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BMC Emergency Medicine
Published in: BMC Emergency Medicine 1/2017

Open Access 01-12-2017 | Study protocol

Design and rationale of the Procalcitonin Antibiotic Consensus Trial (ProACT), a multicenter randomized trial of procalcitonin antibiotic guidance in lower respiratory tract infection

Authors: David T. Huang, Derek C. Angus, Chung-Chou H. Chang, Yohei Doi, Michael J. Fine, John A. Kellum, Octavia M. Peck-Palmer, Francis Pike, Lisa A. Weissfeld, Jonathan Yabes, Donald M. Yealy, on behalf of the ProACT Investigators

Published in: BMC Emergency Medicine | Issue 1/2017

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Abstract

Background

Overuse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns.

Methods

The Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection.

Discussion

We describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation.

Trial registration

ClinicalTrials.gov NCT02130986. Registered May 1, 2014.
Appendix
Available only for authorised users
Literature
1.
Magill SS, Edwards JR, Beldavs ZG, Dumyati G, Janelle SJ, Kainer MA, Lynfield R, Nadle J, Neuhauser MM, Ray SM, et al. Prevalence of antimicrobial use in US acute care hospitals, May-September 2011. JAMA. 2014;312:1438–46.CrossRefPubMed
2.
Shapiro DJ, Hicks LA, Pavia AT, Hersh AL. Antibiotic prescribing for adults in ambulatory care in the USA, 2007-09. J Antimicrob Chemother. 2014;69:234–40.CrossRefPubMed
3.
Nathan C, Cars O. Antibiotic resistance--problems, progress, and prospects. N Engl J Med. 2014;371:1761–3.CrossRefPubMed
4.
Marston HD, Dixon DM, Knisely JM, Palmore TN, Fauci AS. Antimicrobial Resistance. JAMA. 2016;316:1193–204.CrossRefPubMed
5.
Metlay JP, Camargo CA Jr, MacKenzie T, McCulloch C, Maselli J, Levin SK, Kersey A, Gonzales R. Cluster-randomized trial to improve antibiotic use for adults with acute respiratory infections treated in emergency departments. Ann Emerg Med. 2007;50:221–30.CrossRefPubMed
6.
Little P, Rumsby K, Kelly J, Watson L, Moore M, Warner G, Fahey T, Williamson I. Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial. JAMA. 2005;293:3029–35.CrossRefPubMed
7.
Ranji SR, Steinman MA, Shojania KG, Sundaram V, Lewis R, Arnold S, Gonzales R. Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies (Vol. 4: Antibiotic Prescribing Behavior). (2006).
8.
Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM Jr, Finkelstein JA, Gerber JS, Hyun DY, Linder JA, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315:1864–73.CrossRefPubMed
9.
Muller B, White JC, Nylen ES, Snider RH, Becker KL, Habener JF. Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab. 2001;86:396–404.PubMed
10.
Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341:515–8.CrossRefPubMed
11.
Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39:206–17.CrossRefPubMed
12.
Muller B, Harbarth S, Stolz D, Bingisser R, Mueller C, Leuppi J, Nusbaumer C, Tamm M, Christ-Crain M. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10.CrossRefPubMedPubMedCentral
13.
Huang DT, Weissfeld LA, Kellum JA, Yealy DM, Kong L, Martino M, Angus DC, GenIMS Investigators. Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia. Ann Emerg Med. 2008;52(1):48–58.e2. doi:10.​1016/​j.​annemergmed.​2008.​01.​003. Epub 2008 Mar 17.
14.
Luyt CE, Guerin V, Combes A, Trouillet JL, Ayed SB, Bernard M, Gibert C, Chastre J. Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am.J Respir. Crit Care Med. 2005;171:48–53.CrossRef
15.
Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302:1059–66.CrossRefPubMed
16.
Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B. Procalcitonin-guidance of antibiotic therapy in community-acquired pneumonia - A randomized trial. Am J Respir Crit Care Med. 2006;174(1):84–93. Epub 2006 Apr 7. https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​16603606.
17.
Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004;363:600–7.CrossRefPubMed
18.
Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, Huber P, Muller B, Tamm M. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007;131:9–19.CrossRefPubMed
19.
Yealy DM, Fine MJ. Measurement of serum procalcitonin: a step closer to tailored care for respiratory infections? JAMA. 2009;302:1115–6.CrossRefPubMed
20.
Schuetz P, Christ-Crain M, Wolbers M, Schild U, Thomann R, Falconnier C, Widmer I, Neidert S, Blum CA, Schonenberger R, et al. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial. BMC Health Serv Res. 2007;7:102.CrossRefPubMedPubMedCentral
21.
Pitts SR, Pines JM, Handrigan MT, Kellermann AL. National trends in emergency department occupancy, 2001 to 2008: effect of inpatient admissions versus emergency department practice intensity. Ann Emerg Med. 2012;60:679–86.CrossRefPubMed
22.
Armour, S. U.S. Emergency-room visits keep climbing. Wall Street J. 2015. 1-24-2017. Ref Type: Magazine Article.
23.
Emanuel EJ, Pearson SD. Physician autonomy and health care reform. JAMA. 2012;307:367–8.PubMed
24.
