Clinical trial NCT01139489: Safety and Efficacy of Procalcitonin Guided Antibiotic Therapy in Adult Intensive Care Units (ICU's)
Official title: Stop Antibiotics on Procalcitonin Guidance Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Severe Sepsis
Septic Shock
Keywords: Procalcitonin
antibiotic therapy
antibiotics
sepsis
infections
biomarker
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: Elisabeth-TweeSteden Ziekenhuis
name: Diakonessenhuis, Utrecht
name: Isala
name: Atrium Medical Center
name: Dijklander Ziekenhuis
name: Bronovo Hospital
name: Medical Center Haaglanden
name: Slotervaart Hospital
name: University of Groningen
name: Martini Hospital Groningen
name: Canisius-Wilhelmina Hospital
name: Medisch Spectrum Twente
name: St. Lucas Andreas Ziekenhuis Hospital
First posted: 2010-06-08
Enrollment: 1575
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: This is a randomized controlled trial comparing standard-of-care therapy of infections in critically ill patients with a procalcitonin-guided approach evaluating efficacy (antibiotics consumption) and safety (mortality).

Detailed description: Antibiotics are prescribed widely in intensive care units and are linked with high costs and the occurence of antimicrobial (multi)resistance. The optimal duration of antibiotic treatment is poorly known and often based on consensus guidelines.

SAPS is a multicenter, prospective, randomized, controlled open-label trial evaluating the equivalence/efficacy and safety of procalcitonin-guided treatment of infections in ICU patients versus a standard-of-care approach.

All patients that are admitted to the ICU and for whom systemic antibiotics are prescribed for presumed or proven bacterial infections are eligible for this trial. Patients will be randomized and stratified according to clinical diagnosis of severe sepsis and septic shock. Any patient over the age of 18, admitted to the ICU and receiving antibiotics for an assumed infection can be enrolled into this trial. Informed consent has to be obtained in writing from the patient of his/her relatives prior to inclusion. In the intervention group daily procalcitonin levels be performed and will generate a non-binding stopping advice when predefined stopping-rules have been reached. The ultimate decision to stop antibiotics will be at the discretion of the physician in both groups.

Eligibility criteria: Inclusion Criteria:

* Age over 18 years old
* receiving antibiotics for no more than 24 hours for an assumed or proven infection
* Informed consent

Exclusion Criteria:

* Failure to obtain written consent to participate
* Patients receiving prolonged antibiotic therapies (\> 3 weeks, e.g. endocarditis, cerebral/hepatic abscess)
* Patients with severe infections due to viruses or parasites (e.g. Dengue, Toxoplasma gondii, Plasmodium spp.)
* Patients infected with Mycobacterium tuberculosis
* Patients entering the ICU for post-operative observation and/or on antibiotic prophylaxis with an estimated length of stay less then 24 hrs.
* Patients suffering from cystic fibrosis
* Severely immunocompromised patients such as patients with HIV and with a CD4 count of less than 200 cells/mm, neutropenic patients (\<500 neutrophils per mL) or patients with solid organ transplantation
* Moribund patients

Primary outcomes:
measure: Mortality
timeFrame: 28 days
measure: Consumption of antibiotics expressed as the Defined Daily Dosage and duration of antibiotic therapy expressed in days of therapy.
timeFrame: Between day 1 and D28
measure: Mortality
timeFrame: 1 year
Secondary outcomes:
measure: Length of ICU stay
timeFrame: Between D1 and D28
measure: Acquisition costs of antibiotics
timeFrame: Between D1-D28
measure: Acquisition costs of procalcitonin
timeFrame: Between D1-D28
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University medical center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Evelien de Jong, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE, Loef BG, Dormans T, van Melsen GC, Kluiters YC, Kemperman H, van den Elsen MJ, Schouten JA, Streefkerk JO, Krabbe HG, Kieft H, Kluge GH, van Dam VC, van Pelt J, Bormans L, Otten MB, Reidinga AC, Endeman H, Twisk JW, van de Garde EMW, de Smet AMGA, Kesecioglu J, Girbes AR, Nijsten MW, de Lange DW. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016 Jul;16(7):819-827. doi: 10.1016/S1473-3099(16)00053-0. Epub 2016 Mar 2.
citation: Assink-de Jong E, de Lange DW, van Oers JA, Nijsten MW, Twisk JW, Beishuizen A. Stop Antibiotics on guidance of Procalcitonin Study (SAPS): a randomised prospective multicenter investigator-initiated trial to analyse whether daily measurements of procalcitonin versus a standard-of-care approach can safely shorten antibiotic duration in intensive care unit patients--calculated sample size: 1816 patients. BMC Infect Dis. 2013 Apr 16;13:178. doi: 10.1186/1471-2334-13-178.