Clinical trial NCT06229288: Amoxicillin Alone Versus Amoxicillin/Clavulanate for Community-acquired Pneumonia in Patients Aged 65 Years or Older, and Hospitalized in a Non-intensive Care Unit Ward
Official title: Amoxicillin Alone Versus Amoxicillin/Clavulanate for Community-acquired Pneumonia in Patients Aged 65 Years or Older, and Hospitalized in a Non-intensive Care Unit Ward: a Non-inferiority Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Community-acquired Pneumonia
Keywords: Community-acquired pneumonia
Amoxicillin
Amoxicillin/clavulanate
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2024-01-29
Enrollment: 326
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Drug study, multi-centre, Phase 3, Controlled , Randomized, Open, Prospective
Primary purpose: TREATMENT

Brief summary: Reduce inappropriate antibiotic use is a priority of public health agencies. Community-acquired pneumonia (CAP) is one of the most important indications for antibiotic prescriptions.

In the majority of the studies of CAP, there is a large proportion of cases with no pathogen identified. Thus, the choice of the empirical antibiotic depends on the most likely pathogen, individual risk factors, comorbidities, and allergies.

Patients aged 65 years or older are often treated with amoxicillin/clavulanate or with another broad-spectrum antibiotic (third-generation cephalosporins, antipneumococcal fluoroquinolone). However, broad-spectrum antibiotic prescription in CAP is debated and concerns exist about side-effects and selective pressure for resistance. Due to lack of head-to-head antibiotic comparisons, a recent Cochrane review concluded that current evidence from Randomized Clinical Trials (RCTs) is insufficient to make evidence-based recommendations for the choice for antibiotic to be used, highlighting an important evidence gap.

Detailed description: Thus, the goal of the proposed trial is to compare clinical efficacy and safety of two CAP antimicrobial treatments, amoxicillin and amoxicillin/clavulanate, in patients aged 65 years or older and hospitalized in a non-intensive care unit (ICU) ward. The CAPTAIN study will be a multi-center, randomized, open, non-inferiority trial comparing clinical efficacy at Day 30 among patients ≥65 years of age, and hospitalized in a non-ICU ward, treated with narrow-spectrum (amoxicillin) versus broad-spectrum (amoxicillin/clavulanate) antimicrobial therapy for CAP. This will be a pivotal clinical trial that will provide evidence to inform CAP treatment guidelines.

Eligibility criteria: Inclusion Criteria:

1. Patient aged 65 years or older with or without comorbidities defined by chronic diseases in immunocompetent patients,
2. Patient admitted to the hospital for a CAP defined by at least two clinical signs of pneumonia (cough, sputum production, dyspnea, tachypnea, or pleuritic pain, abnormal lung auscultatory sounds, fever (temperature \> 38°C) or hypothermia (\<36°C)), and had radiological evidence of a new infiltrate confirming pneumonia
3. Patient understanding oral and written French
4. Written informed consent obtained from patient prior to participation in the study (if the patient is unable to express in writing: consent by a trusted person).
5. Patients should be able to call and to answer to a phone call or to be with a relative who can help him to call or to answer questions notably raised by a medical staff belonging to the investigational site

Exclusion Criteria:

1. Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency, ICU admission)
2. Patient requiring ICU admission,
3. Estimated Glomerular Filtration Rate \< 30 ml/min,
4. Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, transplant, myeloma, lymphoma, known HIV and CD4\<200/mm3),
5. Exacerbation of chronic obstructive pulmonary disease,
6. Life-threatening state expected to lead to possible imminent death,
7. Suspected atypical bacteria requiring combined antibiotics therapy,
8. Legionella suspected,
9. Subjects with clinical or epidemiological environment leading to suspect a healthcare associated pneumonia with antibiotic resistant pathogen (including long-term care facility)
10. Patient known to be colonized with Pseudomonas aeruginosa or Enterobacteriaceae in the respiratory tract,
11. Suspicion of aspiration pneumonia,
12. Administration of any antibiotic treatment for more than 24 hours before inclusion,
13. History of jaundice/hepatic impairment associated with amoxicillin/clavulanate acid,
14. History of bacterial pneumonia less than 1 month prior to study inclusion
15. History of hypersensitivity or allergy to beta-lactam or to any excipients included in study antibiotics,
16. Subject without health insurance,
17. Subject without home address or difficulty in terms of follow-up (vacation, job transfer, geographical distance, lack of motivation),
18. Patient under judicial protection,
19. Diagnosis confirmed of SAR-Cov2 infection (PCR Test, covid antigen rapid test, chest computed tomography (CT) scan),
20. Participation to another interventional study and having an exclusion period that is still in force during the screening phase or expected participation to another interventional study during participation to the CAPTAIN study

