Antibiotic Stewardship Through CRP-guided Antibiotic Treatment for Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,184
- 试验地点
- 1
- 主要终点
- Antibiotic duration
研究概览
简要总结
Objectives:
To determine whether CRP-guided antibiotic treatment for managing AECOPD in adult patients attending Emergency Departments leads to reduced antibiotic duration, without non-inferior COPD health status with usual care.
Hypothesis to be tested:
(i) The antibiotic duration in AECOPD patients will be significantly lower for CRP-guided antibiotic discontinuation than usual care; and (ii) COPD health status as measured by the Clinical COPD Questionnaire has no statistically significant difference between two groups.
Design and subjects:
Multi-center, single-blind, open-label, randomized, combined superiority (antibiotic duration) and non-inferiority (COPD health status) trial in 1,184 adult AECOPD patients presented to A&E.
Instruments:
Clinical COPD Questionnaire and EuroQol-5D
Interventions:
Both intervention and control groups follow usual care with GOLD strategy. The intervention group will be recommended to test for serum CRP daily. Antibiotic prescription is considered when CRP >5mg/dL. Once CRP has declined to <5mg/dL and the patient was afebrile for past 48 hours, antibiotic discontinuation will be considered.
Communication with Receiving Ward Staffs:
Participants in the study may transfer to another departments after treatment/ care in A&E. The following communication would be conducted:
- A handover note that informs the receiving ward staffs about patients' enrolment to the trial, group assignment, and previous treatments given in A&E. The note would also suggest the investigations for the receiving ward staffs.
- Telephone handover about intervention group and investigations of the study, and treatments given in A&E to ward.
Main outcome measures:
The antibiotic duration (total number of antibiotic days) within 28 days and recovery in terms of COPD health status (Clinical COPD Questionnaire total scores) within 14 days from randomisation.
Data analysis:
Intention-to-treat and cost-effectiveness analyses will be performed. The outcome assessors and data analysts will be blinded to group allocation.
Expected results:
The intervention group will exhibit reduction in antibiotic duration at 4-weeks, without negatively impacting on COPD health status, compared with the control group.
详细描述
Introduction
Multiple small successes against antimicrobial resistance are urgently needed. The Global Action Plan in 2015 reiterated the importance of tackling antimicrobial abuse and bacterial resistance, which is jeopardizing our ability to manage infectious diseases. Antimicrobial resistance is predicted to cause catastrophic economic impacts in the next 10 years by putting 24 million people into extreme poverty, and will lead to an estimated 10 million deaths annually by 2050. Evidence has shown that an extended course of antibiotics is by no means superior to a shorter one. The over-prescription of broad-spectrum antibiotics in both hospitals and primary care has become a global concern and has driven initiatives to safeguard patient safety through the responsible use of antibiotics as treatments and prophylaxis. In a recent analysis, 55% of pathogenic bacteria identified in sputum culture from AECOPD patients in Hong Kong has demonstrated resistance to at least one antibiotic. Even relatively small changes in prescribing are likely to have beneficial effects on resistance at a population level.
There is a need for improved decision-making for antibiotic prescription in AECOPD. International Guideline (GOLD strategy) recommends empirical broad-spectrum antibiotics covering common respiratory pathogens for acute management, based on self-reported subjective AECOPD features, and the risk of bacterial infection. Evidence for the optimal duration of antibiotic treatment is unclear. Antibiotics are reportedly used in 87% of AECOPD patients in US, 74% in UK, and 96% in Hong Kong. AECOPD contributes 21,000 episodes of local hospital admission and readmission in 2019. AECOPD is triggered by infectious and non-infectious precipitants, although 30% are undetermined. Bacterial infection accounts for only 35%-57% among the infected. Inappropriate antibiotic usage may increase the risks of adverse events such as Clostridioides difficile colitis. Moreover, this confers a predisposition to airway colonization by multidrug-resistant bacteria, increasing COPD patients' risk of carrying resistant organisms in their lungs and then exacerbation or progression of pneumonia. The investigators have found that 55% of pathogenic bacteria identified from sputum culture among AECOPD patients were resistant to 1 or more antibiotics.
