Procalcitonin Antibiotic Consensus Trial (ProACT) - Full Text View

Purpose

The ProACT study is a 5 year, multicenter study that will test the effect of implementation of a novel procalcitonin guideline on antibiotic use and adverse outcomes in emergency department (ED) patients with lower respiratory tract infection (LRTI).

Condition	Intervention
Lower Respiratory Tract Infection (LRTI)	Other: Procalcitonin level Other: Results of procalcitonin (PCT) level to treating clinician Other: Provide procalcitonin guideline to treating clinician Other: Telephone Visit


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Outcomes Assessor Primary Purpose: Treatment
Official Title:	Procalcitonin Antibiotic Consensus Trial (ProACT)

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics

U.S. FDA Resources

Further study details as provided by David T. Huang, MD, MPH, University of Pittsburgh:

Primary Outcome Measures:

Total antibiotic exposure days [ Time Frame: 30 days ]
Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30.
Combined endpoint of adverse outcomes that could be attributable to withholding antibiotics in LRTI [ Time Frame: 30 days ]

Secondary Outcome Measures:

Rate of antibiotic initiation by the initial ED clinician [ Time Frame: during initial ED visit ]


Enrollment:	1664
Actual Study Start Date:	November 3, 2014
Estimated Study Completion Date:	May 2018
Estimated Primary Completion Date:	July 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Procalcitonin (PCT) group Procalcitonin (PCT) level; Results of procalcitonin level to treating clinician; Provide procalcitonin guideline to treating clinician; Telephone Visit at Day 15 and Day 30	Other: Procalcitonin level A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion. Other Name: PCT level Other: Results of procalcitonin (PCT) level to treating clinician In the ED, we will quickly (<1 hour goal) provide clinicians the procalcitonin result. Other: Provide procalcitonin guideline to treating clinician Procalcitonin antibiotic guideline -- Procalcitonin level (ug/L) -- Bacterial etiology -- Recommendation < 0.1 -- Very unlikely -- Antibiotics strongly discouraged(1) 0.1 - 0.25 -- Unlikely -- Antibiotics discouraged(1) > 0.25 - 0.5 -- Likely -- Antibiotics recommended(2) > 0.5 -- Very likely -- Antibiotics strongly recommended(2) Initial antibiotics can be considered for critical illness, Legionella pneumophilia. Procalcitonin should be evaluated in context with all findings and the total clinical status; clinical judgment always necessary. For outpatients, antibiotic duration based on level (> 0.25-0.5 ug/L:3 days; > 0.5-1.0 ug/L:5 days; >1.0 ug/L:7 days). Physician follow-up is recommended. Other: Telephone Visit We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30
Active Comparator: Usual Care group Telephone Visit at Day 15 and Day 30	Other: Telephone Visit We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30

Arms

Assigned Interventions

Experimental: Procalcitonin (PCT) group

Procalcitonin (PCT) level; Results of procalcitonin level to treating clinician; Provide procalcitonin guideline to treating clinician; Telephone Visit at Day 15 and Day 30

Other: Procalcitonin level

A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion.

Other Name: PCT level

Other: Results of procalcitonin (PCT) level to treating clinician

In the ED, we will quickly (<1 hour goal) provide clinicians the procalcitonin result.

Other: Provide procalcitonin guideline to treating clinician

Procalcitonin antibiotic guideline --

Procalcitonin level (ug/L) -- Bacterial etiology -- Recommendation

< 0.1 -- Very unlikely -- Antibiotics strongly discouraged(1)

0.1 - 0.25 -- Unlikely -- Antibiotics discouraged(1)

> 0.25 - 0.5 -- Likely -- Antibiotics recommended(2)

> 0.5 -- Very likely -- Antibiotics strongly recommended(2)

Initial antibiotics can be considered for critical illness, Legionella pneumophilia. Procalcitonin should be evaluated in context with all findings and the total clinical status; clinical judgment always necessary.
For outpatients, antibiotic duration based on level (> 0.25-0.5 ug/L:3 days; > 0.5-1.0 ug/L:5 days; >1.0 ug/L:7 days). Physician follow-up is recommended.

