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CLinical Efficacy of Hemoperfusion With a Cytokine Adsorber in Norepinephrine-Resistant SEptic Shock (CLEANSE)

Primary Purpose

Septic Shock, Cytokine Storm

Status
Recruiting
Phase
Not Applicable
Locations
Thailand
Study Type
Interventional
Intervention
HA-330 Disposable Hemoperfusion Cartridge (Jafron, China)
Sponsored by
Mahidol University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Sepsis, Septic shock, Hemoperfusion, Blood purification, HA-330

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Septic shock patients, according to The Third International Consensus Definitions for Sepsis and Septic Shock and
  • Is receiving intravenous norepinephrine 0.2 mcg/kg/min or more, or equivalent dose of other vasoactive agents

Exclusion Criteria:

One who has

  • acute coronary syndrome
  • life-threatening arrhythmias
  • acute ischemic stroke
  • life-threatening, uncontrolled bleeding
  • underlying conditions judged to have with limited life expectancy (less than 6 months) by primary physicians

One who is

  • judged by treating physicians as in moribund state and expected not to survive to 24 hours regardless of treatment given
  • known to be pregnant at enrollment
  • not in the competent state to give informed consent and not having relatives to do so
  • not willing to pursue intensive medical therapy considered standard of care for patients with septic shock

Sites / Locations

  • Faculty of Medicine Siriraj HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Standard of care

Standard of care, with hemoperfusion with HA-330

Arm Description

Patients randomized to this arm are treated with standard of care for patients with septic shock, including Fluid resuscitation and vasoactive agents Hemodynamic monitoring in intensive care units Antibiotics and infection source control, when applicable Supportive therapies and devices, including mechanical ventilation and renal replacement therapy Immunoregulatory medications, including systemic corticosteroids All treatment provided are according to treating physicians

Patients randomized to this arm are treated with standard of care for patients with septic shock as described for 'Standard of care' arm, along with hemoperfusion with HA-330 Disposable Hemoperfusion Cartridge, as detailed under 'Interventions'

Outcomes

Primary Outcome Measures

28-day mortality

Secondary Outcome Measures

ICU mortality
Hospital mortality
ICU-free day
Number of days that patient is alive and not admitted in the ICU in the first 28 days, with the day of randomization defined as Day 0 In case of ICU readmission, the days from the final ICU discharge within 28 days are counted. All 28-day non-survivors are counted 0, irrespective of their place of care at the time of death, and censored observations after 28 days
Vasopressor-free day
Number of days that patient is alive after successful discontinuation of vasoactive agents in the first 28 days, with the day of randomization defined as Day 0 Successful discontinuation of vasoactive agents is defined as discontinuation of vasoactive agents without resumption until Day 28 or until hospital discharge, whichever is first. In case of multiple periods of vasoactive agents use, the days from the final discontinuation of vasoactive agents are counted. All 28-day non-survivors are counted 0, irrespective of their use of vasoactive agents at the time of death, and censored observations after 28 days
Ventilator-free day
Number of days that patient is alive after successful liberation of mechanical ventilation in the first 28 days, with the day of randomization defined as Day 0 Successful liberation of mechanical ventilation is defined as discontinuation mechanical ventilation (either via orotracheal or tracheostomy tube) for 48 hours or more. Non-invasive positive pressure ventilation is not regarded as mechanical ventilation. In case of multiple periods of mechanical ventilation, the days from the final successful liberation of mechanical ventilation within 28 days are counted. All 28-day non-survivors are counted 0, irrespective of their ventilation status at the time of death, and censored observations after 28 days
Renal replacement therapy (RRT) -free day
Number of days that patient is alive after successful discontinuation of renal-replacement therapy in the first 28 days, with the day of randomization defined as Day 0 Successful discontinuation of renal-replacement therapy is defined as discontinuation of all modes of renal-replacement therapy without resumption for at least 7 days and until Day 28 or until hospital discharge, whichever is first. Hemoperfusion according to treatment protocol in 'Standard of care and hemoperfusion with HA-330' arm is not counted as renal-replacement therapy. All 28-day non-survivors are counted 0, irrespective of their use of renal-replacement therapy at the time of death, and censored observations after 28 days
Vasoactive inotropic score at Hour 24, Hour 48 and Day 7
Shock reversal at Hour 6
Shock reversal is defined as mean arterial pressure at or more than 65 mmHg with one of the following: Reduction of serum lactate level of 20% or more Hourly urine output of 0.5 mL/kg or more
Arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at Hour 24, Hour 48 and Day 7
Acute Physiology and Chronic Health Evaluation score (APACHE II) at Hour 24, Hour 48 and Day 7
Sequential Organ Failure Assessment score (SOFA) at Hour 24, Hour 48 and Day 7
Serum C-reactive protein level at Hour 24 and Hour 48
Plasma Interleukin-6 level at Hour 24 and Hour 48
Adverse events

