Procalcitonin Level to Discontinue Antibiotics on ICU Patients With no Obvious Site of Infection

Sepsis Clinical Trial

Official title:

ProBac - Use of Procalcitonin Level as Part of a Decision Tree to Discontinue Antibiotics When Started Empirically in the ICU in Hemodynamically Stable Patients With no Site of Infection Identified

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00407147
• Other study ID #: ProBac
• Status: Terminated
• Phase: Phase 4
• First received: November 29, 2006
• Last updated: January 16, 2012
• Start date: July 2008
• Est. completion date: June 2009

Study information

• Verified date: January 2012
• Source: Brahms AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardGermany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test whether a U.S. Food and Drug Administration (FDA) approved laboratory test (PCT Kryptor) can help doctors make better decisions on the need for antibiotic therapy in ICU patients with suspected infections.

Description:

The study is undertaken as prospective, randomized, controlled, multicenter trial. The study population, ICU patients with empiric antibiotic treatment due to suspected but unproven infection, is randomly assigned to either a Standard Care Group or a Procalcitonin (PCT) Guided Group. In the standard care group, antibiotic treatment would be based totally on clinical decision making with "traditional thought processes" (i.e., cultures, response to antibiotics, risk of untreated infection, other laboratory findings, etc.). The PCT guided group will use the same "traditional thought processes" and in addition the physician will be given access to a PCT value for Day 1 and Day 4 along with the recommended thresholds for likelihood of infection. In conjunction with other laboratory findings and clinical assessments the threshold of PCT is used to continue or discontinue empiric antibiotic treatment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Suspected infection (no clear-cut source of infection) as defined by the treating physician

• Empiric antibiotic treatment

• No clear-cut source of infection by clinical or microbiological criteria

• ICU patient

• Informed consent

Exclusion Criteria:

• Age <18 years

• Pregnancy

• Hemodynamic instability defined as persistent hypotension, need for on-going aggressive resuscitation and/or vasopressor support to maintain an adequate mean arterial blood pressure

• Need for antibiotic prophylaxis

• Patient withdrawn from empiric antibiotic treatment before Day 4

• Severely immuno-compromised patient (liver cirrhosis (Child-Pugh class C), immunosuppressive drugs after transplantation, neutropenia (absolute neutrophil count <1000 counts/L), CD-4 count less than 200)

• Patient with suspected bacterial or fungal endocarditis

• Patient with suspected meningitis

• Cardiopulmonary bypass within the last 7 days1)

• Major surgery within the last 7 days (surgery that induces a major inflammatory response such as heart or aortic surgery or major abdominal surgery (i.e. duodenopancreatectomy) or any surgery requiring massive blood transfusion.)

• Multiple trauma within the last 7 days

• Cardiopulmonary resuscitation (CPR) within the last 7 days

• Burns >20% body surface area

• Patient in terminal status referred for palliative care

• Patient with advanced directives or Do Not Resuscitate (DNR) orders

• Patient who is already enrolled in another therapeutic clinical study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Infection
• Bacterial Infections
• Communicable Diseases
• Infection
• Sepsis

Intervention

Device:
• Procalcitonin assay - B.R.A.H.M.S PCT sensitive Kryptor
antibiotic treatment based on clinical decision making with "traditional thought processes" used in both groups. In addition the physician will be given access to Procalcitonin values with recommended thresholds for likelihood of infection.

Locations

Country	Name	City	State
United States	Cooper University Hospital	Camden	New Jersey
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Saint Louis University - medical intensive care unit	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Brahms AG

Country where clinical trial is conducted

United States, 

References & Publications (8)

Bergmans DC, Bonten MJ, Gaillard CA, van Tiel FH, van der Geest S, de Leeuw PW, Stobberingh EE. Indications for antibiotic use in ICU patients: a one-year prospective surveillance. J Antimicrob Chemother. 1997 Apr;39(4):527-35. — 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

Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med. 2003 Dec;31(12):2742-51. — View Citation

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818-29. — View Citation

Meisner M, Tschaikowsky K, Palmaers T, Schmidt J. Comparison of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS. Crit Care. 1999;3(1):45-50. — View Citation

Rau B, Steinbach G, Gansauge F, Mayer JM, Grünert A, Beger HG. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis. Gut. 1997 Dec;41(6):832-40. — View Citation

Røder BL, Nielsen SL, Magnussen P, Engquist A, Frimodt-Møller N. Antibiotic usage in an intensive care unit in a Danish university hospital. J Antimicrob Chemother. 1993 Oct;32(4):633-42. — View Citation

Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH, Wolff M, Spencer RC, Hemmer M. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. 1995 Aug 23-30;274(8):639-44. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days on antibiotics beginning with day 4 until the first day without antibiotics (up to max. 28 days follow up)		28 days	No
Secondary	Days on antibiotics during ICU stay		up to 28 days	No
Secondary	Sepsis classification		up to 28 days	No
Secondary	SOFA score (modified)		up to 28 days	No
Secondary	ICU or hospital mortality up to 28 days		up to 28 days	No
Secondary	Frequency of infections		up to 28 days	No
Secondary	ICU and hospital length of stay		up to 28 days	No