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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 326
- 试验地点
- 14
- 主要终点
- Non-inferiority
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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,
- •Administration of any antibiotic treatment for more than 24 hours before inclusion,
- •History of jaundice/hepatic impairment associated with amoxicillin/clavulanate acid,
- •History of bacterial pneumonia less than 1 month prior to study inclusion
- •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),
- •Patient under judicial protection,
- •Diagnosis confirmed of SAR-Cov2 infection (PCR Test, covid antigen rapid test, chest computed tomography (CT) scan),
- •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
研究组 & 干预措施
Amoxicillin
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.
干预措施: Amoxicillin (Drug)
Amoxicillin/clavulanate
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
干预措施: Amoxicillin/clavulanate (Drug)
结局指标
主要结局
Non-inferiority
时间窗: Day 30 after inclusion (=Day 1)
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
次要结局
- To investigate in-hospital mortality(Within 30 days after inclusion (=Day 1))
- To investigate ICU transfer during the Day 30 follow-up(Day 30 after inclusion (=Day 1))
- To investigate CAP recurrence and hospital readmissions up to day 30 from hospital admission(Day 30 after inclusion (=Day 1))
- To investigate adverse events attributable to antibiotics up to day 30 from hospital admission(Day 30 after inclusion (=Day 1))
- To investigate compliance with the antibiotic treatment(Within 7 days after inclusion (=Day 1))
- To investigate length of hospital stay(Within 30 days after inclusion (=Day 1))
- 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))
- Analysis of sensitivity todiscordance(Within 30 days after inclusion (=Day 1))