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27–72.CrossRefPubMed
25.
Center for Disease Control and Prevention. Number and rate of discharges from short-stay hospitals and of days of care, with average length of stay and standard error, by selected first-listed diagnostic categories: United States, 2010. 2012. Ref Type: Online Source.
26.
27.
Branche AR, Walsh EE, Vargas R, Hulbert B, Formica MA, Baran A, Peterson DR, Falsey AR. Serum procalcitonin measurement and viral testing to guide antibiotic use for respiratory infections in hospitalized adults: a randomized controlled trial. J Infect Dis. 2015;212:1692–700.CrossRefPubMedPubMedCentral
28.
29.
30.
van Dissel JT. Procalcitonin and other markers of infection. What should be their role in clinical practice? Clin Microbiol Infect. 2002;8:70–3.CrossRefPubMed
31.
32.
National Institute for Health and Care Excellence. Assessment of community-acquired pneumonia. Last updated 12/23/2016. 2016. 3–2-2017. Ref Type: Electronic Citation.
33.
U.S.Food and Drug Administration. FDA clears test to help manage antibiotic treatment for lower respiratory tract infections and sepsis. 2017. 3–2-2017. Ref Type: Online Source.
34.
Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. 2008;148:295–309.CrossRefPubMed
35.
36.
Piaggio G, Elbourne DR, Pocock SJ, Evans SJ, Altman DG. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA. 2012;308:2594–604.CrossRefPubMed
37.
38.
2007. Expert Panel Report 3 (EPR-3): Guidelines for the diagnosis and management of asthma-summary report 38. J Allergy Clin Immunol. 120:S94–138.
39.
40.
Harris AM, Hicks LA, Qaseem A. Appropriate antibiotic use for acute respiratory tract infection in adults: advice for high-value care from the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2016;164:425–34.CrossRefPubMed
41.
Meisner M, Tschaikowsky K, Schnabel S, Schmidt J, Katalinic A, Schuttler J. Procalcitonin--influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations. Eur J Clin Chem Clin Biochem. 1997;35:597–601.PubMed
42.
Riedel S, Melendez JH, An AT, Rosenbaum JE, Zenilman JM. Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am J Clin Pathol. 2011;135:182–9.CrossRefPubMed
43.
Schuetz, P., M. Christ-Crain, A. R. Huber, and B. Muller. 2009. Long-term stability of procalcitonin in frozen samples and comparison of Kryptor(R) and VIDAS(R) automated immunoassays. Clin.Biochem.
44.
45.
46.
47.
Hedelius R, Daheshia M, Seda G. Thermal stability evaluation of procalcitonin, A biomarker and mediator of bacterial infection. Am J Respir Crit Care Med. 2013;187:A5984. Ref Type: Abstract.
48.
Yealy DM, Auble TE, Stone RA, Lave JR, Meehan TP, Graff LG, Fine JM, Obrosky DS, Edick SM, Hough LJ, et al. The emergency department community-acquired pneumonia trial: Methodology of a quality improvement intervention. Ann Emerg Med. 2004;43:770–82.CrossRefPubMed
49.
Yealy DM, Auble TE, Stone RA, Lave JR, Meehan TP, Graff LG, Fine JM, Obrosky DS, Mor MK, Whittle J, et al. Effect of increasing the intensity of implementing pneumonia guidelines: a randomized, controlled trial. Ann Intern Med. 2005;143:881–94.CrossRefPubMed
50.
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120:c179–84.PubMed
51.
Huang, D. T., L. A. Weissfeld, J. A. Kellum, D. M. Yealy, L. Kong, M. Martino, and D. C. Angus. 2008. Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia. Ann. Emerg. Med.
52.
Lindenauer PK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303:2359–67.CrossRefPubMed
53.
Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375:463–74.CrossRefPubMed
54.
Montori VM, Devereaux PJ, Adhikari NK, Burns KE, Eggert CH, Briel M, Lacchetti C, Leung TW, Darling E, Bryant DM, et al. Randomized trials stopped early for benefit: a systematic review. JAMA. 2005;294:2203–9.CrossRefPubMed
55.
Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–2.CrossRefPubMed
56.
Dawson L, Zarin DA, Emanuel EJ, Friedman LM, Chaudhari B, Goodman SN. Considering usual medical care in clinical trial design. PLoS Med. 2009;6:e1000111.CrossRefPubMedPubMedCentral
57.
Barley EA, Quirk FH, Jones PW. Asthma health status measurement in clinical practice: validity of a new short and simple instrument. Respir Med. 1998;92:1207–14.CrossRefPubMed
58.
Lin CY, Farrell MH, Lave JR, Angus DC, Barnato AE. Organizational determinants of hospital end-of-life treatment intensity. Med Care. 2009;47:524–30.CrossRefPubMedPubMedCentral
Metadata
Title
Design and rationale of the Procalcitonin Antibiotic Consensus Trial (ProACT), a multicenter randomized trial of procalcitonin antibiotic guidance in lower respiratory tract infection
Authors
David T. Huang
Derek C. Angus
Chung-Chou H. Chang
Yohei Doi
Michael J. Fine
John A. Kellum
Octavia M. Peck-Palmer
Francis Pike
Lisa A. Weissfeld
Jonathan Yabes
Donald M. Yealy
on behalf of the ProACT Investigators
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Emergency Medicine / Issue 1/2017
Electronic ISSN: 1471-227X
DOI
https://doi.org/10.1186/s12873-017-0138-1

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