Septic ShockPhase 3DECRISSNCT04742764

Extracorporal Cytokin Removal in Septic Shock: a Prospective, Randomized, Multicenter Clinical Trial

A Phase 3 study testing Standard medical therapy, Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hours and Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hours in people with Septic Shock, run by University of Pecs at 1 site in Hungary.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Septic Shock
What is being tested?: Standard medical therapy, Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hours and Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hours
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 135 participants
Where: 1 siteHungary
Study dates: 1 Jan 2024to 31 Oct 2027
Phase: Phase 3
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 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Septic shock as defined by the Sepsis-3 criteria
Septic shock both medical or surgical ethiology (except for re-operation)
APACHE > 25
Mechanical ventilation
Norepinephrine requirement ≥0.4 µg/kg/min for at least 30 minutes, when hypovolemia is highly unlikely as indicated by invasive hemodynamic measurements assessed by the attending physician
Invasive hemodynamic monitoring to determine cardiac output and derived variables
Procalcitonin level ≥ 10 ng/ml
Inclusion within 6 - 24 hours after the onset of vasopressor need and after all standard therapeutic measures have been implemented without clinical improvement (i.e.: the shock is considered refractory)

Who cannot join

Patients under 18 years and over 80
Lack of health insurance
Pregnancy
Standard guideline-based medical treatment not exhausted (detailed below at 3.6) standard medical therapy)
End stage organ failure
New York Heart Association Class IV.

Show all 20Show fewer

Chronic renal failure with eGFR < 15 ml/min/1,73 m2
End-stage liver disease (MELD score >30, Child-Pugh score Class C
Unlikely survival for 24 hours according to the attending physician
Acute onset of hemato-oncological illness
Post cardiopulmonary resuscitation care
Re-operation in context with the septic insult
Immunosuppression
systemic steroid therapy (>10 mg prednisolon/day)
immunosuppressive agents (i.e.: methotrexate, azathioprine, cyclosporin, tacrolimus, cyclophosphamide)
Human immunodeficiency virus infection (active AIDS): HIV-VL > 50 copies/mL
Patients with transplanted vital organs
Thrombocytopenia (<20.000/ml)
More than 10%-of body surface area with a third-degree burn
Acute coronary syndrome

Trial locations and contacts

1 site in 1 country.

Hungary1 site

Institute for Translational Medicine, University of Pécs
Pécs, 7624

Other trials in Hungary

About this study

Official title: Dosing of Extracorporeal Cytokine Removal In Septic Shock (DECRISS): a Prospective, Randomized, Multicenter Clinical Trial

Sepsis and septic shock have mortality rates between 20-50%. When standard therapeutic measures fail to improve patients' condition, additional therapeutic alternatives are applied to reduce morbidity and mortality. One of the most recent alternatives is extracorporeal cytokine hemoadsorption. One of the most tested devices is CytoSorb, however, there are a lot of open questions, such timing, dosing and of course its overall efficacy. This study aims to compare the efficacy of standard medical therapy (Group A, SMT) and continuous extracorporeal cytokine removal with CytoSorb therapy in patients with early refractory septic shock. Furthermore, we compare the dosing of CytoSorb adsorber device - as the cartridge will be changed in every (12 Group B) or 24 hours (Group C).

Conditions: Septic Shock
Being tested: Standard medical therapy, Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hours, Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hours
Keywords: sepsis, septic shock, cytosorb, cytokine removal
Medical subject headings: Shock, Septic, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Standard medical therapyCombination product
Standard medical therapy (according to the Surviving Sepsis Campaign) will include standard monitoring (pulseoximetry, 5-lead ECG, continuous invasive blood pressure monitoring, central venous cannulation and 24 with PiCCO-technology. Norepinephrine as a vasopressor and dobutamine - if needed - as an inotrope will be administered by the attending physician.
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hoursDevice
Standard medical therapy, as discussed above will be applied. Furthermore, Cytosorb will be administered as soon as it is possible after randomization but not later than 2 hour (start of the treatment, T0). In a blood pump circuit in pre-haemofilter position, using a kidney replacement device of Fresenius Multifiltrate as a solo therapy or in combination with renal replacement therapy. It will be run in CVVHD, CVVHDF or CVVH mode with a 150 and 200 ml/min blood flow. Anticoagulation will be applied intravenously with heparin, low molecular weight heparin or citrate. The aim of the pump flow rate will be 100-400 mL/min, and the flow rate will be recorded. Possible shock reversal will be assessed by the physician attending. Adsorber cartridges will be changed in every 12 hours. End of the study period (Te): 12 hours after shock reversal, death of the patient, or maximum of five days, whichever happens first.
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hoursDevice
The standard medical therapy and method of Cytosorb treatment as detailed above will be applied. Adsorber cartridges will be changed in every 24 hours.

