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 (RESTORE I)

A Multi-center Randomized Controlled First in Human Trial to Assess the Feasibility and Preliminary Safety Data of Adjunctive Treatment with the HemoSystem REBOOT in Critically Ill PatientS with Sepsis-induced ImmunOsuppREssion (RESTORE I)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Device: Hemosystem REBOOT

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 Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephanie Sauter, PhD; Phone Number: +41765182096; Email: stephanie.sauter@hemotune.ch

Study Locations

• Switzerland
  • Bern, Switzerland
    • University Hospital Bern Inselspital
    • Contact: Jan Waskowski, MD
  • Zurich, Switzerland
    • University Hospital Zurich
    • Contact: Sascha David, Prof Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; 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.	Device: Hemosystem REBOOT; The HemoSystem REBOOT will selectively remove three mediators largely contributing to sepsis-induced immunosuppression, from extracorporeal circulation based on magnetic beads.; Other Names: extracorporeal blood purification
No Intervention: Standard of care; Best standard of care will be applied to these patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker for sepsis induced immunosuppression (monocytic HLA-DR = mHLA-DR)	Change in mHLA-DR levels during treatment compared to the standard of care arm alone	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)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: hemotune AG
• Investigators: Principal Investigator: Joerg Schefold, Prof, University Hospital Berne, Inselspital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): July 28, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: January 12, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: immunosuppression
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Critical Illness; Shock, Septic
• Other Study ID Numbers: Restore I; HNT001 (Other Identifier: hemotune AG)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No