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The Procalcitonin And Survival Study (PASS) - a randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients.

ABSTRACT: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients.Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients.For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).

SUBMITTER: Jensen JU

PROVIDER: S-EPMC2491622 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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The Procalcitonin And Survival Study (PASS) - a randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients.

Jensen Jens-Ulrik JU Lundgren Bettina B Hein Lars L Mohr Thomas T Petersen Pernille L PL Andersen Lasse H LH Lauritsen Anne O AO Hougaard Sine S Mantoni Teit T Bømler Bonnie B Thornberg Klaus J KJ Thormar Katrin K Løken Jesper J Steensen Morten M Carl Peder P Petersen J Asger JA Tousi Hamid H Søe-Jensen Peter P Bestle Morten M Hestad Søren S Andersen Mads H MH Fjeldborg Paul P Larsen Kim M KM Rossau Charlotte C Thomsen Carsten B CB Ostergaard Christian C Kjaer Jesper J Grarup Jesper J Lundgren Jens D JD

BMC infectious diseases 20080713

<h4>Background</h4>Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unac ...[more]

PMID: 18620598

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Project description: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.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%).(1) ICU-patients aged ?18 years and (2) receiving antibiotics for a presumed or proven infection and (3) signed informed consent.(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.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 number at www.clinicaltrials.gov: Id. Nr. NCT01139489, at www.trialregister.nl: Id.nr. NTR1861.

Project description:Objective:In children many antiepileptic drugs (AEDs) are prescribed off-label due to a lack of well-designed randomized controlled trials (RCTs). We conducted a multicenter RCT in the Netherlands to compare levetiracetam and valproic acid as monotherapy in children with newly diagnosed epilepsy. After 2 years, we had to stop this investigator-initiated trial prematurely because the inclusion rate was too low. We analyzed the reasons for this failure, assessed the various issues involved in performing RCTs in children, and now give recommendations for future studies. Methods:A questionnaire was completed by all investigators involved in the study. It included questions about the motivation to participate and the perceived reasons for recruitment failure. We also studied literature about financial, logistic, legal, and ethical aspects of RCTs in children. Results:Main reasons for recruitment failure were overestimation of the number of eligible AED-naive children referred by general pediatricians; personal preferences of investigators for specific antiepileptic drugs; and the extensive administrative load due to extra regulations and guidelines for children. Fundraising for investigator-initiated trials is difficult and the majority of RCTs concerning AEDs are sponsored by pharmaceutical companies. Involving children requires balancing between protection and participation; the randomization procedure and obtaining informed consent are complex for both children and parents. Significance:Performing RCTs with AEDs in children is important but complicated by logistic, regulatory, legal, and ethical restrictions. Based on our recent experience, our advice to colleagues who are planning a similar trial would be to perform a feasibility pilot study; to set up intensive collaboration with referring pediatricians; to arrange support of a clinical trials unit and a local research nurse during the complete trial period; and to incorporate the possibility of extending the recruitment period. Major investments, both financially from governmental organizations and in time, are imperative for independent RCTs in children.

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