Study groups in NCT04742764
Study group	Role	What they receive
Group A	Active comparator	Patients randomized to standard medical therapy. Receives: Combination Product: Standard medical therapy
Group B	Active comparator	Patients randomized to cytokine removal therapy with Cytosorb, with the adsorber device changed in every 12 hours. Receives: Device: Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hours
Group C	Active comparator	Patients randomized to cytokine removal therapy with Cytosorb, with the adsorber device changed in every 24 hours. Receives: Device: Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hours

What is being measured

The primary outcome is the main question the study is designed to answer.

Shock reversal
Proportion of patients achieving shock reversal, defined as follows:
no need (or minimal need, meaning max. the 10% of the maximum dose) of vasopressore for 3 hours, with haemodynamic measurements, and arterial, central venous blood gas analysis, arterial lactate level measurement, venous and arterial pCO2-gap and O2 saturation measurements to confirm cardiorespiratory stability
Measured: At the time of shock reversal assessed up to 5 days
Time to shock reversal
The time from the start of the treatment (T0) until shock reversal
Measured: From the start of the treatment until shock reversal assessed up to 5 days

Secondary outcomes (32)

Procalcitonine level
Absolute level of procalcitonine
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in procalcitonine level
Change in procalcitonine level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-6 level
Absolute level of interleukin-6
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-6 level
Change in interleukin-6 level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
C-reactive protein level
Absolute level of C-reactive protein
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in C-reactive protein level
Change in C-reactive protein level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-1 level
Absolute level of interleukin-1
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-1 level
Change in interleukin-1 level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-1ra level
Absolute level of interleukin-1ra
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-1ra level
Change in interleukin-1ra level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-8 level
Absolute level of interleukin-8
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-8 level
Change in interleukin-8 level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-10 level
Absolute level of interleukin-10
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-10 level
Change in interleukin-10 level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Tumor necrosis factor alpha level
Absolute level of tumor necrosis factor alpha
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in tumor necrosis factor alpha level
Change in tumor necrosis factor alpha level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Syndecan-1 level
Absolute level of syndecan-1
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in syndecan-1 level
Change in syndecan-1 level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Heparan sulphate level
Absolute level of heparan sulphate
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in heparan sulphate level
Change in heparan sulphate level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Arterial lactate levels
Absolute level of arterial lactate levels
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in arterial lactate levels level
Change in arterial lactate level from the start of the treatment until the end of the study period
Measured: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in SOFA score
Change in SOFA score from the start of the treatment until the end of the study period
Measured: From the start of the treatment until the end of the treatment assessed up to 5 days
Change in extravascular lung water (EVLW)
Change in extravascular lung water (EVLW) from the start of the treatment until the end of the study period
Measured: From the start of the treatment until the end of the treatment assessed up to 5 days
Duration of mechanical ventilation
Duration of mechanical ventilation given in days
Measured: From the start of the treatment until the end of the treatment assessed up to 5 days
Duration of catecholamine requirement
Duration of catecholamine requirement given in days
Measured: From the start of the catecholamine requirement until the end of the catecholamine requirement assessed up to 5 days
Duration of renal replacement therapy
Duration of renal replacement therapy given in days
Measured: From the start of the renal replacement therapy requirement until the end of the renal replacement therapy requirement assessed up to 90+/-7 days at the second follow-up visit
Need for dialysis
Rate of patients, who require dialysis
Measured: day 28±7, day 90±7
Length of internsive care unit stay
Length of intensive care unit stay given in days
Measured: From admission to intensive care unit until the end of intensive care unit assessed at study completion an avarage of 90 days
Length of hospital stay
Length of hospital stay given in days
Measured: From admission to the hospital until the end of hospital stay assessed at study completion an avarage of 90 days
Survival
Rate of surviving patients
Measured: Rate if surviving patients assessed at death, or study completion which ever happens first, up to 90 +/-7 days
Adverse events
Rate of patients experiencing adverse events, or device deficiencies
Measured: Recorded at the occurrance of adverse events, and study completion up to 90 +/- 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 202431 Oct 2027