Full Information

First Posted
November 8, 2021
Last Updated
November 25, 2021
Sponsor
Mahidol University
Collaborators
Faculty of Medicine Siriraj Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05136183
Brief Title
CLinical Efficacy of Hemoperfusion With a Cytokine Adsorber in Norepinephrine-Resistant SEptic Shock
Acronym
CLEANSE
Official Title
CLinical Efficacy of Hemoperfusion With a Cytokine Adsorber in Norepinephrine-Resistant SEptic Shock
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2021 (Anticipated)
Primary Completion Date
November 30, 2022 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mahidol University
Collaborators
Faculty of Medicine Siriraj Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Sepsis and septic shock are major causes of ICU admission worldwide. Despite recent advances in treatment, including targeted resuscitation and timely use of antimicrobial agents, mortality of ICU patients with septic shock remains steadily high. Especially in those requiring high dosage of vasopressors, whose 28-day mortality rate could reach 60%. The pathophysiology of septic shock emphasizes on the role of dysregulated host immune response towards inciting microbes, producing excessive inflammatory cytokines which lead to tissue damage and subsequent organ failures. Multiple therapies targeting the overwhelming inflammatory response in patients with septic shock have been studied (ref). While some showed promising results in modulating inflammation in observational studies (ref), none other than systemic corticosteroids lead to better clinical outcomes in the randomized controlled studies. The reasons for their failures are the complexity of the inflammation cascades, where treatments specifically targeting parts of the process may not be able to achieve meaningful effects. Extracorporeal blood purification therapy is an adjunctive treatment option more extensively studied over the last decade. By passing patients' blood or plasma through specifically developed absorber, various inflammatory cytokines are absorbed to resins inside the devices and removed from the circulation. Decreasing levels of inflammatory cytokines may subsequently attenuate systemic inflammation leading to shock reversal and better survival. HA-330 disposable hemoperfusion cartridge (Jafron®, China) is an absorber targeting hyper-inflammatory states including septic shock. It is designed to nonspecifically absorb molecules with molecular weight 10-60 kilo-Dalton, making it effective for removing various pro-inflammatory cytokines and potentially modulating the inflammatory cascade. Previous randomized study in patients with sepsis compared between the add-on 3 daily session of hemoperfusion with HA-330 adsorber and the standard therapy . .Circulating interleukin-6 and interleukin-8 levels of patients underwent hemoperfusion significantly reduced after two sessions when compared to baseline. Their values on day 3 were also significantly lower than those of the control group. Adjunctive hemoperfusion were associated with lower ICU mortality, butno significant difference in hospital and 28-day mortality between the two groups(ref). However, approximately 50% of enrolled patients had sepsis without shock. Generalization of the findings to more severe cohorts of septic shock patients are therefore limited. Patients with septic shock have higher cytokines level than septic patients without shock. Hence, they are theoretically more likely to benefit from therapies aiming to reduce cytokine levels. We hypothesize that adjunctive hemoperfusion with HA-330 adsorber would be associated with better outcomes in a more severe group of patients with septic shock.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock, Cytokine Storm
Keywords
Sepsis, Septic shock, Hemoperfusion, Blood purification, HA-330

