Biological Effects of Hemoadsorption in Septic Shock

NCT07715110 | Not Yet Recruiting

• 2 other identifiers: Bio-HA380Approved by sponsor
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

Septic shock is the most severe form of sepsis and continues to carry an in-hospital mortality of between 30% and 50% despite advances in compliance with the Surviving Sepsis Campaign care bundles. The pathophysiology of septic shock is dominated by an uncontrolled immuno-inflammatory response with massive release of mediators, pro- and anti-inflammatory cytokines5, DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns), producing vasoplegia, endothelial dysfunction, glycocalyx damage and, in many patients, a subsequent immunoparalysis phase that increases the risk of nosocomial infections and late mortality. Endothelial damage and glycocalyx degradation are central elements in the pathophysiology of septic shock. The endothelial glycocalyx, a layer of proteoglycans and glycosaminoglycans approximately 0.5 µm thick on the luminal surface of the endothelium, regulates vascular permeability, leukocyte adhesion and the inflammatory response. During sepsis, the release of metalloproteinases, heparanase and other inflammatory mediators causes the shedding of syndecan-1, heparan sulfate and other glycocalyx molecules into the circulation. This process is associated with increased capillary permeability, interstitial edema, third-space fluid leakage, and progression to multiorgan failure. Elevated plasma syndecan-1 levels correlate with greater severity of septic shock, development of acute respiratory distress syndrome (ARDS), extrapulmonary organ dysfunction, and mortality. In parallel, the release of angiopoietin-2 by activated endothelial cells antagonizes Tie2 signaling, destabilizes the endothelial barrier and amplifies vascular dysfunction. Selective modulation of the immune response through extracorporeal adsorption of medium-sized mediators (5-60 kDa) is an adjunctive strategy whose biological rationale is well established and whose hemodynamic effect has been described by multiple authors. The HA380 HA cartridge (Jafron Biomedical), specifically, uses a synthetic neutral macroporous polymer resin with high affinity for cytokines in the 10-60 kDa range, especially IL-6, TNF-α, IL-8 and IL-10. The device is connected to an extracorporeal therapy circuit (in this protocol, always integrated into a continuous renal replacement therapy \[CRRT\] circuit) and operates for 4-6 hours per cartridge. Removal of proinflammatory cytokines (IL-6, TNF-α, IL-8) with HA380 also aims to reduce their effect on endothelial damage, and recent studies with other cytokine adsorbents have demonstrated the ability to remove circulating angiopoietin-2. Although the specific literature on the effect of HA380 on recovery of glycocalyx integrity is limited, reducing the burden of cytokines and endotoxic mediators could attenuate the glycocalyx degradation cascade and contribute to the hemodynamic stabilization observed in clinical studies. This mechanism provides an additional biological rationale for assessing biomarkers of endothelial dysfunction (angiopoietin-2, syndecan-1, soluble thrombomodulin) as secondary variables in the present study. Within the spectrum of septic shock, this protocol distinguishes two clinically and biologically relevant severity strata: 1) established septic shock as per Sepsis-3 criteria who, despite requiring vasopressor support and showing hyperlactatemia, do not meet the thresholds of refractoriness. 2) refractory septic shock, a particularly severe subgroup in which standard resuscitation measures-guided fluid therapy, vasopressors, source control, early antibiotic therapy, and hydrocortisone-are insufficient to reverse tissue hypoperfusion and progressive organ dysfunction. Primary objective To establish whether HA380 hemoadsorption yields a more desirable overall outcome than concurrent standard of care, within each severity stratum, using a pre-specified hierarchical ordinal DOOR endpoint.

Conditions

Septic Shock, Vasopressor Resistance; Multiple Organ Dysfunction; Sepsis; Hemoperfusion; Hemoadsorption

Keywords

Randomized; Hemoadsorption; Sepsis; Septic shock; Refractory septic shock; Multiple Organ dysfunction

Outcome Measures

Primary Outcomes (1)

• A more desirable overall outcome category in a pre-specified hierarchical ordinal varibles system ("DOOR"; Evans 2015; Pocock 2012).

