Clinical trial NCT04166110: Antibiotic Therapy In Respiratory Tract Infections
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Community-Acquired Pneumonia
Keywords: community-acquired pneumonia
antibiotic therapy duration strategy
non-inferiority trial
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-11-18
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cure rate at day 15
timeFrame: Day 15
Secondary outcomes:
measure: Cure rate at day 30
timeFrame: Day 30
measure: Duration of antibiotic treatment
timeFrame: Up to 14 days
measure: Frequency and severity of adverse events
timeFrame: through study completion, an average of 30 days
measure: Evolution of pneumonia symptoms
timeFrame: through study completion, an average of 30 days
Other outcomes:
Locations:
city: Garches
country: France
facility: Unité des Maladies Infectieuses, CHU Raymond Poincaré
state: Île-de-France
Study officials:
affiliation: Unité des Maladies Infectieuses, Hôpital Raymond Poincaré, Garches
name: Aurélien DINH, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service des maladies infectieuses, Hôpital Saint Louis, Paris
name: Anne-Claude CRÉMIEUX, MD, PhD
role: STUDY_DIRECTOR
References: