SepsisNCT03683693
Procalcitonin to Guide Antibiotic Stop in Neurocritical Care Patients.
A study testing Procalcitonin group in people with Sepsis, run by General Hospital Groeninge at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Procalcitonin group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 1 siteBelgium
- Study dates
- 7 May 2018to Sep 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- (expected) ICU length of stay < 7 days
- no match available in the historical 'Standard of Care' group
- no Informed Consent obtained
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
AZ Groeninge
Kortrijk, 8500
Stoffel Lamote, MD
About this study
Official title: Procalcitonin to Guide Antibiotic Stop in Neurocritical Care Patients. An Interventional Matched-cohort Study.
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.
Read the detailed description
This is a single center, before-after, matched cohort study in a ICU of a non-university hospital. It puts the focus on neurocritical care patients as they are prone to infectious complications and these cases are often less straightforward in terms of diagnosis and management. The investigators hypothesise that such an algorithm, in addition to clinical judgement of the ICU physician, will reduce the duration of antibiotic treatment and the overall antibiotic use, could reduce selective pressure, without increase of mortality or recurrent infections.
All patients admitted to ICU with a primary non-infectious neurologic pathology will be screened for eligibility. Eligible patients can be enrolled if they meet all the inclusion criteria, there are no exclusion criteria, a matched control is available and an informed consent has provided by the patient or his or her legal representative. Patients included in the intervention group will be 1:1 matched with a patient out of the historical control group. Therefore, three fixed and two variable criteria for matching will be used. The fixed ones are: 1. pathology (traumatic brain injury; intracerebral/subarachnoid hemorrhage due to cerebral aneurysm or arteriovenous malformation; ischemic stroke; hemorrhagic stroke or other intracranial hemorrhage from; and the whether or not need for intervention (none, endovascular or neurosurgical intervention) . 2. need for mechanical ventilation within the first 12 hours after admission and 3. Glasgow coma scale (GCS) < 8 versus ≥ 8 at ICU admission or before starting sedation or anesthesia.
The two variable criteria are age (with a range of plus or minus 10 years) and the Acute Physiology and Chronic Health Evaluation (APACHE)-II score (with a range of plus or minus 15 points).
Matching will be manually, blinded for the outcome. A control group has been composed by analysing retrospectively patients admitted to our ICU from January 2016 on.
In the intervention group, doctors are additionally provided with PCT levels on regular base and with a non-binding advice on continuation or discontinuation of antibiotic therapy by electronic patient data management system feedback and by the involved microbiologist. The first PCT value will be used just as base-line, without any therapeutic consequence. Measurements will be repeated every 3-4 days, the last one is scheduled at day 27.
Patients in both groups are followed until hospital discharge, allowing assesment of hospital length of stay, hospital mortality and prevalence of multidrug resistance during hospitalisation.
Following data were collected at initiation of the trial : age, sex, BMI, pre-existing comorbidities including presence of known multidrug resistant bacteria before ICU admission, previous location before admission, reason for admission, GCS at admission to ICU, intervention, reason for antibiotic start, day of ICU admission at starting point of the study, APACHE II, the presence and type of organ dysfunction using the sequential organ-failure assessment (SOFA) score and use of mechanical ventilation.
Subsequently, following parameters will be recorded during ICU stay: SOFA score and type of organ or system failure at every PCT measurement, daily need for mechanical ventilation, source of infection when known and results of microbiological cultures. Additionally, the inflammatory biomarkers crp and leucocytosis as well as maximum temperature will be daily registered.
At the end of follow-up, every suspected infectious episode will be sorted by the investigator into four groups: 1. microbiologically documented infection (presence of a clinical and/or radiological infectious focus and pathogen identification); 2. clinically documented infection (presence of a clinical and/or radiological infectious focus, without causative pathogen identification); 3. absence of infection (absence of a clinical or radiological infectious focus) 4. possible infection (all other situations).
Data management will be performed by the investigators or research nurses. Patient's anonymity will be maintained by identifying enrolled patients of both groups with a trial identification number. The list containing the subjects name and allocation numbers are kept in strict confidence. Electronical clinical research files (CRF) or other subject related data will be protected by a password and will be put on a secured server within the hospital. Similarly, written papers (including CRF on paper) containing privacy sensitive information will be kept behind locked doors.
For the power analysis, the ICU databank has been queried, analysing the antibiotic duration of the first, uninterrupted antibiotic course of 74 patients who stayed at least 10 days in ICU in 2016 and got empirical and/or directed antibiotic therapy. A lognormal distribution with a peak value at 11.78 days has been found. After log-transformation, a mean of 2.466 with standard deviation of 0.433 was found.
The investigators aim for 20% antibiotic reduction, supported by the results of the PRORATA and the SAPS trial. This goal is ambitious, but is not unrealistic, taking into account that the study population group is traditionally characterized by high figures of antibiotic consumption. Based on these assumptions, a number of 60 patients in both groups is required for obtaining a power of 80%. This number has been increased with 10%, anticipating for patients who will die due to non-infectious reasons (pe. expected poor neurologic outcome with therapy restrictions or withdrawal) between day 7 and the end of the intervention period (day 28). In conclusion, a total of 66 patients will be included in the intervention group and will be matched with 66 patients out of the historical control group.
