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

NCT06229288 | Recruiting Phase 3 DMC

• 1 other identifier: RC20_0015
• Study Type: interventional
• Target: 326
• Locations: 1 country
• Sites: 19

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.

Conditions

Community-acquired Pneumonia

Keywords

Community-acquired pneumonia; Amoxicillin; Amoxicillin/clavulanate

Outcome Measures

Primary Outcomes (1)

• Non-inferiority

  To investigate non-inferiority in terms of clinical efficacy among patients aged 65 years or older, hospitalized in a non-ICU ward for a CAP, and treated with narrow-spectrum (amoxicillin) versus broad-spectrum (amoxicillin/clavulanate) antimicrobial therapy, at Day 30 since hospital admission. To answer this question, clinical success rate at Day 30 since admission, defined as survival after completion of antibiotic treatment course, resolution of signs and symptoms of the infection (cough, purulent sputum production, dyspnea, or pleuritic chest pain) present at baseline with no new symptoms or complications attributable to CAP and no need for further antibacterial therapy will be determined

  Day 30 after inclusion (=Day 1)

Secondary Outcomes (12)

• Rates of early clinical response

  Day 3 after inclusion (=Day 1)

• Clinical cure after the end of treatment

  Within 30 days after inclusion (=Day 1) compared to baseline

• 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

  Day 30 after inclusion (=Day 1)

• To investigate all-cause mortality at Day 30 after hospital admission

  Day 30 after inclusion (=Day 1)

• To investigate the rate of polymerase chain reaction (PCR)-positive Clostridium difficile among patients with diarrhea

  Within 30 days after inclusion (=Day 1)

Study Arms (2)

Amoxicillin

EXPERIMENTAL

Amoxicillin is an antibiotic treatment approved in France and in many countries. The investigational medicinal products (IMPs) are: \- Amoxicillin capsules : Formulated as a 500 mg capsules for PO administration (commercially available). Description in IMP file. Amoxicillin capsules contain compendial excipients listed in the Summary Product Characteristics (SmPC), current version, and are kept in a cool dry place where the temperature stays at 15- 25°C. \- Amoxicillin IV vials : Formulated as a 1000 mg vial for IV administration (commercially available). Description in IMP file. Amoxicillin IV vials contain compendial excipient listed in the Summary Product Characteristics (SmPC), current version, and are kept in a cool dry place where the temperature stays at 15-25°C.

Drug: Amoxicillin

Amoxicillin/clavulanate

ACTIVE COMPARATOR

Amoxicillin/clavulanate is recommended by French and European guidelines for the treatment of patients aged 65 years or older, and hospitalized in a non-ICU ward, as reported above. The active comparators (IMPs) are: \- Amoxicillin/clavulanate tablets: Formulated as a tablet for PO administration (commercially available). Description in IMP file. Tablets contain 500 mg of amoxicillin trihydrate and 62.5 mg of clavulanate. Amoxicillin/clavulanate tablets contain compendial excipients listed in the Summary Product Characteristics (SmPC), current version, and are kept in a cool dry place where the temperature stays at 15-25°C. \- Amoxicillin/clavulanate vials Vials contain 1000 mg of amoxicillin and 200 mg of clavulanate. Description in IMP file. Amoxicillin/clavulanate vials contain compendial excipients listed in the Summary Product Characteristics (SmPC), current version, and are kept in a cool dry place where the temperature stays at 15-25°C

Drug: Amoxicillin/clavulanate

Interventions

Amoxicillin DRUG

Participants will be randomized to IV/oral amoxicillin or IV/oral amoxicillin/clavulanate for 5 days. Both agents are approved for treatment of respiratory infections. Amoxicillin PO: The dose is two capsule of 500 mg every 8 hours (that is 3 times daily). Amoxicillin IV: The dose is 1 g every 8 hours (that is 3 times daily)

Also known as: Experimental drug

Amoxicillin

Amoxicillin/clavulanate DRUG

Participants will be randomized to IV/oral amoxicillin or IV/oral amoxicillin/clavulanate for 5 days. Both agents are approved for treatment of respiratory infections. Amoxicillin/clavulanate PO: The dose is two tablets of 500 mg/62.5 mg every 8 hours (that is 3 times daily, approved standard dose) Amoxicillin/clavulanate IV: The dose is 1 g/200 mg every 8 hours (that is 3 times daily, approved standard dose)

Also known as: active comparator drug

Amoxicillin/clavulanate

Eligibility Criteria

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

You may qualify if:

• Patient aged 65 years or older with or without comorbidities defined by chronic diseases in immunocompetent patients,
• 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
• Patient understanding oral and written French
• 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).
• 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

You may not qualify if:

• Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency, ICU admission)
• Patient requiring ICU admission,
• Estimated Glomerular Filtration Rate \< 30 ml/min,
• Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, transplant, myeloma, lymphoma, known HIV and CD4\<200/mm3),
• Exacerbation of chronic obstructive pulmonary disease,
• Life-threatening state expected to lead to possible imminent death,
• Suspected atypical bacteria requiring combined antibiotics therapy,
• Legionella suspected,
• Subjects with clinical or epidemiological environment leading to suspect a healthcare associated pneumonia with antibiotic resistant pathogen (including long-term care facility)
• Patient known to be colonized with Pseudomonas aeruginosa or Enterobacteriaceae in the respiratory tract,
• Suspicion of aspiration pneumonia,
• History of jaundice/hepatic impairment associated with amoxicillin/clavulanate acid,
• History of hypersensitivity or allergy to beta-lactam or to any excipients included in study antibiotics,
• Subject without health insurance,
• Subject without home address or difficulty in terms of follow-up (vacation, job transfer, geographical distance, lack of motivation),

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (19)

CH Saint-Nazaire

Saint-Nazaire, France, 44600, France

RECRUITING

CH Saint-Nazaire

Saint-Nazaire, France, 44600, France

RECRUITING

Chu Angers

Angers, France

RECRUITING

CHU Angers

Angers, France

RECRUITING

CHU Avicenne AP-HP

Bobigny, France

RECRUITING

CHU Avicenne AP-HP

Bobigny, France

RECRUITING

CHRU Brest

Brest, France

RECRUITING

CHRU Brest

Brest, France

RECRUITING

CHD Vendée

La Roche-sur-Yon, France

RECRUITING

CHD Vendée

La Roche-sur-Yon, France

RECRUITING

CHU Grenoble-Alpes

La Tronche, France

RECRUITING

CHU Grenoble-Alpes

La Tronche, France

RECRUITING

Assistance Publique Hopitaux De Marseille

Marseille, France

RECRUITING

CHU de Nantes

Nantes, France

RECRUITING

CH Perigueux

Périgueux, France

RECRUITING

CHRU - TOULOUSE Hôpital Purpan

Toulouse, France

RECRUITING

CHRU - TOULOUSE Hôpital Purpan

Toulouse, France

RECRUITING

CHRU TOULOUSE - Hôpital Rangueuil

Toulouse, France

RECRUITING

Centre Hospitalier Bretagne Atlantique

Vannes, France

RECRUITING

MeSH Terms

Conditions

Community-Acquired Pneumonia

Interventions

Amoxicillin; Drugs, Investigational; Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Clavulanic Acid; Clavulanic Acids; Drug Combinations

Study Officials

• Frederic BALEN, Doctor

  Toulouse UH

  PRINCIPAL INVESTIGATOR

• Guillaume MARTIN-BLONDEL, Doctor

  Toulouse UH

  PRINCIPAL INVESTIGATOR

• Perrine DUMANOIR, Doctor

  Grenoble Hospital

  PRINCIPAL INVESTIGATOR

• VIGLINO Damien, Doctor

  Grenoble Hospital

  PRINCIPAL INVESTIGATOR

• Alexandrine VIDAL, Doctor

  Perigueux Hospital

  PRINCIPAL INVESTIGATOR

• Delphine PLARD, Doctor

  Angers UH

  PRINCIPAL INVESTIGATOR

• Rafaël MAHIEU, Doctor

  Angers UH

  PRINCIPAL INVESTIGATOR

• Anne-Laure FERAL-PIERSSENS, Doctor

  Avicenne AP-HP

  PRINCIPAL INVESTIGATOR

• Frederic MECHAI, Doctor

  Avicenne AP-HP

  PRINCIPAL INVESTIGATOR

• Aurelie DAUMAS, Professor

  Marseille Timone Hospital

  PRINCIPAL INVESTIGATOR

• Dominique MERRIEN, Doctor

  CHD La Roche sur Yon

  PRINCIPAL INVESTIGATOR

• Sylvain LE GENTIL, Doctor

  CHD La Roche sur Yon

  PRINCIPAL INVESTIGATOR

• Pierre BARSI, Doctor

  Vannes Hospital Bretagne Atlantic

  PRINCIPAL INVESTIGATOR

• Rozenn LE BERRE, Doctor

  Brest Hospital

  PRINCIPAL INVESTIGATOR

• Sylvain JAFFUEL, Doctor

  Brest Hospital

  PRINCIPAL INVESTIGATOR

• Xavier DUBUCS, Doctor

  Toulouse UH

  PRINCIPAL INVESTIGATOR

• Matthieu THIBAULT, Doctor

  Saint-Nazaire Hospital

  PRINCIPAL INVESTIGATOR

• BOISSEAU Dorothée, Doctor

  Saint-Nazaire Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emmanuel MONTASSIER, Professor

CONTACT

02 53 48 20 38; emmanuel.montassier@chu-nantes.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: Drug study, multi-centre, Phase 3, Controlled , Randomized, Open, Prospective

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: January 29, 2024
• Study Start: April 25, 2024
• Primary Completion (Estimated): May 25, 2027
• Study Completion (Estimated): May 25, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

FR (19)