Antibiotic Therapy In Respiratory Tract Infections

Community-Acquired Pneumonia Clinical Trial

— AIR  

Official title:

A Controlled Randomized, Open Label, Multicenter, Non-inferiority Trial Evaluating an Individualized Antibiotic Duration Treatment Based on Patient Clinical Response, Evaluated Through Connected Devices, for Community Acquired Pneumonia in the Community Setting

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04166110
• Other study ID #: P160929J
• Secondary ID: 2019-001873-10
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2023
• Est. completion date: December 2025

Study information

• Verified date: May 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Aurélien DINH, MD
• Phone: + 33 1 47 10 44 32
• Email: aurelien.dinh[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary aim: to demonstrate that stopping antibiotic treatment in patients diagnosed with acute community acquired pneumonia (CAP) based on clinical response has a non-inferior efficacy 15 days after start of treatment, compared to a conventional predetermined duration left to the physician's judgement, in adults treated in the community setting. Secondary aims: To compare the 2 study arms on: 1. Clinical success at late follow up (Day 30), 2. Duration of antibiotic treatment, 3. Frequency and severity of adverse events, 4. Patient's pneumonia symptoms and quality of life.

Description:

Recent studies have suggested that CAP can be successfully treated by short-course antibiotic regimen when clinical improvement is rapidly obtained. Even if clinical response is obtained in 3 days in the majority of cases, it can widely vary among patients, suggesting that "one duration does not fit all". An individualized duration of therapy depending on the patient's response could help to ensure bacterial eradication while avoiding unnecessary antibiotic exposure and thus reduce antibiotic resistance. At present, this strategy has never been tested. This is a pragmatic open label non-inferiority randomized multicenter trial with two parallel arms comparing antibiotic treatment duration left to the physician's judgement (usually 7 to 14 days), versus interruption of treatment based on the patient's clinical response defined by reaching stability criteria (body temperature ≤ 37.8°C; heart rate ≤ 100/min; systolic blood pressure ≥ 90mmHg, oxygen saturation ≥ 90%) for 24h, after a minimum of 2 days treatment. Recruitment and follow-up: Outpatients consulting in a private multiprofessional health center, diagnosed as having CAP and in need for antibiotics will be assessed for eligibility. Following information and signing consent, eligible patients will be included in the study. They will receive the prescription (antibiotic type and duration determined by the physician, preferably chosen according to the French guidelines) and a collection of connected devices to monitor their vital signs 2 times a day (morning and evening). Preselected patients will be randomized as soon as they meet the two following criteria: i) they have presented the stability criteria for 24h (3 consecutive vital signs recordings); ii) they have started the antibiotic treatment at least 72 hours before, with a ≥ 80% compliance, and with at least 1 intake in the last 24 hours. Each patient will then receive a telephone call from the coordinating team (or a permanent medical platform at nights, during weekends or public holidays) in order to proceed to the randomization and ensure that everything is well understood by the patient as well as the security and compliance with the strategy. A follow-up visit with the investigator will be performed at day 15 after the start of antibiotic treatment. The final evaluation will be performed 30 days following the start of antibiotic treatment by a telephone call from the coordinating team. Number of subjects necessary: 310 patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 310
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient aged 18 years or more
• Has given written informed consent
• Affiliated to Health insurance
• Is able to take oral treatment
• Presenting with suspected CAP defined by the presence of at least 2 of the following

diagnostic clinical criteria:

• Fever (temperature > 38°C)
• Dyspnea
• Cough
• Production of purulent sputum
• Crackles
• Radiological evidence of a new infiltrate (on chest X-ray or CT scan)
• In need for antibiotic treatment targeting respiratory tract, according to the physician in charge
• No other site of infection besides respiratory Exclusion Criteria: All subjects meeting any of the following exclusion criteria at baseline will be excluded

from study participation:

• Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency)
• Hospitalization following consultation
• Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, immunosuppressive treatments or corticosteroids (prednisolone equivalent) > 10 mg/day, transplant, myeloma, lymphoma, known HIV and CD4<400/mm3, sickle-cell disease, Child-Pugh class C cirrhosis)
• Suspected or confirmed legionellosis
• Atrial fibrillation / constitutive tachycardia
• Baseline oxygen saturation < 90% or home oxygen therapy
• More than 24 hours of antibiotics prior to consultation
• Any other infection necessitating concomitant antibiotic treatment
• Contraindications to the study antibiotics
• Concomitant steroid treatment only for patients treated with fluoroquinolones antibiotics
• Pre-existing aortic aneurysm or dissection, family history of aortic aneurysm or dissection, Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arthritis, arterial hypertension, atherosclerosis only for patients treated with fluoroquinolones antibiotics
• Pregnancy
• Breastfeeding
• Life expectancy < 1 month
• Patient under legal guardianship or without healthcare coverage
• Homeless patient
• Patient enrolled in another interventional clinical trial.

Related Conditions & MeSH terms

• Community-Acquired Pneumonia
• Pneumonia

Intervention

Drug:
• Predetermined treatment duration
Antibiotic treatment duration left to the physician's judgement (following national guidelines, 7 to 14 days)
• Variable treatment duration
Treatment duration vary according to stability criteria reaching time Patients will self-monitor 2 times a day (in the morning and in the evening) using a set of connected devices, to monitor their vital signs before any treatment intake. After at least 3 days of treatment and stability criteria obtained for the last 24 hours (i.e. 3 vital signs recording), patients will stop the antibiotic treatment.

Locations

Country	Name	City	State
France	Unité des Maladies Infectieuses, CHU Raymond Poincaré	Garches	Île-de-France

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cure rate at day 15	Cure rate is the number of patients who are cured, as defined by the association of 3 criteria : stability: body temperature = 37.8°C; heart rate = 100/min; systolic blood pressure > 90mmHg and oxygen saturation = 90%.; absence of: incidence of coughing, sputum production, shortness of breath and crackles.; absence of additional antibiotic taken after the end of initial antibiotic treatment.; Clinical evaluation at Day 14 or Day 16 is allowed to take into account.	Day 15
Secondary	Cure rate at day 30	Cure rate is the number of patients who are cured, as defined by the association of 2 criteria: absence of: incidence of coughing, sputum production, shortness of breath and crackles.; absence of additional antibiotic taken after the end of initial antibiotic treatment.	Day 30
Secondary	Duration of antibiotic treatment		Up to 14 days
Secondary	Frequency and severity of adverse events		through study completion, an average of 30 days
Secondary	Evolution of pneumonia symptoms	Patients' evolution of pneumonia symptoms and quality of life between the 2 study arms (CAP Score / CAP Sym)	through study completion, an average of 30 days