Other: Telephone Visit

We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30

Active Comparator: Usual Care group

Telephone Visit at Day 15 and Day 30

Other: Telephone Visit

We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30

Detailed Description:

There is a need for improved decision-making for antibiotic prescription in acute suspected infection. Infections, particularly in the early stages, can have protean manifestations, often do not manifest with "classic" signs, and clinically overlap with non-infectious conditions. However, the imperative to quickly give antibiotics for bacterial infection has led to antibiotic overuse and resistance.

Strategies that combine novel diagnostics with therapeutics have improved decision-making in oncology, cardiology, and other fields. These strategies aim to identify those patients most likely to be helped or harmed by the therapeutic intervention and allow more individualized care. This approach takes diagnostics to the next level, by demanding a test not only measure well, but also that clinical care be improved by tying the test to a treatment strategy.

Procalcitonin, a novel biomarker of bacterial infection, may help physicians make more appropriate antibiotic decisions. Lower respiratory tract infection (LRTI) is an ideal trial population. LRTI accounts for a large proportion of antibiotic prescription, and exemplifies the imprecise clinical phenotype of infection.However, key questions of generalizability and safety preclude widespread application.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

≥ 18 years old
A primary clinical diagnosis in the ED of acute LRTI (< 28 days duration)
Clinician willing to consider procalcitonin in antibiotic decision-making

Exclusion Criteria:

Systemic antibiotics before ED presentation (All prophylactic antibiotic regimens, OR received >1 dose within 72 hours prior to ED presentation)
Current vasopressor use
Mechanical ventilation (via endotracheal tube)
Known severe immunosuppression
Accompanying non-respiratory infections
Known lung abscess or empyema
Chronic dialysis
Metastatic cancer
Surgery in the past 7 days (excluding minor surgery such as skin biopsy)
Incarcerated or homeless
Enrolled in ProACT in the past 30 days

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02130986

Locations


United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249
United States, Arizona
Maricopa Medical Center
Phoenix, Arizona, United States, 85008
United States, California
University of California at Irvine Medical Center
Orange, California, United States, 92868
United States, Connecticut
Norwalk Hospital
Norwalk, Connecticut, United States, 06856
United States, Maryland
University of Maryland/Baltimore
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Wayne State University/Detroit Receiving Hospital
Detroit, Michigan, United States, 48201
United States, Minnesota
Essentia Institute of Rural Health
Duluth, Minnesota, United States, 55805
United States, Ohio
The Ohio State University, College of Medicine
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Penn State Hershey College of Medicine; Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15261

Sponsors and Collaborators

University of Pittsburgh

National Institute of General Medical Sciences (NIGMS)

BioMérieux

Investigators


Principal Investigator:	David T Huang, MD MPH	University of Pittsburgh

More Information

Publications:

Meisner M. Biomarkers of sepsis: clinically useful? Curr Opin Crit Care. 2005 Oct;11(5):473-80. Review.

Schuetz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype? Swiss Med Wkly. 2009 Jun 13;139(23-24):318-26. doi: smw-12584. Review.

Müller B, White JC, Nylén 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 Jan;86(1):396-404.

Nylen E, Muller B, Becker KL, Snider R. The future diagnostic role of procalcitonin levels: the need for improved sensitivity. Clin Infect Dis. 2003 Mar 15;36(6):823-4; author reply 826-7.

Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006 Jul;34(7):1996-2003. Review.

Jones AE, Fiechtl JF, Brown MD, Ballew JJ, Kline JA. Procalcitonin test in the diagnosis of bacteremia: a meta-analysis. Ann Emerg Med. 2007 Jul;50(1):34-41. Epub 2006 Dec 11. Review.

