Implementation of C-reactive Protein Point of Care Testing to Improve Antibiotic Use in Respiratory Tract Infection in the Indonesian Primary Health Care
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 2,544
- 试验地点
- 8
- 主要终点
- Compare the proportion of patients prescribed antibiotics at initial consultation in implementation (CRP tested) versus standard (non-CRP tested) groups
研究概览
简要总结
Antimicrobial resistance (AMR) has emerged as one of the most pressing global health challenges of the 21st century, particularly Indonesia is projected to be among the five nations globally with the highest percentage increase in antimicrobial consumption by 2030. Primary care settings represent the most critical implementation point for addressing inappropriate antibiotic use. ARTI constitutes the most common indication for antibiotic prescribing in primary care, yet much of this prescribing is inappropriate. The high frequency of inappropriate antibiotic prescribing for ARTI is particularly problematic because most of these infections are viral in nature and resolve spontaneously without antibiotic treatment. Studies across the Asia-Pacific region, including Indonesia, have documented antibiotic prescribing rates for upper respiratory tract infections ranging from 47% to 85%, indicating substantial overuse.
C-reactive protein (CRP) point-of-care test (POCT) has emerged as a promising, evidence-based implementation to reduce inappropriate antibiotic prescribing for acute respiratory infections in a systematic review of studies conducted primarily in primary care settings of high- and middle-income countries. However, the efficacy and safety of CRP POCT implementation have not been evaluated in Indonesian primary care settings, where healthcare infrastructure, patient populations, test acceptability, and prescribing practices may differ significantly from countries where studies have been conducted.
This research will fill a critical evidence gap by providing the first rigorous evaluation of CRP POCT in the Indonesian context. The findings will directly inform Indonesia's National Strategy for AMR Standard and provide evidence-based guidance for scaling antimicrobial stewardship implementations across Indonesian PHC sites. Reducing inappropriate antibiotic prescribing by implementing CRP will contribute to reduce the development of antimicrobial resistance, unnecessary adverse effects, and healthcare costs.
详细描述
- Representative sampling strategy and sample size calculation This research is aim to assess whether the implementation of CRP POCT reduces unnecessary antibiotic prescriptions for ARTI without increasing clinical failure by day seven. A total sample size of 2,544 patients is targeted, with an estimated 318 patients per PHC site and intraclass correlation coefficient of 0.002. This sample size is calculated using data from a prior study, where 7.7 percent of patients has clinical failure (proven by re-consultation in day 3) (pC = 0.077), the expected odds ratio comparing the new approach to standard is 1.25, a non-inferiority margin of 15%, equal implementation and standard ratio (k = 1), 80% power, a two-sided α = 0.05 and loss to follow up 10%.
The intracluster correlation coefficient (ICC) value of 0.002 used in the sample size calculation was derived from a previous stepped-wedge cluster randomized trial conducted in Tanzania. Although Tanzania and Indonesia are both classified as low- and middle-income countries (LMICs) and share several contextual similarities, such as resource constraints and primary health care-based service delivery, there are notable differences between the two settings, including the distribution of health facilities, workforce availability, and disease burden. As there are currently no published studies from Indonesia employing a similar cluster design in primary care settings, this ICC value was adopted as the most contextually comparable estimate available.
The 15% non-inferiority margin in this study represents a safety parameter for the implementation of CRP point-of-care testing. This margin refers to the acceptable difference in the proportion of patients who may require a follow-up visit to another healthcare facility and receive antibiotic treatment within seven days after the initial consultation. A 10-15% margin has been commonly applied in previous non-inferiority studies evaluating the clinical safety of CRP-guided antibiotic reduction strategies, reflecting an acceptable trade-off between reduced antibiotic use and clinical outcomes in mild acute respiratory infections. 2. Study procedures This study is designed as a pragmatic, stepped-wedge cluster design conducted across eight PHC sites in Jakarta, Indonesia. The PHC sites will be the unit of the study. Eight PHC sites will be purposively selected and assigned to either early or delayed implementation groups, forming the clusters in this stepped-wedge design. Given that conventional experimental designs may be perceived by PHC sites stakeholders as unethical in groups that will not receive CRP POCT during project time, we have opted to employ a pragmatic stepped-wedge cluster design. A stepped-wedge trial utilizes a crossover design with repeated observations over time and involves the allocation of clusters to different timepoints at which they begin receiving the implementation. This design allows for both within-cluster and between-cluster comparisons, thereby increasing statistical power and reducing the number of clusters needed compared to a traditional parallel cluster-design.
Eligible facilities are those averaging ≥30 ARTI consultations per week and willing to participate. At the study initiation, none of the clusters will receive implementation (CRP POCT). Patient enrolment, baseline assessments, and case report form-based data collection will be conducted continuously throughout this transition and implementation period. Every two weeks, there will be transitions of the assigned group of PHC sites from standard group to implementation group. Over a total duration of 18 weeks, all clusters eventually receive the implementation, allowing for both within- and between-cluster comparisons.
The order of primary health centers (PHCs) transitioning to the CRP POCT implementation phase (Group 1 to Group 8) will be determined consecutively based on the sequence in which each PHC sites provides formal consent to participate in the implementation, following allocation approval by the Jakarta Provincial Health Office.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged ≥18 years.
- •Presenting to the PHC site for the first consultation of the current episode of Acute-Respiratory Tract Infections (ARTI).
- •Reporting at least one of the following symptoms or clinical signs within the past 5 days: cough, rhinitis (e.g., sneezing, nasal congestion, or runny nose), pharyngitis (e.g., sore throat), shortness of breath, wheezing, chest pain, abnormal lung sounds on auscultation.
排除标准
- •Presenting with severe illness requiring referral to a higher-level healthcare facility (e.g., hospital).
- •Having known immunosuppression or chronic conditions, including but not limited to: HIV infection; chronic liver disease; history of malignancy; long-term use of systemic corticosteroids or other immunosuppressive therapies, as assessed by the healthcare worker or study team.
- •Having taken antibiotics prior to the visit to the primary health center.
结局指标
主要结局
Compare the proportion of patients prescribed antibiotics at initial consultation in implementation (CRP tested) versus standard (non-CRP tested) groups
时间窗: 7 days
The proportion of enrolled adult patients with ARTI who were prescribed any antibiotic during their first consultation at a participating PHC site.
次要结局
- Measure proportion of patients with antibiotic prescription stratified by CRP level in implementation (CRP tested) versus standard (non-CRP tested) groups(7 days)
- Compare proportion of patients with hospitalization within 7 days in implementation (CRP tested) versus standard (non-CRP tested) groups(7 days)
- Compare proportion of patients with unscheduled reattendance at any health facility by day 7 in implementation (CRP tested) versus standard (non-CRP tested) groups(7 days)
- Compare proportion of patients with subjective clinical worsening on day 7 following initial consultation in implementation (CRP tested) versus standard (non-CRP tested) groups(7 days)
- Compare proportion of measure additional antibiotic medication prescriptions within 7 days of the initial consultation in implementation (CRP tested) versus standard (non-CRP tested) groups(7 days)
研究者
Robert Sinto
Principle Investigator
Dr Cipto Mangunkusumo General Hospital