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
Patients randomized to this arm are treated with standard of care for patients with septic shock, including Fluid resuscitation and vasoactive agents Hemodynamic monitoring in intensive care units Antibiotics and infection source control, when applicable Supportive therapies and devices, including mechanical ventilation and renal replacement therapy Immunoregulatory medications, including systemic corticosteroids All treatment provided are according to treating physicians
Arm Title
Standard of care, with hemoperfusion with HA-330
Arm Type
Experimental
Arm Description
Patients randomized to this arm are treated with standard of care for patients with septic shock as described for 'Standard of care' arm, along with hemoperfusion with HA-330 Disposable Hemoperfusion Cartridge, as detailed under 'Interventions'
Intervention Type
Device
Intervention Name(s)
HA-330 Disposable Hemoperfusion Cartridge (Jafron, China)
Intervention Description
If no appropriate vascular access available, a double lumen catheter is placed by treating physicians, under ultrasonographic guidance. Two sessions of hemoperfusion using HA-330 Disposable Hemoperfusion Cartridge are performed 24 hours apart. Hemoperfusion is performed using either hemoperfusion or continuous renal replacement therapy machine. The optimal blood flow rate is 150-200 mL/min. The duration for each session in 2 hours. No systemic anticoagulant is given except for priming of the cartridge according to manufacturer recommendations. The first hemoperfusion session is recommended to be initiated within 12 hours after randomization.
Primary Outcome Measure Information:
Title
28-day mortality
Time Frame
28 days
Secondary Outcome Measure Information:
Title
ICU mortality
Time Frame
up to 24 weeks
Title
Hospital mortality
Time Frame
up to 24 weeks
Title
ICU-free day
Description
Number of days that patient is alive and not admitted in the ICU in the first 28 days, with the day of randomization defined as Day 0 In case of ICU readmission, the days from the final ICU discharge within 28 days are counted. All 28-day non-survivors are counted 0, irrespective of their place of care at the time of death, and censored observations after 28 days
Time Frame
28 days
Title
Vasopressor-free day
Description
Number of days that patient is alive after successful discontinuation of vasoactive agents in the first 28 days, with the day of randomization defined as Day 0 Successful discontinuation of vasoactive agents is defined as discontinuation of vasoactive agents without resumption until Day 28 or until hospital discharge, whichever is first. In case of multiple periods of vasoactive agents use, the days from the final discontinuation of vasoactive agents are counted. All 28-day non-survivors are counted 0, irrespective of their use of vasoactive agents at the time of death, and censored observations after 28 days
Time Frame
28 days
Title
Ventilator-free day
Description
Number of days that patient is alive after successful liberation of mechanical ventilation in the first 28 days, with the day of randomization defined as Day 0 Successful liberation of mechanical ventilation is defined as discontinuation mechanical ventilation (either via orotracheal or tracheostomy tube) for 48 hours or more. Non-invasive positive pressure ventilation is not regarded as mechanical ventilation. In case of multiple periods of mechanical ventilation, the days from the final successful liberation of mechanical ventilation within 28 days are counted. All 28-day non-survivors are counted 0, irrespective of their ventilation status at the time of death, and censored observations after 28 days
Time Frame
28 days
Title
Renal replacement therapy (RRT) -free day
Description
Number of days that patient is alive after successful discontinuation of renal-replacement therapy in the first 28 days, with the day of randomization defined as Day 0 Successful discontinuation of renal-replacement therapy is defined as discontinuation of all modes of renal-replacement therapy without resumption for at least 7 days and until Day 28 or until hospital discharge, whichever is first. Hemoperfusion according to treatment protocol in 'Standard of care and hemoperfusion with HA-330' arm is not counted as renal-replacement therapy. All 28-day non-survivors are counted 0, irrespective of their use of renal-replacement therapy at the time of death, and censored observations after 28 days
Time Frame
28 days
Title
Vasoactive inotropic score at Hour 24, Hour 48 and Day 7
Time Frame
7 days
Title
Shock reversal at Hour 6
Description
Shock reversal is defined as mean arterial pressure at or more than 65 mmHg with one of the following: Reduction of serum lactate level of 20% or more Hourly urine output of 0.5 mL/kg or more
Time Frame
6 hours
Title
Arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at Hour 24, Hour 48 and Day 7
Time Frame
7 days
Title
Acute Physiology and Chronic Health Evaluation score (APACHE II) at Hour 24, Hour 48 and Day 7
Time Frame
7 days
Title
Sequential Organ Failure Assessment score (SOFA) at Hour 24, Hour 48 and Day 7
Time Frame
7 days
Title
Serum C-reactive protein level at Hour 24 and Hour 48
Time Frame
48 hours
Title
Plasma Interleukin-6 level at Hour 24 and Hour 48
Time Frame
48 hours
Title
Adverse events
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Septic shock patients, according to The Third International Consensus Definitions for Sepsis and Septic Shock and Is receiving intravenous norepinephrine 0.2 mcg/kg/min or more, or equivalent dose of other vasoactive agents Exclusion Criteria: One who has acute coronary syndrome life-threatening arrhythmias acute ischemic stroke life-threatening, uncontrolled bleeding underlying conditions judged to have with limited life expectancy (less than 6 months) by primary physicians One who is judged by treating physicians as in moribund state and expected not to survive to 24 hours regardless of treatment given known to be pregnant at enrollment not in the competent state to give informed consent and not having relatives to do so not willing to pursue intensive medical therapy considered standard of care for patients with septic shock
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ranistha Ratanarat, MD
Phone
+66 2419 7767
Email
ranittha@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Nattapat Wongtirawit, MD
Phone
+66 2419 7767
Email
n.wongtirawit@gmail.com
Facility Information:
Facility Name
Faculty of Medicine Siriraj Hospital
City
Bangkok Noi
State/Province
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nattapat Wongtirawit, MD
Phone
+66 2419 7767
Email
n.wongtirawit@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31151462
Citation
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Results Reference
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CLinical Efficacy of Hemoperfusion With a Cytokine Adsorber in Norepinephrine-Resistant SEptic Shock

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