The Procalcitonin Guided Antibiotics in Respiratory Infections in General Practice

Overview

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 Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Diagnostic
  • Masking: Single (Participant)
• Study Primary Completion Date: August 1, 2022

Interventions

• 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

Arms, Groups and Cohorts

• 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
• No Intervention: Usual care
  • Usual best standard care. No procalcitonin values disclosed to attending physician .

Clinical Trial Outcome Measures

Primary Measures

• Duration of illness and symptoms from acute respiratory tract infections.
  • Time Frame: up to 14 days
  • 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).

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Collaborator
  • Research Unit Of General Practice, Copenhagen
• Provider of Information About this Clinical Study
  • Principal Investigator: Rune Munck Aabenhus, MD. Specialist in General Practice, PhD, Assistent Professor – Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Overall Official(s)
  • Lars Bjerrum, PhD, Study Chair, Department of Public Health, Copenhagen University, Denmark