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NCT Number: NCT05726825

Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock

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.

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Key information

Conditions

Septic Shock Infections Inflammation Multiple Organ Failure Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Shock Shock, Septic Systemic Inflammatory Response Syndrome

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Innsbruck, Innsbruck, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Therapeutic Plasma Exchange (TPE)

Device

The TPE treatment will be initiated within 6 hrs after randomization. Duration of TPE treatment is approximately 120-180 minutes. An additional second TPE can be performed if the patient remains vasopressor dependent ≥ 0.4 ug/kg/min after 24 hours following the first TPE procedure.

Both unfractionated heparin (UFH) and citrate may be used as anticoagulant medication.

To ensure treatment comparability between different patients, we will replace plasma in a fixed ratio of 1.2 x the individual patient's total plasma fluid.

Primary outcomes

  1. 28-day mortality

    Time frame: from randomization up to 28 days following randomization

Secondary outcomes

  1. Mean daily Sequential Organ Failure Score (SOFA) score over the first 7 days (KEY secondary outcome)

    Time frame: 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

  2. Organ support free days until day 28 (KEY secondary outcome)

    Time frame: from randomization up to 28 days following randomization

    total days free of invasive ventilation, vasopressors/inotrops and renal replacement therapy (RRT) until day 28

  3. 90-day mortality

    Time frame: from randomization up to 90 days following randomization

  4. Intensive Care unit (ICU) length of stay

    Time frame: from randomization until ICU discharge

    total days in ICU

  5. Hospital length of stay

    Time frame: from randomization until hospital discharge

    total days in hospital

  6. Basic Hemodynamics

    Time frame: 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

  7. Extended Hemodynamics

    Time frame: 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

  8. Arterial blood gas analysis

    Time frame: at days 1-7 following randomization

    includes: pH, PCO2 [mmHg], HCO3- [mmol], PO2 [mmHg], Lactate [mmol/l] at 0 and 12 hrs, d1-7

  9. Respiratory function

    Time frame: 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

  10. Renal function

    Time frame: 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

  11. Liver Function

    Time frame: 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

  12. Sepsis associated coagulopathy

    Time frame: 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

  13. Inflammatory response

    Time frame: 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

  14. Cardiac function

    Time frame: 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

  15. Secondary infections

    Time frame: 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

Other outcomes

  1. Safety Endpoints

    Time frame: from randomization until day 7 following randomization

    includes: Incidence of bleeding, allergic reactions, Transfusion associated lung injury (TRALI), severe thrombocytopenia (< 5000/µl) and (other) severe adverse events (SAEs)

Study contacts

Contact information is provided by the study sponsor or research team.

Klaus Stahl, PD Dr.

CONTACT

[email protected]

+49 (0)176 1532 8277

Sascha David, Prof. Dr.

CONTACT

[email protected]

+41 44 255 8653

Sponsors and collaborators

Lead sponsor

Hannover Medical School

Other

Registry information

Official study title

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

Acronym: EXCHANGE-2

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Feb 14, 2023
Registry last updated
Mar 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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