Customized Antibiotic Treatment Duration Among Hospitalized Patients With Moderately Severe Community-Acquired Pneumonia

NCT05903352 | Recruiting Phase 3 DMC

• 2 other identifiers: APHP2208142023-504208-27-00
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate if the efficacy of an experimental strategy on antibiotic treatment duration based on stopping treatment when stability criteria are reached after at least 48 h of treatment, is non-inferior to the efficacy of standard antibiotic duration in CAP patients treated in the hospital setting. As the secondary objectives, the study aims

• To study if the efficacy of our experimental strategy on antibiotic treatment duration compared to standard of care in CAP patients treated in the hospital setting is non-inferior in terms of:
• Persistence of cure at Day 30 of antibiotic treatment
• All-cause mortality rate on Day 30 of antibiotic treatment
• Patients evolution of pneumonia symptoms and quality of life via 2 scores (CAP score, CAP Sym) at Day 0 of treatment (retrospectively), at stability (Day S), at Day 7 , at Day 15, and at Day 30 of antibiotic treatment.
• To compare between the 2 study arms at Day 30 of antibiotic treatment:
• The duration of antibiotic treatment;
• The length of hospital stay;
• The frequency and severity of adverse events during the 30 days after the start of treatment.
• To explore the impact of reduced antibiotic treatment duration for CAP on the oropharyngeal resistome.

Conditions

Community-Acquired Pneumonia

Keywords

Community-Acquired Pneumonia; Antibiotic treatment duration; Antibiotic resistance; Infectious diseases

Outcome Measures

Primary Outcomes (1)

• Rate of cure at Day 15 after treatment initiation

  Cure at Day 15 will be defined by the association of: * Persistence of stability criteria (body temperature ≤ 37.8°C; heart rate ≤ 100/min; systolic blood pressure \> 90mmHg; oxygen saturation ≥ 92%; respiratory rate \< 24/min; normal mental status); * No additional antibiotic treatment, targeting CAP, taken after the end of initial antibiotic treatment. Patients who died, or are not cured as defined above, will be classified as failure at Day 15.

  Day 15

Secondary Outcomes (9)

• Rate of cure at Day 30

  Day 30

• Mortality on Day 30

  Day 30

• Patients' evolution of pneumonia symptoms

  Day-0, Day S, Day 7, at Day 15, and at Day 30

• Patients' evolution of pneumonia symptoms

  Day 15 and Day 30

• Duration of antibiotic treatment targeting CAP

  Day 30

Study Arms (2)

Antibiotic treatment

PLACEBO COMPARATOR

Antibiotic treatment duration left to the physician's judgment (usual practice: total treatment duration between 5 to 10 days according to French guidelines; more than 7 days of treatment should be justified).

Drug: Continue the antimicrobial treatment

Interruption of treatment

EXPERIMENTAL

Interruption of treatment based on the patient reaching all of the following stability criteria (body temperature ≤ 37.8°C; heart rate ≤ 100/min; systolic blood pressure \> 90mmHg; oxygen saturation ≥ 92%; respiratory rate \< 24/min; normal mental status (27)), with a treatment duration no shorter than 48 h.

Other: Stop antibiotic

Interventions

Stop antibiotic OTHER

Stop the antibiotic treatment on day S (stability criteria reached for 24 h or within 48 hours after the start of antibiotic treatment).

Interruption of treatment

Continue the antimicrobial treatment DRUG

Continue the antimicrobial treatment for a duration predetermined by the investigator (usual practice, at least 5 days of treatment in total).

Antibiotic treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patient (≥18 years old)
• Admitted to hospital for suspected CAP defined by the presence of at least 2 of the following diagnostic clinical criteria:
• Fever (temperature \> 38°C) or hypothermia (\< 36°C)
• Dyspnea
• Cough
• Production of purulent sputum
• Crackles
• Radiological evidence of a new infiltrate (chest X-ray or CT scan)
• Negative viral respiratory testing
• Treated for a minimum of 48 hours with antibiotics (excluding azithromycin due to its prolonged half-life)Presenting with an early clinical response within the last 24 hours (up to 7 days after the start of antibiotic treatment, if planned treatment duration \> 7 days), defined by the presence of all the following criteria:apyrexia (T°C ≤ 37.8)heart rate \< 100/minrespiratory rate \< 24/min, according to the patient's usual mode of oxygenation,arterial oxygen saturation ≥ 92%, according to the patient's usual mode of oxygenation,Patient currently under antibiotic treatment for his suspected CAP (i.e. the last dose of ATB has been administered to the patient less than 24 hours ago)
• Patient presenting a clinical response within the last 24 hours defined by the presence of all the following criteria:
• apyrexia (T°C ≤ 37.8)
• heart rate \< 100/min
• respiratory rate \< 24/min, according to the patient's usual mode of oxygenation,
• arterial oxygen saturation ≥ 92%, according to the patient's usual mode of oxygenation,

You may not qualify if:

• Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency)
• Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, transplant, myeloma, lymphoma, known HIV and CD4\<200/mm3)
• Suspected or confirmed legionellosis
• Any other infection necessitating concomitant antibiotic treatment
• Confirmed or suspected aspiration pneumonia or healthcare-associated pneumonia
• Treatment of suspected CAP with azithromycin (due to its prolonged half-life)
• 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, uncontrolled arterial hypertension, atherosclerosis (only for patients treated with fluoroquinolones antibiotics)
• Pregnant or breastfeeding woman
• Life expectancy \< 1 month
• Patient under legal guardianship (French "tutelle" or "curatelle")
• Patient without fixed address
• Patient enrolled in another interventional clinical trial on CAP treatment

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Infectious diseases department, Raymond-Poincaré Hospital - APHP

Garches, 92380, France

RECRUITING

Related Publications (1)

• Dinh A, Ropers J, Duran C, Davido B, Deconinck L, Matt M, Senard O, Lagrange A, Makhloufi S, Mellon G, de Lastours V, Bouchand F, Mathieu E, Kahn JE, Rouveix E, Grenet J, Dumoulin J, Chinet T, Pepin M, Delcey V, Diamantis S, Benhamou D, Vitrat V, Dombret MC, Renaud B, Perronne C, Claessens YE, Labarere J, Bedos JP, Aegerter P, Cremieux AC; Pneumonia Short Treatment (PTC) Study Group. Discontinuing beta-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial. Lancet. 2021 Mar 27;397(10280):1195-1203. doi: 10.1016/S0140-6736(21)00313-5.

  PMID: 33773631 BACKGROUND

MeSH Terms

Conditions

Community-Acquired Pneumonia; Communicable Diseases

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Aurélien Dihn, MD, PhD

  Infectious diseases department, Raymond-Poincaré Hospital - APHP

  PRINCIPAL INVESTIGATOR

• Jacques Ropers, PharmD

  Clinical Research Unit Pitié Salpêtrière - Charles Foix, CHU La Pitié-Salpêtrière - APHP

  STUDY DIRECTOR

Central Study Contacts

Aurélien Dinh, MD, PhD

CONTACT

+ 33 (0)1 47 10 44 32; aurelien.dinh@aphp.fr

Jacques Ropers, PharmD

CONTACT

+ 33 01 42 16 03 48; jacques.ropers@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All eligible patients with confirmed CAP and willing to participate will be included and randomly assigned (1:1 ratio) by the investigator, to either continue the antimicrobial treatment for a duration predetermined by the investigator (usual practice, at least 3 days of treatment in total), or to stop the antibiotic treatment.

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: June 15, 2023
• Study Start: February 5, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

FR (1)