Safety and Efficacy of Procalcitonin Guided Antibiotic Therapy in Adult Intensive Care Units (ICU's) (SAPS)

Stop Antibiotics on Procalcitonin Guidance Study

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).

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Severe Sepsis
• Intervention / Treatment: Other: procalcitonin-guidance

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.

• Study Type: Interventional
• Enrollment (Actual): 1575
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: procalcitonin-guidance; A daily advise to continue or stop antibiotics based on the measurement of the biomarker procalcitonin	Other: procalcitonin-guidance; If procalcitonin levels decrease to predefined levels, antibiotic therapy will be discontinued.; Other Names: PCT
No Intervention: standard-of-care; standard-of-care treatment of ICU infections based upon consensus guidelines and expert opinion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality	1 year
Mortality	28 days
Consumption of antibiotics expressed as the Defined Daily Dosage and duration of antibiotic therapy expressed in days of therapy.	Between day 1 and D28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of ICU stay		Between D1 and D28
Acquisition costs of antibiotics	Expressed in euro's	Between D1-D28
Acquisition costs of procalcitonin	Expressed in euro's	Between D1-D28

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: UMC Utrecht; Dijklander Ziekenhuis; Medical Center Haaglanden; Elisabeth-TweeSteden Ziekenhuis; University of Groningen; Diakonessenhuis, Utrecht; Isala; Canisius-Wilhelmina Hospital; Martini Hospital Groningen; Medisch Spectrum Twente; Atrium Medical Center; Slotervaart Hospital; Bronovo Hospital; St. Lucas Andreas Ziekenhuis Hospital
• Investigators: Principal Investigator: Evelien de Jong, MSc, Amsterdam Umc, Location Vumc

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: March 8, 2010
• First Submitted That Met QC Criteria: June 7, 2010
• First Posted (Estimate): June 8, 2010

Study Record Updates

• Last Update Posted (Estimate): January 6, 2016
• Last Update Submitted That Met QC Criteria: January 5, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: biomarker; infections; Procalcitonin; sepsis; antibiotics; antibiotic therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: VU University medical center; NTR1861 (Other Identifier: Nederlands Trial Register)