C-Reactive Protein (CRP) may help physicians make more appropriate antibiotic decisions. C-Reactive Protein (CRP) is an acute-phase reactant secreted by the liver in response to bacterial infections. It is synthesized within 4 to 6 hours after tissue injury/inflammation, and levels double every 8 hours, peaking at about 36 hours. CRP is significantly elevated in patients with bacterial infection, representing better treatment effect with antibiotics at elevated CRP values. CRP has been shown to be highly selective for AECOPD and it has excellent diagnostic accuracy when interpreted together with AECOPD symptomatology. Elevated CRPs (>5 mg/dL) in hospitalised AECOPD patients are associated with chest infections, implying a treatment role for antibiotics in this group. Yet antibiotics did not offer higher benefit over placebo among those with normal CRP level.
Work done by others
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Being diagnosed with active AECOPD (AECOPD is defined as an event in the natural course of a disease characterized by a change in baseline dyspnoea, cough, and/or sputum that is beyond the normal day-to-day variations with acute onset, which may warrant a change in regular medication in patients with underlying COPD).
- •Known COPD in their medical records.
- •Age 40 years or older.
- •Able to provide informed consent in Cantonese, Mandarin, or English
- •Able to complete the questionnaires during the study period (i.e. 6 months after randomisation)
排除标准
- •Patients will be excluded if any ONE of the following are present:
- •Pre-treatment with systemic corticosteroids for the present exacerbation.
- •Pre-treatment with any antibiotics for the present exacerbation, any concurrent infection or prophylaxis.
- •Known clinical stroke in past 6 months
- •Patients with high suspicion of active AECOPD mimics:
- •Congestive heart failure
- •Bronchiectasis
- •Pulmonary embolism
- •Pneumothorax
- •Atrial fibrillation / flutter
- •Lung comorbidities:
- •Cystic fibrosis
- •Tuberculosis
- •Unresolved lung malignancy
- •Progression or new radiographic abnormalities on the chest X-ray.
- •Immunodeficiency disorders such as AIDS, humoral immune defect, ciliary dysfunction etc., and the use of immunosuppressive drugs for more than 28 days.
- •Active inflammatory condition (e.g. flare up of rheumatoid arthritis, gout or polymyalgia rheumatica) or concurrent infection at another site (e.g. UTI, cellulitis) that is likely to produce a systemic response
- •Currently pregnant
- •NEWS2 score of ≥3
结局指标
主要结局
Antibiotic duration
时间窗: 28 days, 4 weeks
Mean antibiotic duration (in days) within 28-days for AECOPD after randomization, measured at the end of each week, using audio/video call until 28 days post randomization. Medication record is also reviewed at 4-weeks post randomization to capture prescription of antibiotics related or unrelated to AECOPD.
COPD health status by Clinical COPD Questionnaire (CCQ) total scores
时间窗: 14 days, 2 weeks
The CCQ is a validated and reliable 10-item, self-administered questionnaire. The CCQ consists of three subdomains: symptoms, functional state and mental state. Items are scored on a Likert scale (range 0-60). The final score is the sum of all items divided by 10; separate scores for all three domains can be calculated. Higher scores indicate a worse health status.
次要结局
- Prevalence of potentially pathogenic bacteria cultured from sputum at 4 weeks and the proportion of bacteria that are resistant(4-week)
- Use of other COPD treatments including orally administered steroids(4-week)
- Primary and secondary care consultations, including hospitalisations(4-week & 6-month)
- Costs (total HA cost) and cost-effectiveness(6 month)
- Incidence of pneumonia (measured by patient and medical record)(4-week & 6-month)
- Disease-specific, health-related quality of life over time measured using the Chronic Respiratory Disease Questionnaire Self-Administered Standardized(CRQ-SAS)(6-month)
- Adverse effects potentially attributable to antibiotics prescribed for the exacerbation(Weekly for 4 weeks)
- Prevalence of commensal organisms cultured from sputum at 4 weeks and the proportion of bacteria that are resistant(4-week)
- All-cause antibiotic consumption(During the first 4 weeks post randomisation)
- General health status measured by European Quality of Life-5 Dimensions 5-Level questionnaire (EQ-5D-5L).(Weekly for 4 weeks)
- Antibiotic prescribing(Up to first 4 weeks)
研究者
Dr. Wai, Ka Chung Abraham
Clinical Assistant Professor
The University of Hong Kong