First in Human Trial to Assess the Feasibility and Preliminary Safety of Adjunctive Treatment with the HemoSystem REBOOT in Critically Ill Patients with Sepsis-induced Immunosuppression

Not Applicable

Not yet recruiting

• Conditions: Septic Shock
• Interventions: Device: Hemosystem REBOOT

• Registration Number: NCT06258291
• Lead Sponsor: hemotune AG

Brief Summary

The aim of this randomized controlled trial is to restore immune function by selectively removing three mediators largely contributing to sepsis-induced immunosuppression from extracorporeal circulation.

Detailed Description

The treatment safety and the kinetics of specific biomarkers will be assessed to evaluate the selection of the treatment regimen. In a first step, 16 patients will be randomized 1:1 into two arms:

Treatment arm 1: One treatment of 2 hours per day for a maximum of five days or until ICU discharge or death or withdrawal of consent, whichever occurs first.

Control arm: Five consecutive days following the first mHLA-DR measurement post study randomization, or until ICU discharge or death or withdrawal of consent, whichever occurs first

And the end of this treatment phase, it will be decided whether the dosage regimen of HemoSystem REBOOT needs to be adapted and another eight patients have to be enrolled with 2 treatments per day, and a maximum of five treatments.

Study Timeline

• Study First Submitted: 2024-01-12
• Study First Submitted QC: 2024-02-13
• Study First Posted: 2024-02-14
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-14
• Study Start: 2025-09-01
• Primary Completion: 2026-07-28
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Age ≥ 18 years

2. Written informed consent according to national requirements.

3. Hospitalized in ICU or IMC at randomization.

4. Expected length of intensive care unit stay (from randomization) >48 hours.

5. Suspected or confirmed bacterial sepsis.

6. Septic shock diagnosis at any time during ICU/IMC stay according to Sepsis - 3 criteria definition:

   1. an infection (suspected or confirmed);
   2. persisting hypotension requiring any dose of vasopressors (norepinephrine, vasopressin) to maintain a systemic mean blood pressure > 65 mmHg despite adequate fluid resuscitation (minimum of 30 ml/kg crystalloids);
   3. elevated lactate ≥ 2.0 mmol/L with suspected hypoperfusion.

7. Persistent immunosuppression defined as mHLA-DR expression levels < 5600 Ab/cell (Cyto-Chex tubes) in at least two consecutive measurements 20-72 hours apart.

Exclusion criteria:

1. Current ongoing chronic treatment using immunosuppressive biologicals or active lymphocyte therapy (e.g. endoxan, rituximab) or corticosteroid use at a dose > 10 mg/day equivalent of prednisone. However, acute treatment using a maximum dose of hydrocortisone of 200 mg/day for sepsis is allowed.

2. Patient with preexisting known severe immune deficiency (e.g. severe combined immunodeficiency, HIV infection, AIDS).

3. Active or planned extracorporeal membrane oxygenation treatment.

4. Active or planned other extracorporeal blood purification treatments with systems like CytoSorb®, ToraymyxinTM, Gambro Adsorba, etc.

5. Patients post solid-organ transplantation.

6. Known active malignancy (i.e. patients under active anti-malignant treatment).

7. Acute severe burn injury > 20% of the body surface area.

8. Contraindication to use the HemoSystem:

   1. Sensitivity / allergy to HemoSystem components
   2. Body weight < 50 kg
   3. Platelets count < 20,000/µL
   4. History of heparin-induced thrombocytopenia.

9. Females who are known to be pregnant or known to be breastfeeding (b-HCG testing performed in female patients aged < 55 years),

10. Moribund patient with life expectancy < 48h

11. Known history of bleeding disorders or severe coagulopathies (e.g., Hemophilia A, Hemophilia B, Idiopathic Thrombocytopenic Purpura, Von Willebrand Disease types I, II, and III)

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment arm	Hemosystem REBOOT	The REBOOT Hemosystem will be tested in the treatment arm for a maximum of 5 treatments, the treatment will be applied in addition to standard of care alone.

Primary Outcome Measures

Name	Time	Method
Biomarker for sepsis induced immunosuppression (monocytic HLA-DR = mHLA-DR)	pre-procedure immune marker levels compared to post-treatment levels at least 24 hours after last treatment (on average estimated day 6 after treatment start)	Change in mHLA-DR levels during treatment compared to the standard of care arm alone

Secondary Outcome Measures

Name	Time	Method
To assess the total number of organ support free days in intensive and intermediate care unit	until the end of the initial ICU admission (on average day 10 after initial ICU admission)	Difference in total number of organ support free days between treatment arm and standard of care arm
To assess the technical success of in vivo target removal	immediately after last treatment	Technical success rate in treatment arm
To determine all-cause mortality up to 90 days follow-up	through the end of the study (on average 90 days follow up)	Difference in mortality between treatment arm and standard of care arm
To assess vasopressor doses during intensive and intermediate care unit stay	until the end of the initial ICU admission (on average day 10 after initial ICU admission)	To assess the difference in dosing between the treatment arm and standard of care arm
To assess the use of antimicrobial medication	through the end of the study (on average 90 days follow up)	Difference in days on antimicrobials vs days off antimicrobials between treatment arm and standard of care arm
Number of SADEs in treatment arm	through the end of the study (on average 90 days follow up)	SADE rate
Need for organ support therapy (the number of days on organ support in the intensive care unit (index admission) defined by (1) invasive mechanical ventilation, (2) Intermittent or continuous renal replacement therapy, (3) any vasopressor support.	until the end of the initial ICU admission (on average day 10 after initial ICU admission)	Difference between treatment arm and standard of care arm
To assess the change of Sequential Organ Failure Assessment (SOFA) score (ranging from 0 =normal to 4=significantly impaired per category)	through the end of the study (on average 90 days follow up)	Difference in SOFA score between treatment arm and standard of care arm
To evaluate the change in the biomarker (for sepsis-induced immunosuppression) mHLA-DR concentration at various timepoints during ICU stay	at admission to ICU, on the day of first, 2nd, 3rd, 4th, and 5th treatment, and daily up to 72 hours after last treatment.	Difference in immune markers between treatment arm and standard of care arm will be compared

Trial Locations

Locations (2)

University Hospital Zurich; 🇨🇭 Zurich, Switzerland

University Hospital Bern Inselspital; 🇨🇭 Bern, Switzerland