CLinical Efficacy of Hemoperfusion With a Cytokine Adsorber in Norepinephrine-Resistant SEptic Shock
- Conditions
- Septic ShockCytokine Storm
- Interventions
- Device: HA-330 Disposable Hemoperfusion Cartridge (Jafron, China)
- Registration Number
- NCT05136183
- Lead Sponsor
- Mahidol University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 200
- 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of care, with hemoperfusion with HA-330 HA-330 Disposable Hemoperfusion Cartridge (Jafron, China) 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'
- Primary Outcome Measures
Name Time Method 28-day mortality 28 days
- Secondary Outcome Measures
Name Time Method Acute Physiology and Chronic Health Evaluation score (APACHE II) at Hour 24, Hour 48 and Day 7 7 days Ventilator-free day 28 days 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 daysHospital mortality up to 24 weeks Vasopressor-free day 28 days 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 daysVasoactive inotropic score at Hour 24, Hour 48 and Day 7 7 days Sequential Organ Failure Assessment score (SOFA) at Hour 24, Hour 48 and Day 7 7 days Serum C-reactive protein level at Hour 24 and Hour 48 48 hours ICU mortality up to 24 weeks ICU-free day 28 days 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 daysShock reversal at Hour 6 6 hours 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 morePlasma Interleukin-6 level at Hour 24 and Hour 48 48 hours Renal replacement therapy (RRT) -free day 28 days 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 daysArterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at Hour 24, Hour 48 and Day 7 7 days Adverse events 28 days
Trial Locations
- Locations (1)
Faculty of Medicine Siriraj Hospital
🇹🇭Bangkok Noi, Bangkok, Thailand