- Conditions
- Sepsis
- Being tested
- Procalcitonin group
- Keywords
- procalcitonin, antibiotic stewardship in ICU, Multidrug resistance, neurocritical care
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Procalcitonin groupDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Procalcitonin group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at day 28
Secondary outcomes (9)
ICU and mortality
We will measure ICU mortality from all causes and infection related ICU mortality by recording date of death
Measured: up to 6 months after inclusion
28-days mortality (from all causes)
We will measure 28-days mortality from all causes and infection related 28-days mortality by recording date of death
Measured: at day 28
Hospital mortality
date of death
Measured: up to 6 months after inclusion
ICU and hospital length of stay
numbers of days in ICU and in hospital respectively
Measured: up to 6 months after inclusion
Duration of Mechanical ventilation
numbers of days alive without ventilatory support (defined as unassisted breathing) during intervention period
Measured: at day 28
Recurrent infection
Number of patients with relapse or superinfection during ICU stay (patients requiring a new course of antibiotic therapy after a former fully completed course)
Measured: at day 28
Reinfection
Number of patients with microbiologically proven reinfection with the same pathogen in ICU
Measured: at day 28
Multidrug Resistance
Incidence of new multidrug resistant bacteria, isolated from specimens taken for routine microbiological assessment during ICU stay
Measured: up to 3 months after inclusion
Multidrug Resistance
Incidence of new multidrug resistant bacteria, isolated from specimens taken for routine microbiological assessment during hospitalisation
Measured: up to 6 months after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2018
- Study start7 May 2018
- Primary completionMay 2020 (estimated)
- Study completionSep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Matched cohort: historical standard of care group (patients from the period January 2016 - April 2018) versus interventional group (patients from May 2018 on)
- Masking
- None (open label)
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- General Hospital Groeninge
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stoffel Lamote, General Hospital Groeninge
- Investigators
- Stoffel Lamote, MD, Principal investigator, AZ Groeninge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03683693
- Sponsor's protocol ID
- AZGS2017164
- Status last verified
- Sep 2018
- First submitted
- 6 Aug 2018
- Last updated
- 25 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 24405683Luyt 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.
PubMed 25405992De 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.
PubMed 26289014Bouadma 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.
PubMed 20097417de 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.
PubMed 26947523Iankova 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.
PubMed 29271844Rhodes 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.
PubMed 28101605Schuetz 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.
PubMed 25581762Kourbeti 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.
PubMed 21851488Lim 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.
PubMed 17448059Brechot 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.
PubMed 26607343
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Procalcitonin to Guide Antibiotic Stop in Neurocritical Care Patients. An Interventional Matched-cohort Study.
- ClinicalTrials.gov ID
- NCT03683693
- Acronym / sponsor ID
- AZGS2017164
- Conditions
- Sepsis
- Keywords
- procalcitonin, antibiotic stewardship in ICU, Multidrug resistance, neurocritical care
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 132 participants (estimated)
- Lead sponsor
- General Hospital GroeningeUniversity, hospital or other
- Study start
- 7 May 2018 (actual)
- Primary completion
- May 2020 (estimated)
- Study completion
- Sep 2020 (estimated)
- First posted
- 25 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single center, before-after, matched cohort study in a ICU of a non-university hospital. It puts the focus on neurocritical care patients as they are prone to infectious complications and these cases are often less straightforward in terms of diagnosis and management. The investigators hypothesise that such an algorithm, in addition to clinical judgement of the ICU physician, will reduce the duration of antibiotic treatment and the overall antibiotic use, could reduce selective pressure, without increase of mortality or recurrent infections.
All patients admitted to ICU with a primary non-infectious neurologic pathology will be screened for eligibility. Eligible patients can be enrolled if they meet all the inclusion criteria, there are no exclusion criteria, a matched control is available and an informed consent has provided by the patient or his or her legal representative. Patients included in the intervention group will be 1:1 matched with a patient out of the historical control group. Therefore, three fixed and two variable criteria for matching will be used. The fixed ones are: 1. pathology (traumatic brain injury; intracerebral/subarachnoid hemorrhage due to cerebral aneurysm or arteriovenous malformation; ischemic stroke; hemorrhagic stroke or other intracranial hemorrhage from; and the whether or not need for intervention (none, endovascular or neurosurgical intervention) . 2. need for mechanical ventilation within the first 12 hours after admission and 3. Glasgow coma scale (GCS) < 8 versus ≥ 8 at ICU admission or before starting sedation or anesthesia.
The two variable criteria are age (with a range of plus or minus 10 years) and the Acute Physiology and Chronic Health Evaluation (APACHE)-II score (with a range of plus or minus 15 points).
Matching will be manually, blinded for the outcome. A control group has been composed by analysing retrospectively patients admitted to our ICU from January 2016 on.
