Procalcitonin to Guide Antibiotic Stop in Neurocritical Care Patients.

NCT03683693 | Unknown

• 1 other identifier: AZGS2017164
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

Antibiotic overconsumption has been considered as one of the major contributive factors of the emergence of multidrug resistant bacteria, a serious threat particularly in intensive care units. Antibiotic stewardship programs are set up to meet this problem. Shortening the duration of antimicrobial therapy seems to be one of the strongest tools of these programs. Nevertheless, the decision to stop antibiotics in a critical care patients remains often challenging in real-life practice. Procalcitonin (PCT), an inflammatory biomarker, has a promising profile and scores better than traditionally biomarkers as c-reactive protein (crp) and leucocytosis. Although two big multicenter randomised controlled trials showed a positive impact of PCT use in Intensive Care Unit (ICU), as it led to reduction of antibiotic exposure, the efficiency of this biomarker is still a point of debate. Notably the cost of PCT determination is a counterargument for its routinely use as it is a quite expensive test and its cost-benefit ratio has not been well studied. The objective of this study is to test a PCT-algorithm for stopping antibiotics in a real life setting by assessing its impact on antibiotic consumption. The investigators hypothesize that it will shorten antimicrobial courses and will decrease overconsumption, with a possible positive impact on the increase of antimicrobial resistance and with no apparent adverse outcome.

Conditions

Sepsis

Keywords

procalcitonin; antibiotic stewardship in ICU; Multidrug resistance; neurocritical care

Outcome Measures

Primary Outcomes (1)

• Antibiotic use

  We will measure the duration of the first uninterrupted antibiotic course, expressed as Days of Therapy (DOT) and as Defined Defined Daily Doses (DDD) and the Antibiotic consumption during first 28 days expressed as antibiotic free days (alive) within the first 28 days after inclusion.

  at day 28

Secondary Outcomes (9)

• ICU and mortality

  up to 6 months after inclusion

• 28-days mortality (from all causes)

  at day 28

• Hospital mortality

  up to 6 months after inclusion

• ICU and hospital length of stay

  up to 6 months after inclusion

• Duration of Mechanical ventilation

  at day 28

Study Arms (2)

Standard of Care group

NO INTERVENTION

Historical Group = Standard of Care group. Decision for stopping antibiotics taken by ICU physician: assessment on the basis of the clinical picture and traditional inflammatory biomarkers such as crp and leucocytosis

Procalcitonin group

EXPERIMENTAL

ICU physician gets on regular base PCT value, what can be used as additive tool in the decision-making for stopping antibiotics.

Diagnostic Test: Procalcitonin group

Interventions

Procalcitonin group DIAGNOSTIC_TEST

The ICU physician gets on regular base (day 0, d4, d7, d11, d15, d19, d23, d27) a PCT value and the according non-binding recommendation: PCT \< 0.5 microgram/L of 80% drop of the peak value : antibiotic stop recommended. PCT \< 0.25 microgram/L: antibiotic stop strongly recommended. The recommendation is not-binding and can be overruled by the ICU physician. The intervention is only set up for stopping antibiotics, not for initiating. PCT measurements only happens in case of still ongoing antibiotic course. In case of a second course of antibiotics, after interruption of the initial course, new PCT measurement will take place at this point followed by the continuation of the initial schedule of PCT measurement. Intervention ends 28 days after inclusion.

Procalcitonin group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients admitted to the ICU with a primary non-infectious neurological pathology:
• Traumatic Brain Injury
• Intracerebral Bleeding (pe. subarachnoid bleeding) due to aneurysm or arteriovenous malformation
• Ischemic Stroke Stroke
• Hemorrhagic stroke or other intracranial haemorrhage
• Other non-infectious neurologic condition (as hydrocephalus, status epilepticus, postoperative complication after elective neurosurgery, ...)
• AND
• requiring antibiotics within the first week (day 0 - day 6) after ICU-admission for a suspected bacterial infection

You may not qualify if:

