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

NCT05136183 | Unknown

• 1 other identifier: SI040/2021
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Septic Shock; Cytokine Storm

Keywords

Sepsis; Septic shock; Hemoperfusion; Blood purification; HA-330

Outcome Measures

Primary Outcomes (1)

• 28-day mortality

  28 days

Secondary Outcomes (14)

• ICU mortality

  up to 24 weeks

• Hospital mortality

  up to 24 weeks

• ICU-free day

  28 days

• Vasopressor-free day

  28 days

• Ventilator-free day

  28 days

Study Arms (2)

Standard of care

NO INTERVENTION

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

Standard of care, with hemoperfusion with HA-330

EXPERIMENTAL

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'

Device: HA-330 Disposable Hemoperfusion Cartridge (Jafron, China)

Interventions

HA-330 Disposable Hemoperfusion Cartridge (Jafron, China) DEVICE

* 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.

Standard of care, with hemoperfusion with HA-330

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mahidol University: lead
• Siriraj Hospital: collaborator

Study Sites (1)

Faculty of Medicine Siriraj Hospital

Bangkok Noi, Bangkok, 10700, Thailand

RECRUITING

Related Publications (8)

• Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care. 2019 May 31;23(1):196. doi: 10.1186/s13054-019-2478-6.

  PMID: 31151462 BACKGROUND

• Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21.

  PMID: 28528561 BACKGROUND

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

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

  PMID: 28101605 BACKGROUND

• Ankawi G, Fan W, Pomare Montin D, Lorenzin A, Neri M, Caprara C, de Cal M, Ronco C. A New Series of Sorbent Devices for Multiple Clinical Purposes: Current Evidence and Future Directions. Blood Purif. 2019;47(1-3):94-100. doi: 10.1159/000493523. Epub 2018 Sep 25.

  PMID: 30253409 BACKGROUND

• Elzinga M, Maron BJ, Adelstein RS. Human heart and platelet actins are products of different genes. Science. 1976 Jan 9;191(4222):94-5. doi: 10.1126/science.1246600.

  PMID: 1246600 BACKGROUND

• Koponen T, Karttunen J, Musialowicz T, Pietilainen L, Uusaro A, Lahtinen P. Vasoactive-inotropic score and the prediction of morbidity and mortality after cardiac surgery. Br J Anaesth. 2019 Apr;122(4):428-436. doi: 10.1016/j.bja.2018.12.019. Epub 2019 Feb 18.

  PMID: 30857599 BACKGROUND

• Huang Z, Wang SR, Su W, Liu JY. Removal of humoral mediators and the effect on the survival of septic patients by hemoperfusion with neutral microporous resin column. Ther Apher Dial. 2010 Dec;14(6):596-602. doi: 10.1111/j.1744-9987.2010.00825.x.

  PMID: 21118369 RESULT

MeSH Terms

Conditions

Shock, Septic; Cytokine Release Syndrome; Sepsis

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Ranistha Ratanarat, MD

CONTACT

+66 2419 7767; ranittha@hotmail.com

Nattapat Wongtirawit, MD

CONTACT

+66 2419 7767; n.wongtirawit@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Doctor

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: November 29, 2021
• Study Start: December 15, 2021
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2023
• Last Updated: November 29, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)