First in Human Trial to Assess the Safety & Efficacy of HemoSystem REBOOT in Patients With Sepsis-induced Immunosuppression

Septic Shock Clinical Trial

— (RESTORE)  

Official title:

A Multi-centre Randomized Controlled Trial to Assess Safety and Efficacy of Adjunctive Treatment With the HemoSystem REBOOT in Critically Ill patientS wiTh Sepsis-induced Immunosuppression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06258291
• Other study ID #: Restore I
• Secondary ID: HNT001
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 15, 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: February 2024
• Source: hemotune AG
• Contact: Stephanie Sauter, PhD
• Phone: +41765182096
• Email: stephanie.sauter[@]hemotune.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study will be divided in two phases: I) Safety and Dose Selection Phase Within a first safety and dose selection phase, the treatment safety and the kinetics of specific biomarkers will be assessed to evaluate the selection of the treatment regimen. In a first step the 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 After confirmation of the safety by an independent DSMB; the study will move into the efficacy phase. II) Efficacy phase Unless the study is stopped for safety reasons, at least 106 patients will be randomized 1:1 into a control arm or the selected treatment arm. An pre-defined interim analysis will be conducted when at least 28 patients in each treatment arm have completed the initial treatment phase. The interim analysis will also include a sample size re-estimation. The results will be reviewed by the independent DSMB, which will make recommendations about safety, early stopping for futility, and sample size re-estimation (which means an increase of the sample size to 180 patients).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 122
• Est. completion date: June 30, 2026
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (judged by independent treating physician).

5. Suspected or confirmed bacterial sepsis (judged by independent treating physician).

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 (according to independent treating physician)

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)

Related Conditions & MeSH terms

• Septic Shock
• Shock, Septic

Intervention

Device:
• Hemosystem REBOOT
The HemoSystem REBOOT will selectively remove three mediators largely contributing to sepsis-induced immunosuppression, from extracorporeal circulation based on magnetic beads.

Locations

Country	Name	City	State
Switzerland	University Hospital Bern Inselspital	Bern
Switzerland	University Hospital Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
hemotune AG

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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.
Secondary	To assess the technical success of in vivo target removal	Technical success rate in treatment arm	immediately after last treatment
Secondary	Number of SADEs in treatment arm	SADE rate	through the end of the study (on average 90 days follow up)