  To establish whether HA380 hemoadsorption yields a more desirable overall outcome than concurrent standard of care, within each severity stratum, using a pre-specified hierarchical ordinal DOOR endpoint Level and Definition (assessed within each severity stratum) 5. (most desirable): Alive at day 30 + relevant decrease in all 4 components (IL-6, VIS, SOFA-2, lactate)\* at T6 4. Alive at D30 + relevant decrease in 3 of the 4 components at T6 3. Alive at D30 + relevant decrease in 2 of the 4 components at T6 2. Alive at D30 + decrease in 0-1 of the 4 components at T6 1. (least desirable): Death by D30, irrespective of any biological change \* IL-6, reduction ≥ 30% from T0; VIS, any reduction (\> 0) from T0; SOFA-2, reduction ≥ 2 points from T0; and serum lactate, a value \< 2 mmol/L at T6 or a reduction ≥ 10% from T0. A component that cannot be evaluated in a day-30 survivor because of a missing T6 measurement is conservatively counted as 'no decrease'

  30 days

Secondary Outcomes (2)

• Biological endpoints

  72 hours

• Exploratory physiological variables

  72 hours

Study Arms (3)

Control

NO INTERVENTION

Standard of care (Surviving Sepsis Campaign) without hemoadsorption therapy

Septic Shock

EXPERIMENTAL

Septic shock meeting Sepsis-3 definition

Device: Hemoadsorption cartridge

Refractory Septic shock

EXPERIMENTAL

Refractory septic shock meeting SEMICYUC and ESICM/SCCM Delphi consensus definitions

Device: Hemoadsorption cartridge

Interventions

Hemoadsorption cartridge DEVICE

Insertion of a resin-based hemoadsorption cartridge into a continuous renal replacement therapy circuit.

Refractory Septic shock; Septic Shock

Eligibility Criteria

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

You may qualify if:

• All of the following:
• Age ≥ 18 years.
• Diagnosis of septic shock per Sepsis-3, with an identified or highly probable infectious focus.
• Meeting the operational definition of one of the two severity strata (SS or RSS) detailed in 6.1.
• Onset of septic shock within the last 24 hours (applied identically to both strata).
• Large-bore vascular access.
• Informed consent signed by the legal representative.

You may not qualify if:

• Decision to limit life-sustaining therapy made or anticipated within the next 48 hours.
• Absolute contraindication to anticoagulation with heparin and citrate.
• Predominant non-septic shock (hemorrhagic, primary cardiogenic, obstructive).
• Ongoing pregnancy.
• Platelet count \< 20,000/µL.
• Significant pharmacological immunosuppression: chronic corticosteroids at doses \> 20 mg/day prednisone equivalent, biologics within the last 6 months, cytotoxic chemotherapy within the last 4 weeks.
• Solid organ or hematopoietic stem cell transplantation.
• Concurrent participation in another clinical trial.

Sponsors & Collaborators

• Miguel Sanchez Garcia: lead

Study Sites (2)

Ervigio Corral-Torres

Madrid, Es-Md, 28040, Spain

Location

Hospital Clínico San Carlos

Madrid, Es-Md, 28040, Spain

Location

Related Publications (46)

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MeSH Terms

Conditions

Shock, Septic; Sepsis

Condition Hierarchy (Ancestors)

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

Study Officials

• Fernando Martínez-Sagasti, MD, PhD

  Hospial Clinico San Carlos

  STUDY CHAIR

Central Study Contacts

Miguel Sanchez-Garcia

CONTACT

+34658762739; miguelsanchez.hcsc@gmail.com

Belen De la Hera Hernanz, PhD

CONTACT

+34650624550; belenhhernanz@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Emeritus Director Critical Care Department

Model Details: Two parallel pilot clinical trials, single-center, open-label, parallel-group, proof-of-concept, sharing one protocol; patients are stratified by shock severity into a septic shock (SS) stratum and a refractory septic shock (RSS) stratum, with independent 1:1 randomization to hemoadsorption or standard of care within each stratum.

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): January 7, 2027
• Primary Completion (Estimated): January 7, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: after publication of main study results. no end date
• Access Criteria: contact corresponding author

Locations

ES (2)