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)

hemotune

Status: Not yet enrolling

Conditions: Septic Shock

Treatments: Device: Hemosystem REBOOT

Study type: Interventional

Funder types: Industry

Identifiers

NCT06258291

Restore I

HNT001 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

16 participants in 2 patient groups

Treatment arm

Experimental group

Description:

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.

Treatment:

Device: Hemosystem REBOOT

Standard of care

No Intervention group

Description:

Best standard of care will be applied to these patients.