Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock (EXCHANGE-2)

Hannover Medical School (MHH)

Status: Enrolling

Conditions: Septic Shock

Treatments: Device: Therapeutic Plasma Exchange (TPE)

Study type: Interventional

Funder types: Other

Identifiers

NCT05726825

EXCHANGE-2

Details and patient eligibility

About

Randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of therapeutic plasma exchange in patients with early septic shock.

Full description

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; in septic shock profound circulatory, cellular and metabolic abnormalities are associated with an even higher mortality. Sepsis is a major healthcare problem, affecting millions of individuals around the world each year. Its incidence appears to be rising, and the mortality caused by septic shock in Germany in 2015 remains extraordinarily high (58.8%). It is well known - from the pathophysiological point of view - that these patients do not die from their infection per se but rather from multiple organ failure caused by their own overwhelming host response. This fact is so fundamental that it has been implemented as a key part of the 2016 sepsis definition (SEPSIS-3). Despite tremendous efforts during the last decades, innovative approaches targeting this fundamental hallmark of the disease, thereby reducing organ dysfunction, are lacking. Undoubtedly, there is an unmet need to expand the current standard of care for these patients by a more specific intervention.

The investigators hypothesize that early Therapeutic Plasma Exchange (TPE) in the most severely ill individuals will dampen the injurious maladaptive host response by removing injurious mediators thereby limiting organ dysfunction. The potential impact of this trial is of immense clinical relevance as it evaluates a promising adjunctive treatment option for a patient cohort suffering from an extraordinary high mortality. A positive trial result could truly change the current standard of care (SOC) - that is mostly supportive - of septic shock patients. Of note, there is neither a patent nor a direct commercial interest in such a trial.

Enrollment: 274 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• New onset of septic shock (< 24 hrs), (SEPSIS-3 definition)
• Norepinephrine (NE) dose ≥ 0.4 μg/kg/min ≥ 30 min OR NE ≥ 0.3 μg/kg/min + vasopressin (any dose)
• Established vascular access suitable for plasma exchange independent of study inclusion (due to established indication of RRT, expected need for RRT within the next 48 hours or other medical reasons as assessed by treating physician team)

Exclusion criteria

• Age < 18 or > 80 years
• Urogenital focus of infection
• Pregnancy
• Heparin-induced thrombocytopenia
• Known reaction against fresh frozen plasma (FFP)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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274 participants in 2 patient groups

Therapeutic Plasma Exchange (TPE)

Experimental group

Description:

1 x TPE with donor Fresh Frozen Plasma (FFPs) (1.2 x individual plasma volume) within the first 6 hrs after randomization. A second TPE can be performed if the patient remains vasopressor dependent ≥ 0.4 ug/kg/min within 24 hours after the first intervention.

Treatment:

Device: Therapeutic Plasma Exchange (TPE)

Standard of Care (SOC)

No Intervention group

Description:

Non-interventional standard of care