Procalcitonin Antibiotic Consensus Trial (ProACT)

NCT02130986 | Completed Results DMC

• 1 other identifier: 1R01GM101197
• Study Type: interventional
• Target: 1,664
• Locations: 1 country
• Sites: 13

Brief Summary

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).

Conditions

Lower Respiratory Tract Infection (LRTI)

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Total Antibiotic Exposure Days

  Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30.

  30 days

• Number of Participants With Any Adverse Outcome

  Primary Safety Outcome - Combined endpoint of adverse outcomes (death, endotracheal intubation, vasopressors, renal failure, lung abscess/empyema, pneumonia in non-CAP patient, and hospital readmissions) that could be attributable to withholding antibiotics in lower respiratory tract infection (LRTI). Number is based on the number of participants that experienced any adverse outcome.

  30 days

Secondary Outcomes (1)

• Antibiotic Prescription in Emergency Department(ED)

  While in the ED or before ED discharge (majority patients < 1 day)

Study Arms (2)

Procalcitonin (PCT) group

EXPERIMENTAL

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; Other: Results of procalcitonin (PCT) level to treating clinician; Other: Provide procalcitonin guideline to treating clinician; Other: Telephone Visit

Usual Care group

ACTIVE COMPARATOR

Telephone Visit at Day 15 and Day 30

Other: Telephone Visit

Interventions

Procalcitonin level OTHER

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.

Also known as: PCT level

Procalcitonin (PCT) group

Results of procalcitonin (PCT) level to treating clinician OTHER

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

Procalcitonin (PCT) group

Provide procalcitonin guideline to treating clinician OTHER

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) 1. 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. 2. 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.

Procalcitonin (PCT) group

Telephone Visit OTHER

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

Procalcitonin (PCT) group; Usual Care group

Eligibility Criteria

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

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of General Medical Sciences (NIGMS): collaborator
• BioMérieux: collaborator

Study Sites (13)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Maricopa Medical Center

Phoenix, Arizona, 85008, United States

Location

University of California at Irvine Medical Center

Orange, California, 92868, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

University of Maryland/Baltimore

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Essentia Institute of Rural Health

Duluth, Minnesota, 55805, United States

Location

The Ohio State University, College of Medicine

Columbus, Ohio, 43210, United States

Location

Penn State Hershey College of Medicine; Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (23)

• Meisner M. Biomarkers of sepsis: clinically useful? Curr Opin Crit Care. 2005 Oct;11(5):473-80. doi: 10.1097/01.ccx.0000176694.92883.ce.

  PMID: 16175035 BACKGROUND

• Schuetz P, Christ-Crain M, Muller 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: 10.4414/smw.2009.12584.

  PMID: 19529989 BACKGROUND

• 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 Jan;86(1):396-404. doi: 10.1210/jcem.86.1.7089.

  PMID: 11232031 BACKGROUND

• 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. doi: 10.1086/368088. No abstract available.

  PMID: 12627371 BACKGROUND

• 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. doi: 10.1097/01.CCM.0000226413.54364.36.

  PMID: 16715031 BACKGROUND

• 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. doi: 10.1016/j.annemergmed.2006.10.020. Epub 2006 Dec 11.

  PMID: 17161501 BACKGROUND

• 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. doi: 10.1086/421997. Epub 2004 Jul 2.

  PMID: 15307030 BACKGROUND

• Stolz D, Christ-Crain M, Gencay MM, Bingisser R, Huber PR, Muller 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. doi: 10.4414/smw.2006.11271.

  PMID: 16862463 BACKGROUND

• 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.

  PMID: 18329217 BACKGROUND

• Prieto B, Llorente E, Gonzalez-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. doi: 10.1515/cclm.2008.123.

  PMID: 18839468 BACKGROUND

• 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.

  PMID: 18661397 BACKGROUND

• 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.

  PMID: 19386110 BACKGROUND

• 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.

  PMID: 18342993 BACKGROUND

• 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 Mar 2;7:10. doi: 10.1186/1471-2334-7-10.

  PMID: 17335562 BACKGROUND

• 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.

  PMID: 21369807 BACKGROUND

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

  PMID: 21614897 BACKGROUND

• 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 Feb 21;363(9409):600-7. doi: 10.1016/S0140-6736(04)15591-8.

  PMID: 14987884 BACKGROUND

• 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 Jan;131(1):9-19. doi: 10.1378/chest.06-1500.

  PMID: 17218551 BACKGROUND

• 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.

  PMID: 19738090 BACKGROUND

• 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.

  PMID: 21507143 BACKGROUND

• Malley BE, Yabes JG, Gimbel E, Chang CH, Yealy DM, Fine MJ, Angus DC, Huang DT; ProACT Investigators. Impact of adherence to procalcitonin antibiotic prescribing guideline recommendations for low procalcitonin levels on antibiotic use. BMC Infect Dis. 2023 Jan 19;23(1):30. doi: 10.1186/s12879-022-07923-0.

  PMID: 36658543 DERIVED

• Huang DT, Yealy DM, Filbin MR, Brown AM, Chang CH, Doi Y, Donnino MW, Fine J, Fine MJ, Fischer MA, Holst JM, Hou PC, Kellum JA, Khan F, Kurz MC, Lotfipour S, LoVecchio F, Peck-Palmer OM, Pike F, Prunty H, Sherwin RL, Southerland L, Terndrup T, Weissfeld LA, Yabes J, Angus DC; ProACT Investigators. Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection. N Engl J Med. 2018 Jul 19;379(3):236-249. doi: 10.1056/NEJMoa1802670. Epub 2018 May 20.

  PMID: 29781385 DERIVED

• Huang DT, Angus DC, Chang CH, Doi Y, Fine MJ, Kellum JA, Peck-Palmer OM, Pike F, Weissfeld LA, Yabes J, Yealy DM; ProACT Investigators. Design and rationale of the Procalcitonin Antibiotic Consensus Trial (ProACT), a multicenter randomized trial of procalcitonin antibiotic guidance in lower respiratory tract infection. BMC Emerg Med. 2017 Aug 29;17(1):25. doi: 10.1186/s12873-017-0138-1.

  PMID: 28851296 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia; Pulmonary Disease, Chronic Obstructive; Bronchitis

Interventions

Procalcitonin

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Calcitonin; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Protein Precursors; Proteins

Results Point of Contact

• Title: David T Huang, MD, MPH, Associate Professor
• Organization: University of Pittsburgh

huangdt@upmc.edu

412-647-6818

Study Officials

• David T Huang, MD MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Critcal Care and Emergency Medicine

Study Record Dates

• First Submitted: May 1, 2014
• First Posted: May 6, 2014
• Study Start: November 3, 2014
• Primary Completion: July 21, 2017
• Study Completion: July 21, 2017
• Last Updated: January 15, 2019
• Results First Posted: January 15, 2019

Record last verified: 2019-01

Locations

US (13)