• severe immunodeficiency and/or neutropenia: defined as (1) solid-organ transplant recipients with immunosuppressive therapy (monotherapy with corticosteroids is allowed), (2) recent chemotherapy in last 6 months, (3) hematologic malignancy with active therapy in last 2 years, (4) bone marrow transplant, (5) HIV patient with clinical complications (Pneumocystis jirovecii, Kaposi's sarcoma, lymphoma, tuberculosis, toxoplasmosis, …) or CD4 count \< 200/mm3, while neutropenia has been defined as white cell count \< 1000/ml.
• microbiologically proven infection with Pseudomonas, Acinetobacter baumannii, Lysteria or atypical pathogen as Chlamydia, Legionella or Mycoplasma; or Staphylococcal aureus bacteremia
• microbiologically proven meningitis or ventriculitis
• compartmentalised infection: pe. abscess, empyema
• microbiologically proven (co-)infection making a prolonged antibiotic course necessary, such as endocarditis, prosthetic joint infection or septic arthritis, osteomyelitis, chronic prostatitis, ...
• already \> 24h on antibiotics before ICU admission
• (expected) ICU length of stay \< 7 days
• no match available in the historical 'Standard of Care' group
• no Informed Consent obtained

Sponsors & Collaborators

• General Hospital Groeninge: lead

Study Sites (1)

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

Related Publications (11)

• Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis. 2014 Jan 9;14:13. doi: 10.1186/1471-2334-14-13.

  PMID: 24405683 BACKGROUND

• Luyt CE, Brechot N, Trouillet JL, Chastre J. Antibiotic stewardship in the intensive care unit. Crit Care. 2014 Aug 13;18(5):480. doi: 10.1186/s13054-014-0480-6.

  PMID: 25405992 BACKGROUND

• De Waele JJ, Schouten J, Dimopoulos G. Understanding antibiotic stewardship for the critically ill. Intensive Care Med. 2016 Dec;42(12):2063-2065. doi: 10.1007/s00134-015-4030-8. Epub 2015 Aug 20. No abstract available.

  PMID: 26289014 BACKGROUND

• 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.

  PMID: 20097417 BACKGROUND

• 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.

  PMID: 26947523 BACKGROUND

• Iankova I, Thompson-Leduc P, Kirson NY, Rice B, Hey J, Krause A, Schonfeld SA, DeBrase CR, Bozzette S, Schuetz P. Efficacy and Safety of Procalcitonin Guidance in Patients With Suspected or Confirmed Sepsis: A Systematic Review and Meta-Analysis. Crit Care Med. 2018 May;46(5):691-698. doi: 10.1097/CCM.0000000000002928.

  PMID: 29271844 BACKGROUND

• Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.

  PMID: 28101605 BACKGROUND

• Schuetz P, Balk R, Briel M, Kutz A, Christ-Crain M, Stolz D, Bouadma L, Wolff M, Kristoffersen KB, Wei L, Burkhardt O, Welte T, Schroeder S, Nobre V, Tamm M, Bhatnagar N, Bucher HC, Luyt CE, Chastre J, Tubach F, Mueller B, Lacey MJ, Ohsfeldt RL, Scheibling CM, Schneider JE. Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective. Clin Chem Lab Med. 2015 Mar;53(4):583-92. doi: 10.1515/cclm-2014-1015.

  PMID: 25581762 BACKGROUND

• Kourbeti IS, Vakis AF, Papadakis JA, Karabetsos DA, Bertsias G, Filippou M, Ioannou A, Neophytou C, Anastasaki M, Samonis G. Infections in traumatic brain injury patients. Clin Microbiol Infect. 2012 Apr;18(4):359-64. doi: 10.1111/j.1469-0691.2011.03625.x. Epub 2011 Aug 18.

  PMID: 21851488 BACKGROUND

• Lim HB, Smith M. Systemic complications after head injury: a clinical review. Anaesthesia. 2007 May;62(5):474-82. doi: 10.1111/j.1365-2044.2007.04998.x.

  PMID: 17448059 BACKGROUND

• Brechot N, Hekimian G, Chastre J, Luyt CE. Procalcitonin to guide antibiotic therapy in the ICU. Int J Antimicrob Agents. 2015 Dec;46 Suppl 1:S19-24. doi: 10.1016/j.ijantimicag.2015.10.012. Epub 2015 Nov 1.

  PMID: 26607343 BACKGROUND

Related Links

• World Health Organisation (WHO) Collaborating Centre for Drug Statistics Methodology 2015

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stoffel Lamote, MD

  AZ Groeninge

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stoffel Lamote, MD

CONTACT

3256633055; stoffel.lamote@azgroeninge.be

Wouter De Corte, MD, PhD

CONTACT

3256633047; wouter.decorte@azgroeninge.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Stoffel Lamote, MD

Model Details: Matched cohort: historical standard of care group (patients from the period January 2016 - April 2018) versus interventional group (patients from May 2018 on)

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: September 25, 2018
• Study Start: May 7, 2018
• Primary Completion: May 1, 2020
• Study Completion: September 1, 2020
• Last Updated: September 25, 2018

Record last verified: 2018-09

Locations

BE (1)