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

Community-acquired Pneumonia Clinical Trial

— CAPTAIN  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06229288
• Other study ID #: RC20_0015
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 15, 2024
• Est. completion date: April 15, 2027

Study information

• Verified date: January 2024
• Source: Nantes University Hospital
• Contact: Emmanuel MONTASSIER, Professor
• Phone: 02 53 48 20 38
• Email: emmanuel.montassier[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 326
• Est. completion date: April 15, 2027
• Est. primary completion date: April 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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. Intercurrent infection requiring antibiotic treatment,

13. Administration of beta-lactam therapy for more than 24 hours before inclusion,

14. History of jaundice/hepatic impairment associated with amoxicillin/clavulanate acid,

15. History of bacterial pneumonia less than 1 month prior to study inclusion

16. History of hypersensitivity or allergy to beta-lactam or to any excipients included in study antibiotics,

17. Subject without health insurance,

18. Subject without home address or difficulty in terms of follow-up (vacation, job transfer, geographical distance, lack of motivation),

19. Patient under judicial protection,

20. Diagnosis confirmed of SAR-Cov2 infection (PCR Test, covid antigen rapid test, chest computed tomography (CT) scan),

21. 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

Related Conditions & MeSH terms

• Community-acquired Pneumonia
• Pneumonia

Intervention

Drug:
• Amoxicillin
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)
• Amoxicillin/clavulanate
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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rates of early clinical response	Early clinical response will be defined as survival with improvement of one or more levels relative to baseline in two or more symptoms of CAP and no worsening of one or more levels in other symptoms of community-acquired bacterial pneumonia, without receipt of rescue antibacterial therapy	Day 3 after inclusion (=Day 1)
Secondary	Clinical cure after the end of treatment	The proposed endpoint of clinical cure after the end of treatment is defined as resolution in relevant signs and symptoms reported at baseline, no worsening of symptoms, and no change in antimicrobial regimen	Within 30 days after inclusion (=Day 1) compared to baseline
Secondary	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	Days taking antibiotics from the first dose until the interruption of any antibiotic treatment during hospitalization and at late follow-up at Day 30 after hospital admission (to identify the use of any other antibiotic after hospital discharge defined as no IV, regain of autonomy identical to baseline, good clinical response and favorable evolution following initiation of antibiotics, other criteria left at the discretion of the investigators according to centers' practices)	Day 30 after inclusion (=Day 1)
Secondary	To investigate all-cause mortality at Day 30 after hospital admission	All-cause mortality at Day 30 after hospital admission	Day 30 after inclusion (=Day 1)
Secondary	To investigate the rate of polymerase chain reaction (PCR)-positive Clostridium difficile among patients with diarrhea	Number of positive polymerase chain reaction (PCR)-positive Clostridium difficile among patients with diarrhea	Within 30 days after inclusion (=Day 1)
Secondary	To investigate in-hospital mortality	Number of deaths during hospitalization	Within 30 days after inclusion (=Day 1)
Secondary	To investigate ICU transfer during the Day 30 follow-up	Number of patients transferred to the ICU during the Day 30 follow-up	Day 30 after inclusion (=Day 1)
Secondary	To investigate CAP recurrence and hospital readmissions up to day 30 from hospital admission	Number of hospital readmissions and CAP recurrence up to day 30 from hospital admission	Day 30 after inclusion (=Day 1)
Secondary	To investigate adverse events attributable to antibiotics up to day 30 from hospital admission	Number of adverse events attributable to antibiotics and number of days with adverse events up to day 30 from hospital admission	Day 30 after inclusion (=Day 1)
Secondary	To investigate compliance with the antibiotic treatment	Number of days of antibiotic treatment taken	Within 7 days after inclusion (=Day 1)
Secondary	To investigate length of hospital stay		Within 30 days after inclusion (=Day 1)