Tailoring Antibiotic Duration for Respiratory Tract Infections in Primary Care (STORM)

Tailoring Antibiotic Duration for Respiratory Tract Infections in Primary Care: a Pragmatic Randomized Controlled Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Tract Infection

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' 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'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.

• Study Type: Interventional
• Enrollment (Estimated): 474
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ramon Monfà, MSc; Phone Number: 0034685409860; Email: rmonfa@idiapjgol.org
• Study Contact Backup: Name: Ana García-Sangenís, MSc; Phone Number: 0034638687717; Email: agarcia@idiapjgol.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical resolution	Number of patients with disappearance of fever, disappearance or improvement in overall condition (all scores <2), such that no additional antimicrobial treatment is necessary.	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of antibiotic therapy	Number of patients discontinuing treatment in both groups and what day they discontinue recorded	Day 14
Doses taken	Number of doses of antibiotic taken	Day 14
Duration of severe symptoms	Number of days until the last day the patient scores 5 in any of the symptoms in the RTI diary symptom	Day 14
Duration of moderate symptoms	Number of days until the last day the patient scores 3 in any of the symptoms in the RTI symptom diary.	Day 14
Total resolution of symptoms	Number of days until the last day the patient scores 0 in any of the symptoms in the RTI symptom diary.	Day 14
Re-attendance rate	Number of re-attendances to any doctor for new or worsening symptoms regarding the RTI regarding the infection	Day 28
Complication rate	Number of complications related to the infection, such as visits to emergency departments and/or hospital admissions regarding the RTI	Day 28
Absenteeism	Number of days of work absenteeism due to the infectious disease	Day 14
Adverse events	Drug-associated adverse events related to the antibiotic and antibiotics changed	Day 14
Use of other medication	Number of participants using antibiotics others than the study medication and other symptomatic therapies within the first two weeks	Day 14
Health quality of life	Variation of the score of the health-related quality of life on days 14 and 28, compared to baseline, measured using the EuroQol instrument, including visual analogical scale, ranging from 0 (worst health condition) to 100 (best health condition)	Day 28

Collaborators and Investigators

• Sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: August 28, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): September 3, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Primary Health Care; Personalized Medicine; Duration; Patient-Centered Care; Drug Resistance, Microbial; Antibacterial Agents Antimicrobial Resistance; Drugs, Customized
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: IJG-STORM-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sharing of the individual participating data, study protocol and statistical analysis plan.
• IPD Sharing Time Frame: 2025 until 2027
• IPD Sharing Access Criteria: All the investigators who want to have this information shared under request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No