First posted8 Feb 2021
Study start1 Jan 2024 (estimated)
Primary completion31 Oct 2026 (estimated)
Study completion31 Oct 2027 (estimated)

Why it stopped: The human resources required to start enrollment were not available anymore.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (47)Papers the sponsor has linked to this study.
Other trials for Septic ShockStudies 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Prospective, randomized, controlled, three-arm, open-label, international, multi-centre, phase III study
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 135 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04742764
Sponsor's protocol ID: OGYÉI/65049/2020
Acronym: DECRISS
Status last verified: Apr 2023
First submitted: 26 Jan 2021
Last updated: 20 Apr 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Sogayar AM, Machado FR, Rea-Neto A, Dornas A, Grion CM, Lobo SM, Tura BR, Silva CL, Cal RG, Beer I, Michels V, Safi J, Kayath M, Silva E; Costs Study Group - Latin American Sepsis Institute. A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units. Pharmacoeconomics. 2008;26(5):425-34. doi: 10.2165/00019053-200826050-00006.
PubMed 18429658
Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, Meshaka P, Cheval C, Thuong M, Troche G, Garrouste-Orgeas M, Timsit JF. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005 Mar;20(1):46-58. doi: 10.1016/j.jcrc.2004.10.005.
PubMed 16015516
Khwannimit B, Bhurayanontachai R. The direct costs of intensive care management and risk factors for financial burden of patients with severe sepsis and septic shock. J Crit Care. 2015 Oct;30(5):929-34. doi: 10.1016/j.jcrc.2015.05.011. Epub 2015 May 20.
PubMed 26051981
Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C, Remick DG. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 2013 Jul;93(3):1247-88. doi: 10.1152/physrev.00037.2012.
PubMed 23899564
Kwan A, Hubank M, Rashid A, Klein N, Peters MJ. Transcriptional instability during evolving sepsis may limit biomarker based risk stratification. PLoS One. 2013;8(3):e60501. doi: 10.1371/journal.pone.0060501. Epub 2013 Mar 27.
PubMed 23544148
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006 Feb 24;124(4):783-801. doi: 10.1016/j.cell.2006.02.015.
PubMed 16497588
Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013 Dec;13(12):862-74. doi: 10.1038/nri3552. Epub 2013 Nov 15.
PubMed 24232462
Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets--an updated view. Mediators Inflamm. 2013;2013:165974. doi: 10.1155/2013/165974. Epub 2013 Jun 18.
PubMed 23853427
Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr Opin Immunol. 2013 Aug;25(4):477-83. doi: 10.1016/j.coi.2013.05.006. Epub 2013 May 28.
PubMed 23725873
Sharawy N. Vasoplegia in septic shock: do we really fight the right enemy? J Crit Care. 2014 Feb;29(1):83-7. doi: 10.1016/j.jcrc.2013.08.021. Epub 2013 Oct 4.
PubMed 24095623
Laszlo I, Trasy D, Molnar Z, Fazakas J. Sepsis: From Pathophysiology to Individualized Patient Care. J Immunol Res. 2015;2015:510436. doi: 10.1155/2015/510436. Epub 2015 Jul 15.
PubMed 26258150
Bellomo R, Baldwin I, Ronco C. Extracorporeal blood purification therapy for sepsis and systemic inflammation: its biological rationale. Contrib Nephrol. 2001;(132):367-74. doi: 10.1159/000060105.
PubMed 11395904
Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, Malcangi V, Petrini F, Volta G, Bobbio Pallavicini FM, Rottoli F, Giunta F, Ronco C. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009 Jun 17;301(23):2445-52. doi: 10.1001/jama.2009.856.
PubMed 19531784
Kreymann KG, de Heer G, Nierhaus A, Kluge S. Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med. 2007 Dec;35(12):2677-85.
PubMed 18074464
Basu R, Pathak S, Goyal J, Chaudhry R, Goel RB, Barwal A. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study. Indian J Crit Care Med. 2014 Dec;18(12):822-4. doi: 10.4103/0972-5229.146321.
PubMed 25538418

