Implementation of CRP Point of Care Testing in Primary Care to Improve Antibiotic Targeting in Respiratory Illness (ICAT)

NCT03855215 | Completed

• 1 other identifier: 31HN
• Study Type: interventional
• Target: 2,606
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study will monitor and evaluate a quality improvement project - the introduction of commercially available lateral flow CRP tests with international regulatory approval, as a routine care service to improve the management of patients with acute respiratory infection (ARI) and reduce unnecessary antibiotic prescribing. No research staff will be present, and to minimise disruption and alteration of routine care, a waiver of written patient informed consent will be requested from the relevant ethical review boards, in accordance with the 2016 WHO/CIOMS International Guidance for Health-related Research Involving Humans8. Instead, patients in intervention clusters will be provided with information concerning how the test can assist healthcare workers in identifying when antibiotics are required, after which they will be free to refuse its use. The test selected for use in the study is the Actim® CRP test from Medix Biochemica (Finland; ISO certification ISO13485:2016). The test is a simple lateral flow device that uses capillary blood, obtained through a finger/heel puncture. The test provides a semi-quantitative indication of whether CRP concentrations are \<10mg/L, between 10-40mg/L, between 40-80mg/L, or above 80mg/L, in under 5 minutes with minimal training requirements. The test has been approved by the European regulatory body (CE-marking) as well as in 13 other countries around the world (including Switzerland, Norway, Iceland, Israel and Thailand) and has been validated for accuracy in previous publications.9,10 Our own research group has also confirmed the tests' accuracy in both laboratory and field environments, including their thermos-stability in a tropical climate (see annex). Neither Medix Biochemica nor any of its distributors, have had involvement with the design of the evaluation and our group has no conflict of interest with respect to the choice of the test. Main research question: Can point of care CRP tests introduced in routine primary healthcare reduce prescription of antibiotics for patients with acute respiratory infections, outside of the research context? Brief description of the intervention: The implementation of CRP point of care tests will be conducted at commune health centres (CHCs), the primary access point for public health services in Vietnam (CHC details are described in the Location section below). Prior to introduction of the tests, an educational session will be provided for local healthcare workers in both intervention and control arms about the role of antibiotics and AMR. After randomization, further training will be provided for healthcare workers in the intervention CHCs as to the use of CRP testing to guide antibiotic prescribing decisions. In the intervention CHCs, healthcare workers will be trained on the use and interpretation of CRP testing in ARI (detailed in section 5.4). Educational materials will also be developed for patients and care-givers regarding the value of CRP testing. Description of the population to be studied: This study will be conducted in the general population of Nam Dinh, a rural province in northern Vietnam. The test will be provided at CHCs and recommended for use in patients presenting with a chief complaint of ARI.

Conditions

Acute Respiratory Infection

Keywords

acute respiratory infection; ARI; antibiotic; Antimicrobial resistance; AMR; primary health care; CRP

Outcome Measures

Primary Outcomes (1)

• Proportion of patients aged 1 to 65 years, consulting for ARI, who are prescribed antibiotics in the two study arms

  Through study completion, the proportion of 1 year

Secondary Outcomes (12)

• The proportion of patients that consulted with ARI in the preceding year.

  Before the 1st recruitment

• Prescription rates for ARI patients in the preceding year.

  Before the 1st recruitment

• Proportion of patients indicated CRP test according to diagnosis, age, gender

  Through study completion, the data of 1 year

• Proportion of patients prescribed an antibiotic in the intervention arm with: a. CRP < 10 mg/L b. CRP from 10mg/L to 40mg/L c. CRP > 40mg/L

  Through study completion, the proportion of 1 year

• Proportion of patients receiving an antibiotic with the denominator being: a. All attendances b. All non-routine attendances

  Through study completion, the proportion of 1 year

Study Arms (2)

Intervention

EXPERIMENTAL

The ACTIM CRP Rapid Test (Medix, Biochemica) will be made available to the healthcare workers at the CHCs for use in patients in the target population. Printed guidance will be issued for the performance and interpretation of the CRP test results in terms of antibiotic guided treatment. The treating healthcare worker will decide based on their clinical evaluation whether or not to comply with this guideline. This guidance will also be discussed during the training sessions. The healthcare workers are recommended to use the CRP tests in all patients meeting the target population. The CRP cut-offs will be recommended below in the absence of warning signs of severity: CRP level \< 10 mg/L: no antibiotics are recommended CRP level from 10 mg/L to 40 mg/L: antibiotics are unlikely to be needed but should be considered in cases of high clinical concern CRP level \> 40 mg/L: antibiotics are recommended.

