Procalcitonin Antibiotic Consensus Trial (ProACT)

Lower Respiratory Tract Infection (LRTI) Clinical Trial

— ProACT  

Official title:

Procalcitonin Antibiotic Consensus Trial (ProACT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02130986
• Other study ID #: 1R01GM101197
• Secondary ID: 1R01GM101197
• Status: Completed
• Phase: N/A
• Start date: November 3, 2014
• Est. completion date: July 21, 2017

Study information

• Verified date: January 2019
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1664
• Est. completion date: July 21, 2017
• Est. primary completion date: July 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lower Respiratory Tract Infection (LRTI)
• Respiratory Tract Infections

Intervention

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.
• Results of procalcitonin (PCT) level to treating clinician
In the ED, we will quickly (<1 hour goal) provide clinicians the procalcitonin result.
• 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.
• Telephone Visit
We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30

Locations

Country	Name	City	State
United States	University of Maryland/Baltimore	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Ohio State University, College of Medicine	Columbus	Ohio
United States	Wayne State University/Detroit Receiving Hospital	Detroit	Michigan
United States	Essentia Institute of Rural Health	Duluth	Minnesota
United States	Penn State Hershey College of Medicine; Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Norwalk Hospital	Norwalk	Connecticut
United States	University of California at Irvine Medical Center	Orange	California
United States	Maricopa Medical Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pittsburgh	BioMérieux, National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

References & Publications (20)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Antibiotic Exposure Days	Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30.	30 days
Primary	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	Antibiotic Prescription in Emergency Department(ED)	Antibiotic prescription in the ED includes post-randomization receipt of antibiotics in ED and provision of an antibiotic prescription for patients at the time of discharge from the ED.	While in the ED or before ED discharge (majority patients < 1 day)