Implementation of point-of-care testing of C-reactive protein concentrations to improve antibiotic targeting in respiratory illness in Vietnamese primary care: a pragmatic cluster-randomised controlled trial.

BACKGROUND: In previous trials, point-of-care testing of C-reactive protein (CRP) concentrations safely reduced antibiotic use in non-severe acute respiratory infections in primary care. However, these trials were done in a research-oriented context with close support from research staff, which could have influenced prescribing practices. To better inform the potential for scaling up point-of-care testing of CRP in respiratory infections, we aimed to do a pragmatic trial of the intervention in a routine care setting. METHODS: We did a pragmatic, cluster-randomised controlled trial at 48 commune health centres in Viet Nam between June 1, 2020, and May 12, 2021. Eligible centres served populations of more than 3000 people, handled 10-40 respiratory infections per week, had licensed prescribers on site, and maintained electronic patient databases. Centres were randomly allocated (1:1) to provide point-of-care CRP testing plus routine care or routine care only. Randomisation was stratified by district and by baseline prescription level (ie, the proportion of patients with suspected acute respiratory infections to whom antibiotics were prescribed in 2019). Eligible patients were aged 1-65 years and visiting the commune health centre for a suspected acute respiratory infection with at least one focal sign or symptom and symptoms lasting less than 7 days. The primary endpoint was the proportion of patients prescribed an antibiotic at first attendance in the intention-to-treat population. The per-protocol analysis included only people who underwent CRP testing. Secondary safety outcomes included time to resolution of symptoms and frequency of hospitalisation. This trial is registered with ClinicalTrials.gov, NCT03855215. FINDINGS: 48 commune health centres were enrolled and randomly assigned, 24 to the intervention group (n=18 621 patients) and 24 to the control group (n=21 235). 17 345 (93·1%) patients in the intervention group were prescribed antibiotics, compared with 20 860 (98·2%) in the control group (adjusted relative risk 0·83 [95% CI 0·66-0·93]). Only 2606 (14%) of 18 621 patients in the intervention group underwent CRP testing and were included in the per-protocol analysis. When analyses were restricted to this population, larger reductions in prescribing were noted in the intervention group compared with the control group (adjusted relative risk 0·64 [95% CI 0·60-0·70]). Time to resolution of symptoms (hazard ratio 0·70 [95% CI 0·39-1·27]) and frequency of hospitalisation (nine in the intervention group vs 17 in the control group; adjusted relative risk 0·52 [95% CI 0·23-1·17]) did not differ between groups. INTERPRETATION: Use of point-of-care CRP testing efficaciously reduced prescription of antibiotics in patients with non-severe acute respiratory infections in primary health care in Viet Nam without compromising patient recovery. The low uptake of CRP testing suggests that barriers to implementation and compliance need to be addressed before scale-up of the intervention. FUNDING: Australian Government, UK Government, and the Foundation for Innovative New Diagnostics.

Outpatient antibiotic prescribing for acute respiratory infections in Vietnamese primary care settings by the WHO AWaRe (Access, Watch and Reserve) classification: An analysis using routinely collected electronic prescription data.

Background: This study aims to investigate patterns of antibiotic prescribing and to determine patient-specific factors associated with the choice of antibiotics by the World Health Organization's Access-Watch-Reserve (WHO AWaRe) class for acute respiratory infections (ARIs) in rural primary care settings in northern Vietnam. Methods: We retrospectively reviewed health records for outpatients who were registered with the Vietnamese Health Insurance Scheme, visited one of 112 commune health centres in 6 rural districts of Nam Dinh province, Vietnam during 2019, and were diagnosed with ARIs. Patient-level prescription data were collected from the electronic patient databases. We used descriptive statistics to investigate patterns of antibiotic prescribing, with the primary outcomes including total antibiotic prescriptions and prescriptions by WHO AWaRe group. We identified patient-specific factors associated with watch-group antibiotic prescribing through multivariable logistic regression analysis. Findings: Among 193,010 outpatient visits for ARIs observed in this study, 187,144 (97.0%) resulted in an antibiotic prescription, of which 172,976 (92.5%) were access-antibiotics, 10,765 (5.6%) were watch-antibiotics, 3366 (1.8%) were not-recommended antibiotics. No patients were treated with reserve-antibiotics. The proportion of watch-antibiotic prescription was highest amongst children under 5-years old (18.1%, compared to 9.5% for 5-17-years, 4.9% for 18-49-years, 4.3% for 50-64-years, and 3.7% for 65-and-above-years). In multivariable logistic regression, children, district, ARI-type, comobid chronic respiratory illness, and follow-up visit were associated with higher likelihood of prescribing watch-group antibiotics. Interpretation: The alarmingly high proportion of antibiotic prescriptions for ARIs in primary care, and the frequent use of watch-antibiotics for children, heighten concerns around antibiotic overuse at the community level. Antimicrobial stewardship interventions and policy attention are needed in primary care settings to tackle the growing threat of antibiotic resistance. Funding: This work was supported through Australian government and UK aid from the UK government funding to FIND (Foundation for Innovative New Diagnostics) grant number FO17-0015, in addition to a Wellcome Trust grant (213920/Z/18/Z), and an Oxford University Clinical Research Unit internal grant from the Wellcome Trust Africa Asia Programme core grant in Vietnam (106680/Z/14/Z).

Implementation of C-reactive protein point of care testing to improve antibiotic targeting in respiratory illness in Vietnamese primary care (ICAT): a study protocol for a cluster randomised controlled trial.

INTRODUCTION: C-reactive protein (CRP), a biomarker of infection, has been used widely in high-income settings to guide antibiotic treatment in patients presenting with respiratory illnesses in primary care. Recent trials in low- and middle-income countries showed that CRP testing could safely reduce antibiotic use in patients with non-severe acute respiratory infections (ARIs) and fever in primary care. The studies, however, were conducted in a research-oriented context, with research staff closely monitoring healthcare behaviour thus potentially influencing healthcare workers' prescribing practices. For policy-makers to consider wide-scale roll-out, a pragmatic implementation study of the impact of CRP point of care (POC) testing in routine care is needed. METHODS AND ANALYSIS: A pragmatic, cluster-randomised controlled trial, with two study arms, consisting of 24 commune health centres (CHC) in the intervention arm (provision of CRP tests with additional healthcare worker guidance) and 24 facilities acting as controls (routine care). Comparison between the treatment arms will be through logistic regression, with the treatment assignment as a fixed effect, and the CHC as a random effect. With 48 clusters, an average of 10 consultations per facility per week will result in approximately 520 over 1 year, and 24 960 in total (12 480 per arm). We will be able to detect a reduction of 12% to 23% or more in immediate antibiotic prescription as a result of the CRP POC intervention. The primary endpoint is the proportion of patient consultations for ARI resulting in immediate antibiotic prescription. Secondary endpoints include the proportion of all patients receiving an antibiotic prescription regardless of ARI diagnosis, frequency of re-consultation, subsequent antibiotic use when antibiotics are not prescribed, referral and hospitalisation. ETHICS AND DISSEMINATION: The study protocol was approved by the Oxford University Tropical Research Ethics Committee (OxTREC, Reference: 53-18), and the ethical committee of the National Hospital for Tropical Diseases in Vietnam (Reference:07/HDDD-NDTW/2019). Results from this study will be disseminated via meetings with stakeholders, conferences and publications in peer-reviewed journals. Authorship and reporting of this work will follow international guidelines. TRIAL REGISTRATION DETAILS: NCT03855215; Pre-results.