Clinical trial NCT06581367: Tailoring Antibiotic Duration for Respiratory Tract Infections in Primary Care
Official title: Tailoring Antibiotic Duration for Respiratory Tract Infections in Primary Care: a Pragmatic Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Acute Respiratory Tract Infection
Keywords: Antibacterial Agents Antimicrobial Resistance
Duration
Primary Health Care
Personalized Medicine
Drugs, Customized
Drug Resistance, Microbial
Patient-Centered Care
Lead sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
Sponsor class: OTHER
First posted: 2024-09-03
Enrollment: 474
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients with acute RTIs will be randomized to either usual care (full-course antibiotic therapy based on current guidelines), or a tailored approach (patients will be advised to visit the center as soon as they feel better and are afebrile for a clinical assessment and C-reactive protein rapid testing after completing two full days of antibiotic).
Primary purpose: TREATMENT

Brief summary: The rise of drug-resistant organisms and the need to minimize side effects calls for a new approach to antibiotic therapy duration. This study explores tailoring the length of antibiotic treatment to patient recovery, focusing on whether adjusting therapy based on when the patient feels better is as effective as completing the prescribed course for acute respiratory tract infections (RTIs). The investigators will enroll 474 outpatients aged 18-75 with acute RTIs across 25 Spanish healthcare centers. Patients will be randomized into two groups: one following standard full-course antibiotic therapy, and another receiving a tailored approach, where treatment may be shortened based on clinical assessments. The primary outcome is clinical efficacy at day 14. Secondary outcomes include antibiotic duration, complications, and quality of life.

Detailed description: Background. Combating the rise of drug-resistant organisms and minimizing the side effects demand a shift in how we approach antibiotic therapy duration. A study focused on tailoring antibiotic length of therapy to patients\&#39; needs as soon as they feel better, is a promising strategy. The investigators aim to assess whether adjusting the duration of antibiotic therapy according to individual patient needs, shortening it to the time when the patient feels better, proves as effective as completing the antibiotic course in acute respiratory tract infections (RTIs).

Methods. The investigators plan to enroll a minimum of 474 outpatients ranging from 18 to 75 years of age with clinical features of acute RTIs across 25 Spanish primary healthcare centers. Patients diagnosed with acute lower RTIs or acute rhinosinusitis, deemed by clinicians to require a beta-lactam course, will be randomized to either usual care, involving a full-course antibiotic therapy based on current guidelines, or a tailored approach. In the intervention group, patients will be advised to visit the center as soon as they feel better and are afebrile for a clinical assessment and C-reactive protein rapid testing after completing two full days of antibiotic. Treatment will be discontinued if these clinical results are normal. The primary outcome will be overall clinical efficacy at day 14, while secondary outcomes include duration, doses of antibiotic taken, complications and reattendance within the first month, drug-related adverse events, antibiotic given, other therapies, days of severe and moderate symptoms, days of symptoms, absenteeism and health-related quality of life. All participants will be given a symptom diary, recording their symptoms each evening. Additionally, a cost-effectiveness study and qualitative studies involving clinicians and patients aimed at exploring the strategy\&#39;s pros, cons, uptake, and satisfaction levels will be carried out.

Discussion. The investigators will examine whether adults who present with symptoms of acute lower RTI or rhinosinusitis in general practice, who are treated with antibiotic courses until they feel better are as effective as longer standard courses. It is highly important that a possible reduction in the antibiotic course as soon as the patient feels better does not compromise patients' recovery or clinical course, which we will assess closely. This comprehensive approach aims to shed light on the practicality and impact of tailoring antibiotic duration in RTIs.

Eligibility criteria: Inclusion Criteria:

* Either adults with a) acute cough (new cough or worsening of a previous cough) as the predominant symptom which the clinician believes to be a bacterial acute lower RTI, such as community-acquired pneumonia, acute bronchitis or acute chronic obstructive pulmonary disease (COPD) exacerbations, or b) an acute bacterial rhinosinusitis
* Doctors deem beta-lactam therapy (given every eight hours for a minimum of seven days) is necessary

Exclusion Criteria:

* RTIs different from a lower RTI or acute rhinosinusitis
* Patients with suspected septicemia (quick Quick Sequential Organ Failure Assessment: respiratory rate ≥22 breaths/minute, systolic blood pressure \<100 mm Hg or altered mental status with a Glasgow score \< 5) ≥2
* Patients with pneumonia and \[Confusion, respiratory rate ≥30 breaths/minute, blood pressure \< 90/60 mm Hg, or age \>65 yr.\] ≥1
* Patients with very severe COPD (Forced Expiratory Volume in One Second \<30%)
* Patients with COPD who have taken four or more antibiotic courses in the previous year, presence of significant bronchiectasis, and/or isolation of Pseudomonas in a previous sputum culture
* Patients with reported allergy to beta-lactams
* Patients who have taken an antibiotic in the previous two weeks
* Patients who have been hospitalized in the last two weeks
* A working diagnosis of a non-infective disorder, such as heart failure, pulmonary embolus, esophageal reflux
* Immunocompromised patients, such as HIV infection, patients taking immunosuppressive treatment, antineoplastic therapy, or systemic corticosteroids
* Currently participating in another clinical trial
* Previously participated in the STORM study
* Active neoplasia
* Terminal illness
* Institutionalized patient
* Inability/unable to understand and/or take part in the clinical trial

Primary outcomes:
measure: Clinical resolution
timeFrame: Day 14
Secondary outcomes:
measure: Duration of antibiotic therapy
timeFrame: Day 14
measure: Doses taken
timeFrame: Day 14
measure: Duration of severe symptoms
timeFrame: Day 14
measure: Duration of moderate symptoms
timeFrame: Day 14
measure: Total resolution of symptoms
timeFrame: Day 14
measure: Re-attendance rate
timeFrame: Day 28
measure: Complication rate
timeFrame: Day 28
measure: Absenteeism
timeFrame: Day 14
measure: Adverse events
timeFrame: Day 14
measure: Use of other medication
timeFrame: Day 14
measure: Health quality of life
timeFrame: Day 28
Other outcomes:
Locations:
Study officials:
affiliation: University Institute in Primary Care Research Jordi Gol, Barcelona
name: Rosa Morros, PhD
role: STUDY_CHAIR
References:
citation: Llor C, Frimodt-Moller N, Miravitlles M, Kahlmeter G, Bjerrum L. Optimising antibiotic exposure by customising the duration of treatment for respiratory tract infections based on patient needs in primary care. EClinicalMedicine. 2024 Jul 3;74:102723. doi: 10.1016/j.eclinm.2024.102723. eCollection 2024 Aug.