization (including diagnosis and mortality)	30 days
Biomarker levels	Characterisation of biomarker (C-Reactive Protein and Procalcionin) levels at index consultation.	day 1

Collaborators and Investigators

• Sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Collaborators: Research Unit Of General Practice, Copenhagen; Department of Public Health, Denmark
• Investigators: Study Chair: Lars Bjerrum, PhD, Department of Public Health, Copenhagen University, Denmark

Publications and helpful links

General Publications

• Filipsen N, Bro H, Bjerrum L, Jensen JS, Aabenhus R. The Procalcitonin-guided Antibiotics in Respiratory Infections (PARI) project in general practice - a study protocol. BMC Prim Care. 2022 Mar 12;23(1):43. doi: 10.1186/s12875-022-01646-6.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2020
• Primary Completion (Actual): August 1, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 30, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: primary care; Procalcitonin; Antibiotic use; general practice; acute respiratory tract infection
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: 18057336

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: work in progress
• IPD Sharing Time Frame: Upon publication of study results
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No