Clinical trial NCT00407147: Procalcitonin Level to Discontinue Antibiotics on ICU Patients With no Obvious Site of Infection
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Infection
Bacterial Infection
Sepsis
Keywords: bacterial infection
empiric antibiotic treatment
duration antibiotic treatment
reduce antibiotic treatment
procalcitonin
PCT Kryptor
sepsis
Intensive Care Unit
antibiotic treatment
Lead sponsor: Brahms AG
Sponsor class: INDUSTRY
First posted: 2006-12-04
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Days on antibiotics beginning with day 4 until the first day without antibiotics (up to max. 28 days follow up)
timeFrame: 28 days
Secondary outcomes:
measure: Days on antibiotics during ICU stay
timeFrame: up to 28 days
measure: Sepsis classification
timeFrame: up to 28 days
measure: SOFA score (modified)
timeFrame: up to 28 days
measure: ICU or hospital mortality up to 28 days
timeFrame: up to 28 days
measure: Frequency of infections
timeFrame: up to 28 days
measure: ICU and hospital length of stay
timeFrame: up to 28 days
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Saint Louis University - medical intensive care unit
state: Missouri
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
affiliation: The Cooper Health System
name: Phil Dellinger, M.D.
role: STUDY_CHAIR
References:
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.
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. doi: 10.1097/01.CCM.0000098031.24329.10.
citation: 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.
citation: Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert 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. doi: 10.1136/gut.41.6.832.
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. doi: 10.1186/cc306.
citation: 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. doi: 10.1093/jac/39.4.527.
citation: Roder BL, Nielsen SL, Magnussen P, Engquist A, Frimodt-Moller N. Antibiotic usage in an intensive care unit in a Danish university hospital. J Antimicrob Chemother. 1993 Oct;32(4):633-42. doi: 10.1093/jac/32.4.633.
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.