Clinical trial NCT06258291: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Septic Shock
Keywords: immunosuppression
Lead sponsor: hemotune AG
Sponsor class: INDUSTRY
First posted: 2024-02-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled trial: treatment in addition to standard of care versus standard of care alone
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Biomarker for sepsis induced immunosuppression (monocytic HLA-DR = mHLA-DR)
timeFrame: 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 outcomes:
measure: To determine all-cause mortality up to 90 days follow-up
timeFrame: through the end of the study (on average 90 days follow up)
measure: 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.
timeFrame: until the end of the initial ICU admission (on average day 10 after initial ICU admission)
measure: To assess the total number of organ support free days in intensive and intermediate care unit
timeFrame: until the end of the initial ICU admission (on average day 10 after initial ICU admission)
measure: To assess the change of Sequential Organ Failure Assessment (SOFA) score (ranging from 0 =normal to 4=significantly impaired per category)
timeFrame: through the end of the study (on average 90 days follow up)
measure: To assess vasopressor doses during intensive and intermediate care unit stay
timeFrame: until the end of the initial ICU admission (on average day 10 after initial ICU admission)
measure: To assess the use of antimicrobial medication
timeFrame: through the end of the study (on average 90 days follow up)
measure: To evaluate the change in the biomarker (for sepsis-induced immunosuppression) mHLA-DR concentration at various timepoints during ICU stay
timeFrame: at admission to ICU, on the day of first, 2nd, 3rd, 4th, and 5th treatment, and daily up to 72 hours after last treatment.
measure: To assess the technical success of in vivo target removal
timeFrame: immediately after last treatment
measure: Number of SADEs in treatment arm
timeFrame: through the end of the study (on average 90 days follow up)
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital Bern Inselspital
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University Hospital Berne, Inselspital
name: Joerg Schefold, Prof
role: PRINCIPAL_INVESTIGATOR
References: