Prospective, Randomized Trial of Personalized Medicine With Pentaglobin® After Surgical Infectious Source Control in Patients With Peritonitis
- Conditions
- Septic ShockPeritonitisSepsis
- Interventions
- Drug: Pentaglobin®/Standard of Care
- Registration Number
- NCT03334006
- Lead Sponsor
- RWTH Aachen University
- Brief Summary
The aim of this prospective, randomized, controlled trial is to provide evidence for adjuvant IgGAM treatment with regard to
1. Improvement of patient outcomes for peritonitis. Improvement in outcome will be determined by scores such as MOF, SOFA and survival.
2. Identification of biomarkers (including immunoglobulin levels, HLA-DR, Nf-kB1 and other immunological biomarkers) to identify patient subpopulations that benefit most from IgGAM treatment. These patients will form the basis for a further randomized, controlled, double-blind Phase III trial (RCT) to demonstrate the benefit of this treatment.
3. In addition, these biomarkers could help to guide a targeted, i.e. "personalized", adjuvant therapy with Pentaglobin® (IgGAM) in the indication of peritonitis.
- Detailed Description
The aim of this prospective, randomized, controlled trial is to provide evidence for adjuvant IgGAM treatment with regard to
1. Improvement of patient outcomes for peritonitis. Improvement in outcome will be determined by scores such as MOF, SOFA and survival.
2. Identification of biomarkers (including immunoglobulin levels, HLA-DR, Nf-kB1 and other immunological biomarkers) to identify patient subpopulations that benefit most from IgGAM treatment. These patients will form the basis for a further randomized, controlled, double-blind Phase III trial (RCT) to demonstrate the benefit of this treatment.
3. In addition, these biomarkers could help to guide a targeted, i.e. "personalized", adjuvant therapy with Pentaglobin® (IgGAM) in the indication of peritonitis.
The control group receives Standard-of-Care treatment. The intervention group is additionally treated with IgGAM (Pentaglobin®) as an add-on treatment to Standard-of-Care.
Pentaglobin® is administered by continuous intravenous infusion over a period of 5 days of 0.4ml/kg body weight/hour until the total dose of 7mL/kg body weight/day is reached.
Primary outcome: Change in Multiple Organ Failure (MOF) score (measured in lung, heart, kidney, liver, blood) from baseline to day 7 after surgical infectious source control in the context of peritonitis.
The MOF score is determined in the morning. The following score points are distributed per organ: Normal organ function: 0 score points; organ dysfunction: 1 score point; single organ failure: 2 score points. A score \> 4 in the sum of the 5 organs indicates multiple organ failure. Patients who died before the MOF score was obtained are assigned a score of 10 score points.
Secondary outcome:
* Death within 28 days
* Death within 90 days
* Change in MOF score from baseline to day 5
* Multi-organ Failure ( \> 4 MOF score points on day 7)
Exploratory objectives:
* Effects of Pentaglobin® therapy on the SOFA score (determined in the organs lung, CNS, circulation, liver, coagulation and kidney).
* Interaction of the biomarkers "NF-kB1" (steady), "CRP (≥ 70 mg/L), IgA (\< 150 mg/dl), IgG (\< 300 mg/dl), IgM (\< 35 mg/dl) and HLA-DR expression (≤ 8,000 molecules per monocyte) with therapy in terms of change in MOF score from baseline to days 5 and 7 and death within 28 and 90 days.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- The patient is diagnosed with secondary or quaternary peritonitis
- The time of the surgical infectious source control is within 6 hours of indication (defined as date and time of registration for surgical or minimal invasive procedure).
- Sepsis and / or septic shock (according to the current sepsis guideline of the German Sepsis Society).