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 20 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Dosing of Extracorporeal Cytokine Removal In Septic Shock (DECRISS): a Prospective, Randomized, Multicenter Clinical Trial
ClinicalTrials.gov ID: NCT04742764
Acronym / sponsor ID: DECRISS / OGYÉI/65049/2020
Conditions: Septic Shock
Keywords: sepsis, septic shock, cytosorb, cytokine removal
Phase: Phase 3
Study type: Interventional
Recruitment status: SuspendedReason stopped: The human resources required to start enrollment were not available anymore.
Enrolment: 135 participants (estimated)
Lead sponsor: University of PecsUniversity, hospital or other
Study start: 1 Jan 2024 (estimated)
Primary completion: 31 Oct 2026 (estimated)
Study completion: 31 Oct 2027 (estimated)
First posted: 8 Feb 2021 (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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 3
Model description: Prospective, randomized, controlled, three-arm, open-label, international, multi-centre, phase III study

Arm	Type	Receives
Group A	Active comparator	Combination Product: Standard medical therapyPatients randomized to standard medical therapy.
Group B	Active comparator	Device: Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hoursPatients randomized to cytokine removal therapy with Cytosorb, with the adsorber device changed in every 12 hours.
Group C	Active comparator	Device: Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hoursPatients randomized to cytokine removal therapy with Cytosorb, with the adsorber device changed in every 24 hours.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Septic shock as defined by the Sepsis-3 criteria
Septic shock both medical or surgical ethiology (except for re-operation)
APACHE > 25
Mechanical ventilation
Norepinephrine requirement ≥0.4 µg/kg/min for at least 30 minutes, when hypovolemia is highly unlikely as indicated by invasive hemodynamic measurements assessed by the attending physician

Key exclusion criteria (20 listed)

Patients under 18 years and over 80
Lack of health insurance
Pregnancy
Standard guideline-based medical treatment not exhausted (detailed below at 3.6) standard medical therapy)
End stage organ failure

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
Standard medical therapyStandard medical therapy (according to the Surviving Sepsis Campaign) will include standard monitoring (pulseoximetry, 5-lead ECG, continuous invasive blood pressure monitoring, central venous cannulation and 24 with PiCCO-technology. Norepinephrine as a vasopressor and dobutamine - if needed - as an inotrope will be administered by the attending physician.	Combination product	Group A
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hoursStandard medical therapy, as discussed above will be applied. Furthermore, Cytosorb will be administered as soon as it is possible after randomization but not later than 2 hour (start of the treatment, T0). In a blood pump circuit in pre-haemofilter position, using a kidney replacement device of Fresenius Multifiltrate as a solo therapy or in combination with renal replacement therapy. It will be run in CVVHD, CVVHDF or CVVH mode with a 150 and 200 ml/min blood flow. Anticoagulation will be applied intravenously with heparin, low molecular weight heparin or citrate. The aim of the pump flow rate will be 100-400 mL/min, and the flow rate will be recorded. Possible shock reversal will be assessed by the physician attending. Adsorber cartridges will be changed in every 12 hours. End of the study period (Te): 12 hours after shock reversal, death of the patient, or maximum of five days, whichever happens first.	Device	Group B
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hoursThe standard medical therapy and method of Cytosorb treatment as detailed above will be applied. Adsorber cartridges will be changed in every 24 hours.	Device	Group C

Primary outcome

Shock reversal
Time frame: At the time of shock reversal assessed up to 5 days
Proportion of patients achieving shock reversal, defined as follows: no need (or minimal need, meaning max. the 10% of the maximum dose) of vasopressore for 3 hours, with haemodynamic measurements, and arterial, central venous blood gas analysis, arterial lactate level measurement, venous and arterial pCO2-gap and O2 saturation measurements to confirm cardiorespiratory stability
Time to shock reversal
Time frame: From the start of the treatment until shock reversal assessed up to 5 days
The time from the start of the treatment (T0) until shock reversal