Diagnostic Test: ACTIM CRP Rapid Test (Medix, Biochemica)

Control

NO INTERVENTION

Working as routine

Interventions

ACTIM CRP Rapid Test (Medix, Biochemica) DIAGNOSTIC_TEST

The implementation of CRP point of care tests will be conducted at commune health centres (CHCs), the primary access point for public health services in Vietnam. In the intervention CHCs, healthcare workers will be trained on the use and interpretation of CRP testing in ARI. healthcare workers can decide to follow the test results or not.

Intervention

Eligibility Criteria

• Age: 1 Year - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients aged from 1 to under 65 years old
• First consultation with an acute respiratory infection diagnosed by the healthcare worker with at least 1 focal sign or symptom\*
• Symptoms lasting less than 7 days \* Focal signs and symptoms: (1) cough, (2) rhinitis (sneezing, nasal congestion, or runny nose), (3) pharyngitis (sore throat), (4) shortness of breath, (5) wheezing, (6) chest pain, or (7) auscultation abnormalities.

You may not qualify if:

• Patients requiring referral to a higher level facility based on the healthcare worker's clinical assessment
• immunosuppressed patients (known HIV, long term steroid use)
• those with a suspicion of tuberculosis or a non-respiratory tract illness

Sponsors & Collaborators

• Oxford University Clinical Research Unit, Vietnam: lead
• National Hospital for Tropical Diseases, Hanoi, Vietnam: collaborator

Study Sites (1)

National Hospital for Tropical Diseases

Hanoi, Vietnam

Location

Related Publications (16)

• Kaya Z, Kucukcongar A, Vuralli D, Emeksiz HC, Gursel T. Leukocyte populations and C-reactive protein as predictors of bacterial infections in febrile outpatient children. Turk J Haematol. 2014 Mar;31(1):49-55. doi: 10.4274/Tjh.2013.0057. Epub 2014 Mar 5.

  PMID: 24764729 BACKGROUND

• Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005 Feb 12-18;365(9459):579-87. doi: 10.1016/S0140-6736(05)17907-0.

  PMID: 15708101 BACKGROUND

• Shallcross LJ, Davies DS. Antibiotic overuse: a key driver of antimicrobial resistance. Br J Gen Pract. 2014 Dec;64(629):604-5. doi: 10.3399/bjgp14X682561. No abstract available.

  PMID: 25452508 BACKGROUND

• Greer RC, Intralawan D, Mukaka M, Wannapinij P, Day NPJ, Nedsuwan S, Lubell Y. Retrospective review of the management of acute infections and the indications for antibiotic prescription in primary care in northern Thailand. BMJ Open. 2018 Jul 30;8(7):e022250. doi: 10.1136/bmjopen-2018-022250.

  PMID: 30061442 BACKGROUND

• Aabenhus R, Jensen JU, Jorgensen KJ, Hrobjartsson A, Bjerrum L. Biomarkers as point-of-care tests to guide prescription of antibiotics in patients with acute respiratory infections in primary care. Cochrane Database Syst Rev. 2014 Nov 6;(11):CD010130. doi: 10.1002/14651858.CD010130.pub2.

  PMID: 25374293 BACKGROUND

• Do NT, Ta NT, Tran NT, Than HM, Vu BT, Hoang LB, van Doorn HR, Vu DT, Cals JW, Chandna A, Lubell Y, Nadjm B, Thwaites G, Wolbers M, Nguyen KV, Wertheim HF. Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial. Lancet Glob Health. 2016 Sep;4(9):e633-41. doi: 10.1016/S2214-109X(16)30142-5. Epub 2016 Aug 3.

  PMID: 27495137 BACKGROUND

• Althaus T, Greer RC, Swe MMM, Cohen J, Tun NN, Heaton J, Nedsuwan S, Intralawan D, Sumpradit N, Dittrich S, Doran Z, Waithira N, Thu HM, Win H, Thaipadungpanit J, Srilohasin P, Mukaka M, Smit PW, Charoenboon EN, Haenssgen MJ, Wangrangsimakul T, Blacksell S, Limmathurotsakul D, Day N, Smithuis F, Lubell Y. Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar: an open-label, randomised, controlled trial. Lancet Glob Health. 2019 Jan;7(1):e119-e131. doi: 10.1016/S2214-109X(18)30444-3.

