Randomized, Prospective, Multicenter, Open-label, Controlled, Parallel-group Trial Investigating the Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock - 2
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Septic Shock
- Sponsor
- Hannover Medical School
- Enrollment
- 274
- Locations
- 25
- Primary Endpoint
- 28-day mortality
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed 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.
Investigators
Eligibility Criteria
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)
Outcomes
Primary Outcomes
28-day mortality
Time Frame: from randomization up to 28 days following randomization
Secondary Outcomes
- Basic Hemodynamics(at days 1-7 following randomization)
- Organ support free days until day 28 (KEY secondary outcome)(from randomization up to 28 days following randomization)
- Intensive Care unit (ICU) length of stay(from randomization until ICU discharge)
- Mean daily Sequential Organ Failure Score (SOFA) score over the first 7 days (KEY secondary outcome)(from randomization up to 7 days following randomization)
- Hospital length of stay(from randomization until hospital discharge)
- 90-day mortality(from randomization up to 90 days following randomization)
- Renal function(at days 1-7 following randomization and at ICU discharge)
- Respiratory function(at days 1-7 following randomization)
- Extended Hemodynamics(at days 1-7 following randomization)
- Arterial blood gas analysis(at days 1-7 following randomization)
- Liver Function(at days 1-7 following randomization and at ICU discharge)
- Cardiac function(at days 1-7 following randomization and at ICU discharge)
- Secondary infections(from randomization until hospital discharge)
- Sepsis associated coagulopathy(at days 1-7 following randomization)
- Inflammatory response(at days 1-7 following randomization)