- SOFA Score ≥ 8
- The concentration of IL-6 is ≥ 1000 pg / ml
- Treatment with antibiotics is started within 12 hours of admission to the Intensive Care Unit
- The informed consent form has been signed by the patient and / or by his legal representative (such as his spouse, an health care proxy authorized or a legal representative) or by a consultant physician
Exclusion criteria
- Patients with a life expectancy of less than 90 days due to medical conditions unrelated to peritonitis nor with sepsis and / or septic shock.
- For female patients : The patient is pregnant or breastfeeding
- The patient is a minor (< 18 years of age).
- The patient has known chronic renal dysfunction requiring dialysis (creatinine ≥ 3.4 mg / dl or creatinine clearance ≤ 30 mL / min / 1.73 m2).
- The patient has acute, primarily non-infectious pancreatitis or mediastinitis
- The patient has a BMI> 40.
- The patient has any contraindication to study drug.
- The patient has participated in another clinical trial within the last 30 days.
- The patient is in a dependent or employment relationship with the sponsor or investigator.
- The patient is institutionalized by court or government order
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Verum arm Pentaglobin®/Standard of Care Standard of Care treatment + Pentaglobin®
- Primary Outcome Measures
Name Time Method Change in Multiple Organ Failure (MOF) score (measured in lung, heart, kidney, liver, blood) from baseline to day 7 after surgical infectious source control in the context of peritonitis. 7 days The MOF score is determined in the morning. The following points are distributed per organ: Normal organ function: 0 points; organ dysfunction: 1 point; single organ failure: 2 points. A score \> 4 in the sum of the 5 organs indicates multiple organ failure. Patients who died before the MOF score was obtained are assigned a score of 10 points.
- Secondary Outcome Measures
Name Time Method Change in MOF Score from baseline to day 5 5 days Change in MOF Score from baseline to day 5.
Death within 90 days 90 days Evaluation of death within 90-days.
Multi-Organ Failure (i.e., > 4 MOF points) on Day 7 7 days MOF (i.e., \> 4 MOF points) on Day 7 Day 7
Death within 28 days 28 days Evaluation of death within 28-days.
Trial Locations
- Locations (19)
Medizinische Universität Wien, Klinische Abteilung für Allgemeine Anästhesie und Intensivmedizin
🇦🇹Wien, Austria
Universitätsklinikum Tübingen, Universitätsklinik für Anästhesiologie und Intensivmedizin
🇩🇪Tübingen, Baden-Württemberg, Germany
Universitätsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin
🇩🇪Essen, Nordrhein-Westfalen, Germany
Uniklinik RWTH Aachen, Klinik für Operative Intensivmedizin und Intermediate Care
🇩🇪Aachen, Germany
Charité - Universitätsmedizin Berlin, Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin
🇩🇪Berlin, Germany
Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Klinik für Anästesiologie, Intensivmedizin und Schmerztherapie
🇩🇪Bochum, Germany
Klinikum Westfalen, Knappschaftskrankenhaus Dortmund, Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie
🇩🇪Dortmund, Germany
Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie
🇩🇪Dresden, Germany
Universitätsklinikum Düsseldorf, Klinik für Anästhesiologie
🇩🇪Düsseldorf, Germany
Universitätklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
🇩🇪Frankfurt, Germany
Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie
🇩🇪Freiburg, Germany
Universitätsklinikum Hamburg-Eppendorf, Zentrum für Anästhesiologie und Intensivmedizin
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover, Zentrum für Anästhesiologie und Intensivmedizin
🇩🇪Hannover, Germany
Universitätsklinikum Heidelberg, Anästhesiologische Klinik
🇩🇪Heidelberg, Germany
Klinikum Magdeburg, Klinik für Intensivmedizin
🇩🇪Magdeburg, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
🇩🇪Mainz, Germany
Klinikum der Universität München, Klinikum der Universität München, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
🇩🇪München, Germany
Klinikum Nürnberg, Klinik für Anästhesiologie und operative Intensivmedizin
🇩🇪Nürnberg, Germany
Heinrich-Braun-Klinikum gGmbH, Klinik für Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie
🇩🇪Zwickau, Germany