  PMID: 30554748 BACKGROUND

• Evrard B, Roszyk L, Fattal S, Dastugue B, Sapin V. [Evaluation of rapid, semi-quantitative assay of C-reactive protein in whole blood, Actim CRP]. Ann Biol Clin (Paris). 2005 Sep-Oct;63(5):525-9. French.

  PMID: 16230290 BACKGROUND

• Brouwer N, van Pelt J. Validation and evaluation of eight commercially available point of care CRP methods. Clin Chim Acta. 2015 Jan 15;439:195-201. doi: 10.1016/j.cca.2014.10.028. Epub 2014 Oct 31.

  PMID: 25445415 BACKGROUND

• Senn N, Rarau P, Salib M, Manong D, Siba P, Rogerson S, Mueller I, Genton B. Use of antibiotics within the IMCI guidelines in outpatient settings in Papua New Guinean children: an observational and effectiveness study. PLoS One. 2014 Mar 13;9(3):e90990. doi: 10.1371/journal.pone.0090990. eCollection 2014.

  PMID: 24626194 BACKGROUND

• WHO. Integrated Management of Childhood Illness. Geneva, Switzerland; 2014

  BACKGROUND

• The World Health Organization. Integrated management of adolescent and adult illness: interim guidelines for first-level facility health workers at health centre and district outpatient clinic: acute care. 2009; Rev 3

  BACKGROUND

• Sim J, Dawson A. Informed consent and cluster-randomized trials. Am J Public Health. 2012 Mar;102(3):480-5. doi: 10.2105/AJPH.2011.300389. Epub 2012 Jan 19.

  PMID: 22390511 BACKGROUND

• Lubell Y, Blacksell SD, Dunachie S, Tanganuchitcharnchai A, Althaus T, Watthanaworawit W, Paris DH, Mayxay M, Peto TJ, Dondorp AM, White NJ, Day NP, Nosten F, Newton PN, Turner P. Performance of C-reactive protein and procalcitonin to distinguish viral from bacterial and malarial causes of fever in Southeast Asia. BMC Infect Dis. 2015 Nov 11;15:511. doi: 10.1186/s12879-015-1272-6.

  PMID: 26558692 BACKGROUND

• Do NTT, Vu TVD, Greer RC, Dittrich S, Vandendorpe M, Pham NT, Ta DN, Cao HT, Khuong TV, Le TBT, Duong TH, Nguyen TH, Cai NTH, Nguyen TQT, Trinh ST, van Doorn HR, Lubell Y, Lewycka S. 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. Lancet Infect Dis. 2023 Sep;23(9):1085-1094. doi: 10.1016/S1473-3099(23)00125-1. Epub 2023 May 22.

  PMID: 37230105 DERIVED

• Thi Thuy Do N, Greer RC, Lubell Y, Dittrich S, Vandendorpe M, Nguyen VA, Ngoc Thach P, Thi Dieu Ngan T, Van Kinh N, Hung Thai C, Dung LTK, Nguyen Thi Cam T, Nguyen TH, Nadjm B, van Doorn HR, Lewycka S. 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. BMJ Open. 2020 Dec 23;10(12):e040977. doi: 10.1136/bmjopen-2020-040977.

  PMID: 33361164 DERIVED

Related Links

• Ministry of Health. Vietnam health service delivery profile
• World Health Organisation. International ethical guidelines for health-related research involving humans.

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The implementation of CRP point of care tests will be conducted at commune health centres (CHCs), the primary access point for public health services in Vietnam (CHC details are described in the Location section below). Prior to introduction of the tests, an educational session will be provided for local healthcare workers in both intervention and control arms about the role of antibiotics and AMR. After randomization, further training will be provided for healthcare workers in the intervention CHCs as to the use of CRP testing to guide antibiotic prescribing decisions. In the intervention CHCs, healthcare workers will be trained on the use and interpretation of CRP testing in ARI (detailed in section 5.4). Educational materials will also be developed for patients and care-givers regarding the value of CRP testing.

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 26, 2019
• Study Start: June 1, 2020
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)