Clinical trial NCT01085994: Procalcitonin Monitoring May Decrease Antibiotic Use in the Intensive Care Unit
Official title: Procalcitonin-guided Algorithms of Antibiotic Stewardship in the Intensive Care Unit: Systematic Review and Meta-analysis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sepsis
Keywords: antibiotics
resistance
bio-marker
procalcitonin
algorithm
critically ill
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2010-03-12
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Sampling method: PROBABILITY_SAMPLE
Study population: We will systematically search PubMed, Scopus and the Cochrane Central Register of Controlled Trials to identify relevant randomized controlled trials by using the following search terms: procalcitonin AND ("critically ill" OR "intensive care" OR "critical care"). The reference lists of the initially retrieved articles will also be reviewed. Abstracts of conference proceedings will not be sought because they commonly present data that differ from the full publications. Finally, the corresponding authors of each one of the included studies will be contacted by e-mail for additional information and clarifications if needed.

Brief summary: Sepsis is common and is associated with significant mortality, morbidity and health-care costs. Unfortunately, its diagnosis is not straightforward because its signs and symptoms are neither specific nor sensitive; in addition, microbiological cultures lack specificity, sensitivity and are plagued by high turn-around times. Because the delay in the institution of antimicrobial therapy may be deleterious, broad-spectrum antibiotics are widely used in ICU-patients, even when they are not needed. Procalcitonin may not be the long sought for bio-marker to establish the diagnosis of sepsis but may help decrease the duration of the administered antibiotic courses once they are started.

Detailed description: Recently, a number of studies have shown the utility of procalcitonin (PCT) measurements in reducing the duration of antibiotic treatment in patients with respiratory tract infections presenting to the primary care setting or the emergency department. However, it remains unclear if a similar strategy can be effectively and safely implemented in the critical care setting. We attempt to address the controversy on this issue, by collecting, analyzing and interpreting the currently available relevant evidence. To this end, a systematic review and meta-analysis of the randomized controlled trials reporting on the outcomes of critically ill septic patients managed with or without a procalcitonin-based algorithm will be performed.

Eligibility criteria: Inclusion Criteria:

* Randomized controlled trials (RCTs) that report on the outcomes of critically ill patients managed with a procalcitonin-guided algorithm versus routine practice.
* Participants of any age with proven or suspected sepsis will be considered. - As routine practice, the investigators will consider the institution and discontinuation of antibiotics by the attending physicians with the aid of clinical signs, symptoms, microbiological data, well established laboratory parameters (i.e., white blood cell count) and widely accepted guidelines but without the knowledge of PCT values. The investigators will set no limitations regarding the time, country or language of publications. The investigators will search for trials conducted in critically ill neonates and children.

Exclusion Criteria:

* The investigators will exclude studies that are not RCTs and studies performed outside the ICU, namely in the primary care setting, the emergency department or the clinic.

Primary outcomes:
measure: Duration of antibiotic treatment for the first episode of infection
measure: Total duration of antibiotic therapy
measure: Antibiotic-free days at 28 days after study enrollment
Secondary outcomes:
measure: 28-day mortality
measure: In-hospital mortality
measure: Length of ICU stay
measure: Length of hospital stay
measure: Days free of mechanical ventilation at 28 days after study enrollment
measure: Rates of relapsed/persistent infection
measure: Rate of superinfection
measure: Financial cost of implementing a procalcitonin-based algorithm: purchase of the laboratory equipment/reagents, cost of the administered antibiotics, charges for hospital stay etc
Other outcomes:
Locations:
city: Athens
country: Greece
facility: University of Athens - Medical School
Study officials:
affiliation: University of Athens Medical School
name: Petros Kopterides, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Regnier B, Brun-Buisson C, Chastre J, Wolff M; PRORATA trial group. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010 Feb 6;375(9713):463-74. doi: 10.1016/S0140-6736(09)61879-1. Epub 2010 Jan 25.
citation: Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009 Aug 18;151(4):264-9, W64. doi: 10.7326/0003-4819-151-4-200908180-00135. Epub 2009 Jul 20. No abstract available.
citation: Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med. 2010 Nov;38(11):2229-41. doi: 10.1097/CCM.0b013e3181f17bf9.