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 Jul 15;39(2):206-17. Epub 2004 Jul 2. Review. Erratum in: Clin Infect Dis. 2005 May 1;40(9):1386-8.

Stolz D, Christ-Crain M, Gencay MM, Bingisser R, Huber PR, Müller B, Tamm M. Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection. Swiss Med Wkly. 2006 Jul 8;136(27-28):434-40.

Hirakata Y, Yanagihara K, Kurihara S, Izumikawa K, Seki M, Miyazaki Y, Kohno S. Comparison of usefulness of plasma procalcitonin and C-reactive protein measurements for estimation of severity in adults with community-acquired pneumonia. Diagn Microbiol Infect Dis. 2008 Jun;61(2):170-4. doi: 10.1016/j.diagmicrobio.2008.01.014. Epub 2008 Mar 7.

Prieto B, Llorente E, González-Pinto I, Alvarez FV. Plasma procalcitonin measured by time-resolved amplified cryptate emission (TRACE) in liver transplant patients. A prognosis marker of early infectious and non-infectious postoperative complications. Clin Chem Lab Med. 2008;46(5):660-6.

Prat C, Sancho JM, Dominguez J, Xicoy B, Gimenez M, Ferra C, Blanco S, Lacoma A, Ribera JM, Ausina V. Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia. Leuk Lymphoma. 2008 Sep;49(9):1752-61. doi: 10.1080/10428190802258956.

Charles PE, Kus E, Aho S, Prin S, Doise JM, Olsson NO, Blettery B, Quenot JP. Serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: a preliminary report. BMC Infect Dis. 2009 Apr 22;9:49. doi: 10.1186/1471-2334-9-49.

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 Jul;52(1):48-58.e2. doi: 10.1016/j.annemergmed.2008.01.003. Epub 2008 Mar 17.

Müller 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 Mar 2;7:10.

Cuquemelle E, Soulis F, Villers D, Roche-Campo F, Ara Somohano C, Fartoukh M, Kouatchet A, Mourvillier B, Dellamonica J, Picard W, Schmidt M, Boulain T, Brun-Buisson C; A/H1N1 REVA-SRLF Study Group. Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med. 2011 May;37(5):796-800. doi: 10.1007/s00134-011-2189-1. Epub 2011 Mar 3.

Schappert SM, Rechtsteiner EA. Ambulatory medical care utilization estimates for 2007. Vital Health Stat 13. 2011 Apr;(169):1-38.

Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Müller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004 Feb 21;363(9409):600-7.

Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Müller C, Huber P, Müller B, Tamm M. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007 Jan;131(1):9-19.

Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, Regez K, Schoenenberger R, Henzen C, Bregenzer T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mueller B; ProHOSP Study Group. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009 Sep 9;302(10):1059-66. doi: 10.1001/jama.2009.1297.

Long W, Deng X, Zhang Y, Lu G, Xie J, Tang J. Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia. Respirology. 2011 Jul;16(5):819-24. doi: 10.1111/j.1440-1843.2011.01978.x.


Responsible Party:	David T. Huang, MD, MPH, Associate Professor of Critcal Care and Emergency Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT02130986 History of Changes
Other Study ID Numbers:	1R01GM101197 ( U.S. NIH Grant/Contract )
Study First Received:	May 1, 2014
Last Updated:	May 31, 2017

Keywords provided by David T. Huang, MD, MPH, University of Pittsburgh:


procalcitonin (PCT) lower respiratory tract infection (LRTI) antibiotic exposure antibiotic decision making community acquired pneumonia (CAP)	chronic obstructive pulmonary disease (COPD) exacerbation acute asthma exacerbation acute bronchitis procalcitonin guideline

Additional relevant MeSH terms:


Respiratory Tract Infections Infection Respiratory Tract Diseases Anti-Bacterial Agents Antibiotics, Antitubercular	Calcitonin Anti-Infective Agents Antitubercular Agents Bone Density Conservation Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 17, 2017

Procalcitonin Antibiotic Consensus Trial (ProACT) (ProACT)