Antibiotic Stewardship in AECOPD Through CRP-Guided Management

NCT05286918 | Not Yet Recruiting

• 1 other identifier: AECOPD-WAI-21200182
• Study Type: interventional
• Target: 1,184
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Exacerbation of COPD; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Disease

Keywords

COPD; Antibiotics; C-Reactive Protein; Antibiotic stewardship; Emergency Department

Outcome Measures

Primary Outcomes (2)

• Antibiotic duration

  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.

  28 days, 4 weeks

• COPD health status by Clinical COPD Questionnaire (CCQ) total scores

  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.

  14 days, 2 weeks

Secondary Outcomes (11)

• Prevalence of potentially pathogenic bacteria cultured from sputum at 4 weeks and the proportion of bacteria that are resistant

  4-week

• Prevalence of commensal organisms cultured from sputum at 4 weeks and the proportion of bacteria that are resistant

  4-week

• Adverse effects potentially attributable to antibiotics prescribed for the exacerbation

  Weekly for 4 weeks

• All-cause antibiotic consumption

  During the first 4 weeks post randomisation

• Antibiotic prescribing

  Up to first 4 weeks

Study Arms (2)

The intervention (CRP-guided) group

EXPERIMENTAL

Standard usual care (following GOLD initiative, including bronchodilator, and systemic steroid). The attending doctor will use the CRP level to inform their decision to continue antibiotics around 3 hours from blood taking. These doctors will be provided pre-study training on CRP interpretation. Every day from randomization, serum CRP testing will be encouraged to take. Once CRP has declined to \<5mg/dL and the patient has remained afebrile for past 48 hours, antibiotic treatment will be reviewed for discontinuation. Otherwise, antibiotic treatment will be continued. A switch on the administration route, or a change of antibiotics due to adverse effect, allergy, or suggestion from culture result, is permitted according to in-patient physician's decisions. CRP will continue to be monitored daily upon discharge from that hospital (up to 28 days).

Procedure: The intervention (CRP-guided) group

The usual care (control) group

NO INTERVENTION

Patients in the control arm will be treated with usual care (GOLD initiative). No CRP would be measured.No CRP would be measured.

Interventions

The intervention (CRP-guided) group PROCEDURE

The attending doctor will use the CRP level to inform their decision to continue antibiotics around 3 hours from blood taking. These doctors will be provided pre-study training on CRP interpretation. Every day from randomization, serum CRP testing will be encouraged to take. Once CRP has declined to \<5mg/dL and the patient has remained afebrile for past 48 hours, antibiotic treatment will be reviewed for discontinuation. Otherwise, antibiotic treatment will be continued. A switch on the administration route, or a change of antibiotics due to adverse effect, allergy, or suggestion from culture result, is permitted according to in-patient physician's decisions. CRP will continue to be monitored daily upon discharge from that hospital (up to 28 days).

The intervention (CRP-guided) group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• Pneumonia
• Congestive heart failure
• Bronchiectasis
• Pulmonary embolism
• Pneumothorax
• Atrial fibrillation / flutter
• Lung comorbidities:
• Cystic fibrosis
• Tuberculosis
• Unresolved lung malignancy

Sponsors & Collaborators

• The University of Hong Kong: lead
• Food and Health Bureau, Hong Kong: collaborator

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Related Publications (24)

• Mendelson M, Matsoso MP. The World Health Organization Global Action Plan for antimicrobial resistance. S Afr Med J. 2015 Apr 6;105(5):325. doi: 10.7196/samj.9644. No abstract available.

  PMID: 26242647 BACKGROUND

• Strathdee SA, Davies SC, Marcelin JR. Confronting antimicrobial resistance beyond the COVID-19 pandemic and the 2020 US election. Lancet. 2020 Oct 10;396(10257):1050-1053. doi: 10.1016/S0140-6736(20)32063-8. Epub 2020 Sep 29. No abstract available.

  PMID: 33007218 BACKGROUND

• Tansarli GS, Mylonakis E. Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults. Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00635-18. doi: 10.1128/AAC.00635-18. Print 2018 Sep.

  PMID: 29987137 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

• Halpin DMG, Criner GJ, Papi A, Singh D, Anzueto A, Martinez FJ, Agusti AA, Vogelmeier CF. Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2021 Jan 1;203(1):24-36. doi: 10.1164/rccm.202009-3533SO.

  PMID: 33146552 BACKGROUND

• Stolbrink M, Bonnett LJ, Blakey JD. Antibiotics for COPD exacerbations: does drug or duration matter? A primary care database analysis. BMJ Open Respir Res. 2019 Sep 17;6(1):e000458. doi: 10.1136/bmjresp-2019-000458. eCollection 2019.

  PMID: 31681477 BACKGROUND

• Mathioudakis AG, Janssens W, Sivapalan P, Singanayagam A, Dransfield MT, Jensen JS, Vestbo J. Acute exacerbations of chronic obstructive pulmonary disease: in search of diagnostic biomarkers and treatable traits. Thorax. 2020 Jun;75(6):520-527. doi: 10.1136/thoraxjnl-2019-214484. Epub 2020 Mar 26.

  PMID: 32217784 BACKGROUND

• Pouwels KB, Dolk FCK, Smith DRM, Robotham JV, Smieszek T. Actual versus 'ideal' antibiotic prescribing for common conditions in English primary care. J Antimicrob Chemother. 2018 Feb 1;73(suppl_2):19-26. doi: 10.1093/jac/dkx502.

  PMID: 29490060 BACKGROUND

• Sapey E, Stockley RA. COPD exacerbations . 2: aetiology. Thorax. 2006 Mar;61(3):250-8. doi: 10.1136/thx.2005.041822.

  PMID: 16517585 BACKGROUND

• Al-Jaghbeer MJ, Justo JA, Owens W, Kohn J, Bookstaver PB, Hucks J, Al-Hasan MN. Risk factors for pneumonia due to beta-lactam-susceptible and beta-lactam-resistant Pseudomonas aeruginosa: a case-case-control study. Infection. 2018 Aug;46(4):487-494. doi: 10.1007/s15010-018-1147-z. Epub 2018 May 11.

  PMID: 29752649 BACKGROUND

• Hu L, Shi Q, Shi M, Liu R, Wang C. Diagnostic Value of PCT and CRP for Detecting Serious Bacterial Infections in Patients With Fever of Unknown Origin: A Systematic Review and Meta-analysis. Appl Immunohistochem Mol Morphol. 2017 Sep;25(8):e61-e69. doi: 10.1097/PAI.0000000000000552.

  PMID: 28885233 BACKGROUND

• Ding X, Wu X, Yu C, Hu S. Value of C-reactive protein measurement in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease. Med J Wuhan University. 2006;27(5):660-3.

  BACKGROUND

• Hurst JR, Donaldson GC, Perera WR, Wilkinson TM, Bilello JA, Hagan GW, Vessey RS, Wedzicha JA. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006 Oct 15;174(8):867-74. doi: 10.1164/rccm.200604-506OC. Epub 2006 Jun 23.

  PMID: 16799074 BACKGROUND

• Llor C, Moragas A, Hernandez S, Bayona C, Miravitlles M. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012 Oct 15;186(8):716-23. doi: 10.1164/rccm.201206-0996OC. Epub 2012 Aug 23.

  PMID: 22923662 BACKGROUND

• von Dach E, Albrich WC, Brunel AS, Prendki V, Cuvelier C, Flury D, Gayet-Ageron A, Huttner B, Kohler P, Lemmenmeier E, McCallin S, Rossel A, Harbarth S, Kaiser L, Bochud PY, Huttner A. Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial. JAMA. 2020 Jun 2;323(21):2160-2169. doi: 10.1001/jama.2020.6348.

  PMID: 32484534 BACKGROUND

• Huddy JR, Ni MZ, Barlow J, Majeed A, Hanna GB. Point-of-care C reactive protein for the diagnosis of lower respiratory tract infection in NHS primary care: a qualitative study of barriers and facilitators to adoption. BMJ Open. 2016 Mar 3;6(3):e009959. doi: 10.1136/bmjopen-2015-009959.

  PMID: 26940107 BACKGROUND

• Ko FW, Ip M, Chan PK, Ng SS, Chau SS, Hui DS. A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia. Respir Med. 2008 Aug;102(8):1109-16. doi: 10.1016/j.rmed.2008.03.019. Epub 2008 Jun 24.

  PMID: 18573648 BACKGROUND

• Brink A, Alsma J, Verdonschot RJCG, Rood PPM, Zietse R, Lingsma HF, Schuit SCE. Predicting mortality in patients with suspected sepsis at the Emergency Department; A retrospective cohort study comparing qSOFA, SIRS and National Early Warning Score. PLoS One. 2019 Jan 25;14(1):e0211133. doi: 10.1371/journal.pone.0211133. eCollection 2019.

  PMID: 30682104 BACKGROUND

• Gillespie D, Francis NA, Carrol ED, Thomas-Jones E, Butler CC, Hood K. Use of co-primary outcomes for trials of antimicrobial stewardship interventions. Lancet Infect Dis. 2018 Jun;18(6):595-597. doi: 10.1016/S1473-3099(18)30289-5. No abstract available.

  PMID: 29856347 BACKGROUND

• Kocks JW, Tuinenga MG, Uil SM, van den Berg JW, Stahl E, van der Molen T. Health status measurement in COPD: the minimal clinically important difference of the clinical COPD questionnaire. Respir Res. 2006 Apr 7;7(1):62. doi: 10.1186/1465-9921-7-62.

  PMID: 16603063 BACKGROUND

• Offen W, Chuang-Stein C, Dmitrienko A, et al. Multiple co-primary endpoints: medical and statistical solutions: a report from the multiple endpoints expert team of the Pharmaceutical Research and Manufacturers of America. Drug information journal. 2007;41(1):31-46.

  BACKGROUND

• Moher D, Chan AW. SPIRIT (standard protocol items: recommendations for interventional trials). Guidelines for Reporting Health Research: a user's manual. 2014:56-67.

  BACKGROUND

• Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials. 2010 Mar 24;11:32. doi: 10.1186/1745-6215-11-32.

  PMID: 20334632 BACKGROUND

• Butler CC, Gillespie D, White P, Bates J, Lowe R, Thomas-Jones E, Wootton M, Hood K, Phillips R, Melbye H, Llor C, Cals JWL, Naik G, Kirby N, Gal M, Riga E, Francis NA. C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations. N Engl J Med. 2019 Jul 11;381(2):111-120. doi: 10.1056/NEJMoa1803185.

  PMID: 31291514 RESULT

MeSH Terms

Conditions

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Emergencies

Interventions

Population Groups

Condition Hierarchy (Ancestors)

Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Officials

• Ka Chung Abraham WAI

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ka Chung Abraham WAI

CONTACT

(+852) 3917 9859; awai@hku.hk

Shi Yeow LEE

CONTACT

(+852) 9474 4035; shiyeow@hku.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: March 18, 2022
• Study Start: September 1, 2022
• Primary Completion: August 31, 2025
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)