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Open Access Highly Accessed Study protocol

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

Evelien Assink-de Jong1, Dylan W de Lange2, Jos A van Oers3, Maarten W Nijsten4, Jos W Twisk5 and Albertus Beishuizen16*

Author Affiliations

1 Department of Intensive Care, VU University Medical Center, Boelelaan 1117, Amsterdam, 1081 HV, Netherlands

2 Department of Intensive Care and Emergency Medicine, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands

3 Department of Intensive Care, St. Elisabeth Hospital Tilburg, Hilvarenbeekseweg 60, Tilburg, 5022 GC, Netherlands

4 Department of Critical Care, University Medical Center Groningen, Hanzeplein 1, Groningen, 9700 RB, Netherlands

5 Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Boelelaan 1117, Amsterdam, 1081 HV, Netherlands

6 Department of Intensive Care, Medisch Spectrum Twente, Haaksbergerstraat 55, Enschede, 7513 ER, Netherlands

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BMC Infectious Diseases 2013, 13:178  doi:10.1186/1471-2334-13-178

Published: 16 April 2013

Abstract

Background

Unnecessary long-term use of broad-spectrum antibiotics is linked to the emergence and selection of resistant bacteria, prolonged hospitalisation and increased costs. Several clinical trials indicate that the biomarker procalcitonin (PCT) can guide antibiotic therapy. Some of these trials have shown a promising reduction in the number of antibiotic prescriptions, duration of antibiotic therapy and even length of stay in the ICU, although their size and selection criteria limit their external validity. The objectives of the Stop Antibiotics on guidance of Procalcitonin Study (SAPS) are to evaluate whether daily PCT can improve “real-life” antibiotic use in Dutch ICU’s by reduction of the duration of antibiotic treatment without an increase of recurrent infections and mortality.

Methods/Design

Multicenter randomised controlled intervention trial. Powered for superiority of the primary efficacy endpoint and non-inferiority on the primary safety endpoints (non-inferiority margin is set on 8%).

Inclusion criteria: (1) ICU-patients aged ≥18 years and (2) receiving antibiotics for a presumed or proven infection and (3) signed informed consent. Exclusion criteria: (1) patients who require prolonged antibiotic therapy, (2) suffer from Mycobacterium tuberculosis, (3) cystic fibrosis, (4) viral or parasitic infections and (5) those that are severely immunocompromised or (6) moribund.

The intervention consists solely of an advice to discontinue antibiotic treatment in case PCT has decreased by more than 80% of its peak level (relative stopping threshold) or decrease below a value of 0.5 ng/ml (absolute stopping threshold).

The study hypothesis is that PCT-guided therapy is non-inferior to standard care based on implemented guidelines and local expertise, whilst reducing antibiotic usage. Computerised 1:1 randomisation will allocate 908 patients per arm. Arm 1: standard of care. Arm 2: procalcitonin-guided therapy. The primary efficacy endpoint is consumption of antibiotics expressed as the defined daily dosage and duration of antibiotic therapy expressed in days of therapy. This trial is designed to shorten antibiotics safely, therefore the primary safety endpoint is mortality measured at 28 day and 1 year.

Discussion

This will be the largest procalcitonin-guided antibiotic intervention trial in ICU setting thus far. Currently 1600 of the planned 1816 patients are randomised (November 2012). The first interim analysis has passed without any safety or futility issues.

Trial registration

Trial registration number at http://www.clinicaltrials.gov webcite: Id. Nr. NCT01139489 , at http://www.trialregister.nl webcite: Id.nr. NTR1861.

Keywords:
Antibiotics; Antibiotic duration; Biomarker; Critical illness; C-reactive protein; Defined daily dosage; Intensive care unit; Procalcitonin; Sepsis; Septic shock