Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock
- Conditions
- Septic Shock
- Interventions
- Device: Therapeutic Plasma Exchange (TPE)
- Registration Number
- NCT05726825
- Lead Sponsor
- Hannover Medical School
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 274
- 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)
- Age < 18 or > 80 years
- Urogenital focus of infection
- Pregnancy
- Heparin-induced thrombocytopenia
- Known reaction against fresh frozen plasma (FFP)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Therapeutic Plasma Exchange (TPE) Therapeutic Plasma Exchange (TPE) 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.
- Primary Outcome Measures
Name Time Method 28-day mortality from randomization up to 28 days following randomization
- Secondary Outcome Measures
Name Time Method Basic Hemodynamics at days 1-7 following randomization includes: Norepinephrine- \[µg/kg/min\], Dobutamine \[µg/kg/min\], Epinephrine- \[µg/kg/min\] and Vasopressin-dose \[U/kg/min\], Vasocative-inotropic (VIS) Score with higher scores indicating higher vasopressor/inotropic support, Mean arterial pressure (MAP, \[mmHg\]), Heart Rate (HR, \[1/min\]), Central venous pressure (CVP, \[mmHg\]) and Central-Venous Oxygen Saturation (ScvO2, \[%\]) at 0 and 12 hrs, d1-7
Organ support free days until day 28 (KEY secondary outcome) from randomization up to 28 days following randomization total days free of invasive ventilation, vasopressors/inotrops and renal replacement therapy (RRT) until day 28
Mean daily Sequential Organ Failure Score (SOFA) score over the first 7 days (KEY secondary outcome) from randomization up to 7 days following randomization Per-patient mean daily SOFA score over the first 7 days, ranging from 0-24 points with higher scores indicating more severe organ dysfunction
Intensive Care unit (ICU) length of stay from randomization until ICU discharge total days in ICU
Hospital length of stay from randomization until hospital discharge total days in hospital
90-day mortality from randomization up to 90 days following randomization Renal function at days 1-7 following randomization and at ICU discharge includes: Presence of Acute kindey injury (AKI), AKI stage (KDIGO definition) stage 1-3 with higher stage indicating worse renal function, Need for Renal Replacement Therapy (RRT), Estimated Glomerular Filtration Rate (eGFR following CKD-EPI equation) \[ml/min\], Fluid intake \[ml/d\], Urine output \[ml/d\], Ultrafiltration and Net daily fluid balance \[ml/d\] at 0 and 12 hrs, d1-7 and at ICU discharge
Respiratory function at days 1-7 following randomization includes: pO2/FiO2, Tidal Volume (VT, \[ml\]), Positive End-Exspiratory Pressure (PEEP, \[cmH2O\]), Peak-Pressure (Ppeak, \[cmH2O\]), Plateau-Pressure (Pplat, \[cmH2O\]), Respiratory Rate (RR, \[1/min\]), Inspiratory Time (Tinsp, \[s\]), Inspiratory-Flow and End-tidal-CO2 (etCO2, \[mmHg\]) at 0 and 12 hrs, d1-7
Extended Hemodynamics at days 1-7 following randomization includes: Cardiac Index (CI, \[l/min/m2\]), Global End-Diastolic Volume Index (GEDI, \[ml/m2\]), Sytemic Vascular Resistance Index (SVRI, \[dyn\*s\*cm-5\*m2\]), Stroke Volume Variation (SVV, \[%\] ), Extravascular Lung Water Index (ELWI, \[ml/kg\]) and Pulmonar Vascular Permeability Index (PVPI) at at 0 and 12 hrs, d1-7
Arterial blood gas analysis at days 1-7 following randomization includes: pH, PCO2 \[mmHg\], HCO3- \[mmol\], PO2 \[mmHg\], Lactate \[mmol/l\] at 0 and 12 hrs, d1-7
Liver Function at days 1-7 following randomization and at ICU discharge includes: Bilirubin, Aspartate aminotransferase (AST, \[U/l\]), Alanine aminotransferase (ALT, \[U/l\]), Alkaline phosphatase (AP, \[U/l\]), Gamma-glutamyl transferase (GGT, \[U/l\]), Cholinesterase (CHE, \[kU/l\]) and Albumin \[g/l\] at 0 and 12 hrs, d1-7 and at ICU discharge
Cardiac function at days 1-7 following randomization and at ICU discharge includes: Creatine kinase (CK, \[U/l\]), Myoglobin \[ug/l\], Troponin T \[ng/l\], NT-proBNP \[ng/l\] at 0 and 12 hrs, d1-7 and at ICU discharge
Secondary infections from randomization until hospital discharge includes: incidence and type of secondary infections until ICU and hospital discharge, incidence of viral (HSV, EBV, CMV) reactivation at d7 and d14
Sepsis associated coagulopathy at days 1-7 following randomization includes: Differential blood count including schistocytes \[%\], Fibrinogen \[g/l\] , D-Dimer \[mg/l\], International Normalized Ratio (INR), Lactate dehydrogenase (LDH, \[U/l\]), Antithrombin-III (AT-III, \[%\]), Protein C \[%\] and International Society on Thrombosis and Hemostasis- Disseminated Intravscular Coagulation Score (ISTH-DIC, \[U/l\]) ranging from 0-8 points with higher values indication more severe DIC at 0 and 12 hrs, d1-7, A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13, \[%\]) and von-Willebrand-Factor Antigen (vWF:Ag,\[IU/l\]) at 0 and 24 hrs
Inflammatory response at days 1-7 following randomization includes: C-reactive protein (CRP, \[mg/l\]), Procalcitonin (PCT, \[ug/l\]), Interleukin-6 (IL-6, \[ng/ml\]), Ferritin \[ug/l\] and Neutrophil/Lymphocyte ratio at 0 and 12 hrs, d1-7
Trial Locations
- Locations (25)
University Hospital Innsbruck
🇦🇹Innsbruck, Austria
University Hospital Vienna
🇦🇹Vienna, Austria
St. Joseph Hospital
🇩🇪Berlin, Germany
University Hospital Berlin Charite
🇩🇪Berlin, Germany
University Hospital Bonn
🇩🇪Bonn, Germany
Hospital Braunschweig
🇩🇪Braunschweig, Germany
Hospital Bremerhaven
🇩🇪Bremerhaven, Germany
Hospital Cologne Meerheim
🇩🇪Cologne, Germany
University Hospital Cologne
🇩🇪Cologne, Germany
University Hospital Erlangen
🇩🇪Erlangen, Germany
University Hospital Essen
🇩🇪Essen, Germany
University Hospital Halle
🇩🇪Halle, Germany
University Hospital Hamburg (UKE)
🇩🇪Hamburg, Germany
Hannover Medical School Anesthesiology
🇩🇪Hannover, Germany
Hannover Medical School Internal Medicine
🇩🇪Hannover, Germany
University Hospital Heidelberg
🇩🇪Heidelberg, Germany
University Hospital Jena
🇩🇪Jena, Germany
University Hospital Kiel
🇩🇪Kiel, Germany
Hospital Magdeburg
🇩🇪Magdeburg, Germany
University Hospital Muenster Anesthesiology
🇩🇪Muenster, Germany
University Hospital Munich (TUM) Anesthesiology
🇩🇪Munich, Germany
University Hospital Munich (TUM) Internal Medicine
🇩🇪Munich, Germany
University Hospital Rostock
🇩🇪Rostock, Germany
University Hospital Bern
🇨🇭Bern, Switzerland
University Hospital Zurich
🇨🇭Zurich, Switzerland