32 secondary outcomes

Procalcitonine level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in procalcitonine level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-6 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-6 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
C-reactive protein level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in C-reactive protein level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-1 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-1 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-1ra level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-1ra level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-8 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-8 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Interleukin-10 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in interleukin-10 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Tumor necrosis factor alpha level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in tumor necrosis factor alpha level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Syndecan-1 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in syndecan-1 level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Heparan sulphate level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in heparan sulphate level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Arterial lactate levels
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in arterial lactate levels level
Time frame: 0, 6, 12,24 hours after the start of the treatment, then daily until the end of study period assessed up to 90 +/- 7 days at second follow-up visit
Change in SOFA score
Time frame: From the start of the treatment until the end of the treatment assessed up to 5 days
Change in extravascular lung water (EVLW)
Time frame: From the start of the treatment until the end of the treatment assessed up to 5 days
Duration of mechanical ventilation
Time frame: From the start of the treatment until the end of the treatment assessed up to 5 days
Duration of catecholamine requirement
Time frame: From the start of the catecholamine requirement until the end of the catecholamine requirement assessed up to 5 days
Duration of renal replacement therapy
Time frame: From the start of the renal replacement therapy requirement until the end of the renal replacement therapy requirement assessed up to 90+/-7 days at the second follow-up visit
Need for dialysis
Time frame: day 28±7, day 90±7
Length of internsive care unit stay
Time frame: From admission to intensive care unit until the end of intensive care unit assessed at study completion an avarage of 90 days
Length of hospital stay
Time frame: From admission to the hospital until the end of hospital stay assessed at study completion an avarage of 90 days
Survival
Time frame: Rate if surviving patients assessed at death, or study completion which ever happens first, up to 90 +/-7 days
Adverse events
Time frame: Recorded at the occurrance of adverse events, and study completion up to 90 +/- 7 days

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2023.
Background: PubMed 18429658Sogayar AM, Machado FR, Rea-Neto A, Dornas A, Grion CM, Lobo SM, Tura BR, Silva CL, Cal RG, Beer I, Michels V, Safi J, Kayath M, Silva E; Costs Study Group - Latin American Sepsis Institute. A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units. Pharmacoeconomics. 2008;26(5):425-34. doi: 10.2165/00019053-200826050-00006.
Background: PubMed 16015516Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, Meshaka P, Cheval C, Thuong M, Troche G, Garrouste-Orgeas M, Timsit JF. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005 Mar;20(1):46-58. doi: 10.1016/j.jcrc.2004.10.005.
Background: PubMed 26051981Khwannimit B, Bhurayanontachai R. The direct costs of intensive care management and risk factors for financial burden of patients with severe sepsis and septic shock. J Crit Care. 2015 Oct;30(5):929-34. doi: 10.1016/j.jcrc.2015.05.011. Epub 2015 May 20.
Background: PubMed 23899564Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C, Remick DG. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 2013 Jul;93(3):1247-88. doi: 10.1152/physrev.00037.2012.
Background: PubMed 23544148Kwan A, Hubank M, Rashid A, Klein N, Peters MJ. Transcriptional instability during evolving sepsis may limit biomarker based risk stratification. PLoS One. 2013;8(3):e60501. doi: 10.1371/journal.pone.0060501. Epub 2013 Mar 27.
Background: PubMed 16497588Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006 Feb 24;124(4):783-801. doi: 10.1016/j.cell.2006.02.015.
Background: PubMed 24232462Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013 Dec;13(12):862-74. doi: 10.1038/nri3552. Epub 2013 Nov 15.
Background: PubMed 23853427Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets--an updated view. Mediators Inflamm. 2013;2013:165974. doi: 10.1155/2013/165974. Epub 2013 Jun 18.
Background: PubMed 23725873Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr Opin Immunol. 2013 Aug;25(4):477-83. doi: 10.1016/j.coi.2013.05.006. Epub 2013 May 28.
Background: PubMed 24095623Sharawy N. Vasoplegia in septic shock: do we really fight the right enemy? J Crit Care. 2014 Feb;29(1):83-7. doi: 10.1016/j.jcrc.2013.08.021. Epub 2013 Oct 4.
Background: PubMed 26258150Laszlo I, Trasy D, Molnar Z, Fazakas J. Sepsis: From Pathophysiology to Individualized Patient Care. J Immunol Res. 2015;2015:510436. doi: 10.1155/2015/510436. Epub 2015 Jul 15.
Background: PubMed 11395904Bellomo R, Baldwin I, Ronco C. Extracorporeal blood purification therapy for sepsis and systemic inflammation: its biological rationale. Contrib Nephrol. 2001;(132):367-74. doi: 10.1159/000060105.
Individual participant dataSharing planned: No

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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.

Péter Hegyi, MD, PhD, DSc principal investigator

Insitute for Translational Medicine, University of Pécs, Medical School, Pécs, Hungary

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 20 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: paused, as of the sponsor's last update on 20 Apr 2023. 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 Hungary. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Shock reversal (time frame: At the time of shock reversal assessed up to 5 days). The study lists 2 primary outcomes in all. 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 NCT04742764, which also lists 47 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 20 Apr 2023.