Primary outcomes:
measure: Non-inferiority
timeFrame: Day 30 after inclusion (=Day 1)
Secondary outcomes:
measure: Rates of early clinical response
timeFrame: Day 3 after inclusion (=Day 1)
measure: Clinical cure after the end of treatment
timeFrame: Within 30 days after inclusion (=Day 1) compared to baseline
measure: To investigate total duration of antibiotic treatment, i.e., the total number of days with antibiotics during the Day 30 follow-up after hospital admission
timeFrame: Day 30 after inclusion (=Day 1)
measure: To investigate all-cause mortality at Day 30 after hospital admission
timeFrame: Day 30 after inclusion (=Day 1)
measure: To investigate the rate of polymerase chain reaction (PCR)-positive Clostridium difficile among patients with diarrhea
timeFrame: Within 30 days after inclusion (=Day 1)
measure: To investigate in-hospital mortality
timeFrame: Within 30 days after inclusion (=Day 1)
measure: To investigate ICU transfer during the Day 30 follow-up
timeFrame: Day 30 after inclusion (=Day 1)
measure: To investigate CAP recurrence and hospital readmissions up to day 30 from hospital admission
timeFrame: Day 30 after inclusion (=Day 1)
measure: To investigate adverse events attributable to antibiotics up to day 30 from hospital admission
timeFrame: Day 30 after inclusion (=Day 1)
measure: To investigate compliance with the antibiotic treatment
timeFrame: Within 7 days after inclusion (=Day 1)
measure: To investigate length of hospital stay
timeFrame: Within 30 days after inclusion (=Day 1)
Other outcomes:
Locations:
city: Angers
country: France
facility: Chu Angers
city: Angers
country: France
facility: CHU Angers
city: Bobigny
country: France
facility: CHU Avicenne AP-HP
city: Bobigny
country: France
facility: CHU Avicenne AP-HP
city: Brest
country: France
facility: CHRU Brest
city: Brest
country: France
facility: CHRU Brest
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: La Tronche
country: France
facility: CHU Grenoble-Alpes
city: La Tronche
country: France
facility: CHU Grenoble-Alpes
city: Marseille
country: France
facility: Assistance Publique Hopitaux De Marseille
city: Nantes
country: France
facility: CHU de Nantes
city: Perigueux
country: France
facility: CH Perigueux
city: Toulouse
country: France
facility: CHRU - TOULOUSE Hôpital Purpan
city: Toulouse
country: France
facility: CHRU - TOULOUSE Hôpital Purpan
city: Toulouse
country: France
facility: CHRU TOULOUSE - Hôpital Rangueuil
city: Vannes
country: France
facility: Centre Hospitalier Bretagne Atlantique
Study officials:
affiliation: Toulouse UH
name: Frederic BALEN, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Toulouse UH
name: Guillaume MARTIN-BLONDEL, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Grenoble Hospital
name: Perrine DUMANOIR, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Grenoble Hospital
name: VIGLINO Damien, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Perigueux Hospital
name: Alexandrine VIDAL, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Angers UH
name: Delphine PLARD, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Angers UH
name: Rafaël MAHIEU, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Avicenne AP-HP
name: Anne-Laure FERAL-PIERSSENS, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Avicenne AP-HP
name: Frederic MECHAI, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Marseille Timone Hospital
name: Aurelie DAUMAS, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: CHD La Roche sur Yon
name: Dominique MERRIEN, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: CHD La Roche sur Yon
name: Sylvain LE GENTIL, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Vannes Hospital Bretagne Atlantic
name: Pierre BARSI, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Brest Hospital
name: Rozenn LE BERRE, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Brest Hospital
name: Sylvain JAFFUEL, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Toulouse UH
name: Xavier DUBUCS, Doctor
role: PRINCIPAL_INVESTIGATOR
References: