General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial

Abstract

BackgroundMost patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status.Methods/designThis is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out.DiscussionIf shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD.Trial registrationISRCTN registry, ID: ISRCTN24346473. Registered on 20 August 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2144-8) contains supplementary material, which is available to authorized users.

C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT

“…This POCT required 1.5 µl of capillary blood (from a finger prick) and took < 4 minutes to provide a quantitative result. Other validated CE (Conformité Européene)-marked POCT devices and CRP cartridges giving a quantitative result within the range of the Alere Afinion POCT and requiring a similar volume of 38 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.…”

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

“…This multicenter, open-label, randomized, controlled trial was conducted from January 2015 through September 2017 in accordance with a previously published protocol, 33 which is available with the full text of this article at NEJM.org. The trial involved patients recruited from 86 general medical practices in the United Kingdom.…”

“…From these 9 practices, 208 patients were approached (a mean number of 23 patients approached per practice), which resulted in 1988 patients potentially assessed for eligibility (208/9 × 86); 138 were eligible (66.3%), which resulted in 1319 patients potentially eligible (138/9 × 86); and 109 (79.0%) were recruited. The main reasons for ineligibility were recent or current use of antibiotics (28 of 70 patients) or previous participation in the PACE study 33 Tables S13 and S14 in the Supplementary Appendix. There was no evidence of clinically important between-group differences in the proportion of patients who had primary care consultations (i.e., consultation with a primary care clinician outside a hospital) or secondary care consultations (i.e., planned consultation with a specialist in a hospital) during 6 months of follow-up (adjusted odds ratio, 1.39; 95% CI, 0.46 to 4.15); in the proportion of patients who received a diagnosis of pneumonia during the first 4 weeks of follow-up (adjusted odds ratio, 1.57; 95% CI, 0.28 to 8.84) and during 6 months of follow-up (adjusted odds ratio, 0.73; 95% CI, 0.29 to 1.82); and in health utility, with the scores averaged across the follow-up time points (adjusted mean difference in score, 0.04; 95% CI, −0.02 to 0.10).…”

Use of co-primary outcomes for trials of antimicrobial stewardship interventions

“…[8] The PACE study (General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease) determined the effectiveness of C-reactive Protein (CRP) point-of-care testing on safely reducing antibiotic use in patients presenting in primary care with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). [9] The study used two co-primary outcomes: i.) Antibiotic use for AECOPD within the first four-weeks post-randomisation; ii.)…”