In the intervention group, doctors are additionally provided with PCT levels on regular base and with a non-binding advice on continuation or discontinuation of antibiotic therapy by electronic patient data management system feedback and by the involved microbiologist. The first PCT value will be used just as base-line, without any therapeutic consequence. Measurements will be repeated every 3-4 days, the last one is scheduled at day 27.
Patients in both groups are followed until hospital discharge, allowing assesment of hospital length of stay, hospital mortality and prevalence of multidrug resistance during hospitalisation.
Following data were collected at initiation of the trial : age, sex, BMI, pre-existing comorbidities including presence of known multidrug resistant bacteria before ICU admission, previous location before admission, reason for admission, GCS at admission to ICU, intervention, reason for antibiotic start, day of ICU admission at starting point of the study, APACHE II, the presence and type of organ dysfunction using the sequential organ-failure assessment (SOFA) score and use of mechanical ventilation.
Subsequently, following parameters will be recorded during ICU stay: SOFA score and type of organ or system failure at every PCT measurement, daily need for mechanical ventilation, source of infection when known and results of microbiological cultures. Additionally, the inflammatory biomarkers crp and leucocytosis as well as maximum temperature will be daily registered.
At the end of follow-up, every suspected infectious episode will be sorted by the investigator into four groups: 1. microbiologically documented infection (presence of a clinical and/or radiological infectious focus and pathogen identification); 2. clinically documented infection (presence of a clinical and/or radiological infectious focus, without causative pathogen identification); 3. absence of infection (absence of a clinical or radiological infectious focus) 4. possible infection (all other situations).
Data management will be performed by the investigators or research nurses. Patient's anonymity will be maintained by identifying enrolled patients of both groups with a trial identification number. The list containing the subjects name and allocation numbers are kept in strict confidence. Electronical clinical research files (CRF) or other subject related data will be protected by a password and will be put on a secured server within the hospital. Similarly, written papers (including CRF on paper) containing privacy sensitive information will be kept behind locked doors.
For the power analysis, the ICU databank has been queried, analysing the antibiotic duration of the first, uninterrupted antibiotic course of 74 patients who stayed at least 10 days in ICU in 2016 and got empirical and/or directed antibiotic therapy. A lognormal distribution with a peak value at 11.78 days has been found. After log-transformation, a mean of 2.466 with standard deviation of 0.433 was found.
The investigators aim for 20% antibiotic reduction, supported by the results of the PRORATA and the SAPS trial. This goal is ambitious, but is not unrealistic, taking into account that the study population group is traditionally characterized by high figures of antibiotic consumption. Based on these assumptions, a number of 60 patients in both groups is required for obtaining a power of 80%. This number has been increased with 10%, anticipating for patients who will die due to non-infectious reasons (pe. expected poor neurologic outcome with therapy restrictions or withdrawal) between day 7 and the end of the intervention period (day 28). In conclusion, a total of 66 patients will be included in the intervention group and will be matched with 66 patients out of the historical control group.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Matched cohort: historical standard of care group (patients from the period January 2016 - April 2018) versus interventional group (patients from May 2018 on)
| Arm | Type | Receives |
|---|---|---|
| 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 | Diagnostic Test: Procalcitonin groupICU physician gets on regular base PCT value, what can be used as additive tool in the decision-making for stopping antibiotics. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- patients admitted to the ICU with a primary non-infectious neurological pathology:
- AND
- requiring antibiotics within the first week (day 0 - day 6) after ICU-admission for a suspected bacterial infection
Key exclusion criteria (9 listed)
- 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, ...
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Procalcitonin groupThe 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. | Diagnostic test | Procalcitonin group |
Primary outcome
Antibiotic use
Time frame: at day 28
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.
9 secondary outcomes
ICU and mortality
Time frame: up to 6 months after inclusion
28-days mortality (from all causes)
Time frame: at day 28
Hospital mortality
Time frame: up to 6 months after inclusion
ICU and hospital length of stay
Time frame: up to 6 months after inclusion
Duration of Mechanical ventilation
Time frame: at day 28
Recurrent infection
Time frame: at day 28
Reinfection
Time frame: at day 28
Multidrug Resistance
Time frame: up to 3 months after inclusion
Multidrug Resistance
Time frame: up to 6 months after inclusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2018.
- Background: PubMed 24405683Bell 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.
- Background: PubMed 25405992Luyt 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.
- Background: PubMed 26289014De 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.
- Background: PubMed 20097417Bouadma 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.
- Background: PubMed 26947523de 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.
- Background: PubMed 29271844Iankova 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.
- Background: PubMed 28101605Rhodes 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.
- Background: PubMed 25581762Schuetz 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.
- Background: PubMed 21851488Kourbeti 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.
- Background: PubMed 17448059Lim 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.
- Background: PubMed 26607343Brechot 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.
- World Health Organisation (WHO) Collaborating Centre for Drug Statistics Methodology 2015Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stoffel Lamote, MD principal investigator
AZ Groeninge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Procalcitonin group in people with Sepsis, run by General Hospital Groeninge at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stoffel Lamote, MD (3256633055, stoffel.lamote@azgroeninge.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antibiotic use (time frame: at day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03683693, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2018.