The C-reactive Protein (CRP) Point of Care Testing (POCT) Implementation to Adult Patients Presenting With Symptoms of the Acute Respiratory Tract Infection (ARTI) in Eight Primary Health Care (PHC) in Jakarta. (INA IMPACT-RTI)
Implementation of C-reactive Protein Point of Care Testing to Improve Antibiotic Use in Respiratory Tract Infection in the Indonesian Primary Health Care
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.
연구 개요
상세 설명
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.
- 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.
According to this design, all PHCs will experience two phases:
- Standard phase: Patients will be treated in accordance with current standards of care for acute respiratory tract infections without the use of CRP point of care testing (POCT).
- Implementation phase: Patients will be treated with usual care and with the addition of CRP point of care testing (POCT). The CRP POCT results will be provided to the treating physician as additional information to support clinical decision-making. The decision to prescribe antibiotics will remain based on the clinical decisions.
Data collection occurs at two key points:
- At the initial consultation (Day 0): Healthcare providers record patient complaints, physical exam findings, any test results (including CRP levels where applicable), diagnoses, treatments prescribed (including antibiotics), and referrals.
- At follow-up (Day 7): A follow-up assessment will be conducted via telephone to assess clinical status, any further antibiotic use, additional healthcare visits, and perceived recovery.
- Data management and analysis Direct access will be granted to authorized representatives from host institution for monitoring and/or audit of the study to ensure compliance with regulations. All data will be captured and processed anonymously. Data will be uploaded onto REDCap. Data will be retained for at least 5 years after end of study.
All study outcomes will be analyzed using multilevel logistic regression models to account for clustering at the level of the primary health care PHC sites, with individual patients included as a second random effect when appropriate. Fixed-effect covariates will include adjusting for stratification variables used and for key baseline characteristics identified a priori as potential confounders or found to be imbalanced between study arms, especially among participants with and without available day 7 follow-up data. Covariates will include:
- Patient-level variables: age, sex, presenting complaint category, and availability of day 7 follow-up data.
- Facility-level variables: average monthly outpatient attendance.
Outcomes assessed on day 0 will be analyzed in the per-protocol population, defined as participants with complete documentation of final treatment. Day 7 outcomes will be analyzed in both the per-protocol and complete-case populations (i.e., those with available follow-up data), and results will be reported for both unless otherwise specified.
Prespecified subgroup analyses will assess effect modification across sex, age categories, and presenting complaint types. All statistical analyses will be conducted using Stata software.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Robert Sinto, MD, DPhil
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
연구 연락처 백업
- 이름: Raph L Hamers, MD, PhD
- 전화번호: +622123599099
- 이메일: rhamers@oucru.org
연구 장소
-
-
-
Jakarta, 인도네시아, 11730
- 모병
- Cengkareng Public Health Center
-
연락하다:
- Robert Sinto, MD, DPhil
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
-
연락하다:
- Shafira Permata Radiani, SKM
- 전화번호: +622123599099
- 이메일: sradiani@oucru.org
-
Jakarta, 인도네시아, 12240
- 초대로 등록
- Kebayoran Lama Public Health Center
-
Jakarta, 인도네시아, 13220
- 모병
- Pulo Gadung Public Health Center
-
연락하다:
- Robert Sinto, MD, DPhil
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
-
연락하다:
- Shafira Permata Radiani, SKM
- 전화번호: +622123599099
- 이메일: sradiani@oucru.org
-
Jakarta, 인도네시아, 13310
- 모병
- Jatinegara Public Health Center
-
연락하다:
- Robert Sinto, MD, DPhil
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
-
연락하다:
- Shafira Permata Radiani, SKM
- 전화번호: +622123599099
- 이메일: sradiani@oucru.org
-
Jakarta, 인도네시아, 13440
- 모병
- Duren Sawit Public Health Center
-
연락하다:
- Robert Sinto, MD, DPhil
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
-
연락하다:
- Shafira Permata Radiani, SKM
- 전화번호: +622123599099
- 이메일: sradiani@oucru.org
-
Jakarta, 인도네시아, 13930
- 모병
- Cakung Public Health Center
-
연락하다:
- Robert Sinto, MD, DPhil
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
-
연락하다:
- Shafira Permata Radiani, SKM
- 전화번호: +622123599099
- 이메일: sradiani@oucru.org
-
Jakarta, 인도네시아, 14120
- 모병
- Cilincing Public Health Center
-
연락하다:
- Robert Sinto, MD, DPhil
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
-
연락하다:
- Shafira Permata Radiani, SKM
- 전화번호: +622123599099
- 이메일: sradiani@oucru.org
-
Jakarta, 인도네시아, 14260
- 모병
- Koja Public Health Center
-
연락하다:
- Shafira Permata Radiani, SKM
- 전화번호: +622123599099
- 이메일: sradiani@oucru.org
-
연락하다:
- Robert Sinto
- 전화번호: +622123599099
- 이메일: rsinto@oucru.org
-
-
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 특수 증상
- 할당: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
간섭 없음: Standard Group
Patients will be treated in accordance with current standards of care for acute respiratory tract infections without the use of CRP point of care testing (POCT).
|
|
|
실험적: Implementation group
Patients will be treated with usual care and with the addition of CRP point of care testing (POCT).
|
Patients will be treated with usual care and with the addition of CRP point-of-care testing (POCT). The testing process will use the ACTIM CRP® test and comply with ISO 13485 and MDSAP 13845 quality management system standards and is CE-marked for in vitro diagnostic use. CRP testing will be conducted by a trained research assistant who will be assigned on-site at each primary health care. The CRP POCT results will be provided to the treating physician as additional information to support clinical decision-making. The decision to prescribe antibiotics will remain based on the clinical decisions. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Compare the proportion of patients prescribed antibiotics at initial consultation in implementation (CRP tested) versus standard (non-CRP tested) groups
기간: 7 days
|
The proportion of enrolled adult patients with ARTI who were prescribed any antibiotic during their first consultation at a participating PHC site.
|
7 days
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Measure proportion of patients with antibiotic prescription stratified by CRP level in implementation (CRP tested) versus standard (non-CRP tested) groups
기간: 7 days
|
Proportion of patients prescribed an antibiotic in the implementation arm with:
|
7 days
|
|
Compare proportion of patients with hospitalization within 7 days in implementation (CRP tested) versus standard (non-CRP tested) groups
기간: 7 days
|
The proportion of patients who were hospitalized at any point within 7 days following the initial consultation at a study facility, regardless of referral status.
|
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
기간: 7 days
|
The proportion of patients who made an unplanned visit to any health facility (public or private) for the same or worsening illness within 7 days after the initial consultation.
Scheduled follow-up visits or referrals are not included.
|
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
기간: 7 days
|
The proportion of patients who report subjective worsening of their clinical condition on day 7 following the initial consultation. This includes:
|
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
기간: 7 days
|
The proportion of patients who receive any additional antibiotic medication within 7 days following the initial consultation. This includes:
|
7 days
|
공동 작업자 및 조사자
협력자
수사관
- 수석 연구원: Robert Sinto, MD, DPhil, Dr Cipto Mangunkusumo General Hospital
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- OUCRU-ID.2025.006
- 230GRSE10IND (기타 보조금/기금 번호: MORU - OUCRU Discovery Research Academy)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .