Personalised Medicine With IgGAM Compared With Standard of Care for Treatment of Peritonitis After Infectious Source Control (the PEPPER Trial)
Study Details
Study Description
Brief Summary
The purpose of this study is to test the adjuvant Immuneglobulins G, A and M (IgGAM) treatment for:
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An improvement of the outcome for the patient's peritonitis. This will be investigated by using scores such as the multiple organ failure (MOF) and Sequential Organ Failure Assessment (SOFA) scores as well as survival data.
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Identification of biomarkers [Ig level, procalcitonin (PCT), interleukin-6 (IL 6), Human Leukocyte Antigen - antigen D Related (HLA DR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF kB1), adrenomedullin (ADM), pathogen spectrum], to identify patient subpopulations that profit most from treatment with IgGAM. Such patients will comprise the basis for a further study, which will be a randomised, controlled, double-blind trial (RCT) to demonstrate the value of this treatment.
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Furthermore, these biomarkers are expected to help with developing a "personalised" adjuvant therapy with IgGAM in the indication of peritonitis.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
The purpose of this study is to test the adjuvant IgGAM treatment for:
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An improvement of the outcome for the patient's peritonitis. This will be investigated by using scores such as the multiple organ failure and SOFA scores as well as survival data.
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Identification of biomarkers (Ig level, PCT, IL 6, HLA DR, Nf kB1, ADM, pathogen spectrum), to identify patient subpopulations that profit most from treatment with IgGAM. Such patients will comprise the basis for a further study, which will be a randomised, controlled, double-blind trial (RCT) to demonstrate the value of this treatment.
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Furthermore, these biomarkers are expected to help with developing a "personalised" adjuvant therapy with IgGAM in the indication of peritonitis.
The control group will receive standard-of-care treatment, i.e., the IgGAM is an add-on treatment in this study.
The active study treatment is IgGAM (Pentaglobin®). IgGAM is administered by continuous infusion over 5 days at a dose level of 0.4 ml per kg body weight per hour, until a total dose of 7 ml/kg on that day has been reached; administration will then be stopped and recommenced on the following day, until administration has been completed for 5 consecutive days.
Primary target variable The relative number of patients whose MOF score improves by 0.8 points on Day 7 (i.e., percentage of 'responders'). The primary analysis will be performed with the per protocol population (see below).
The MOF score is determined in the morning, with the following scoring for each organ (lungs, heart, kidneys, liver, blood): normal function, 0; dysfunction, 1; individual organ failure, 2. An aggregate score greater than 4 implies multi-organ failure. Patients who die will be assigned the maximum score of 10 and will be included in the population assessment.
Secondary target variables
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Overall 28-day survival,
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Overall 90-day survival,
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MOF score on Day 5,
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Relative number of patients with MOF (i.e., > 4 MOF points) on Day 7. Additional study variables
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Time course of the biomarkers (PCT, IL 6, HLA DR, ADM, Immuneglobulins M, G, A), the SOFA score, the Mannheim Peritonitis Index, the surrogate variables for organ dysfunction and survival according to Heyland et al. 2011 and vital signs.
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Influence of the biomarkers NF kB1, ADM and pathogen spectrum upon the outcome for the patient.
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Comparison of the MOF score with other scores, such as the SOFA score, for assessment of organ dysfunction.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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No Intervention: A: Control group Standard of Care |
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Active Comparator: B: Pentaglobin® Standard of Care + Pentaglobin® |
Drug: Pentaglobin®
Standard of Care + Pentaglobin®
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Outcome Measures
Primary Outcome Measures
- Relative number of patients whose MOF score improves by 0.8 points on Day 7 (i.e., percentage of 'responders') [%] [7 days]
The relative number of patients whose MOF score improves by 0.8 points on Day 7 (i.e., percentage of 'responders'). The MOF score is determined in the morning, with the following scoring for each organ (lungs, heart, kidneys, liver, blood): normal function, 0; dysfunction, 1; individual organ failure, 2. An aggregate score greater than 4 implies multi-organ failure. Patients who die will be assigned the maximum score of 10 and will be included in the population assessment. Day 7
Secondary Outcome Measures
- Number of survivers on day 28 [-] [28 days]
Evaluation of the Overall 28-day survival. Day 28
- Number of survivers on day 90 [-] [90 days]
Evaluation of the Overall 90-day survival. Day 90
- MOF Score on day 5 [-] [5 days]
MOF Score on day 5 Day 5
- Relative number of patients with MOF (i.e., > 4 MOF points) on Day 7 [%] [7 days]
Relative number of patients with MOF (i.e., > 4 MOF points) on Day 7 [%] Day 7
Eligibility Criteria
Criteria
Inclusion Criteria:
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Peritonitis
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The time of the surgical infectious source control must have been within 6 h after the indication (defined as the time of the registration of the surgical procedure/ minimal invasive surgery)
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Sepsis and septic shock (according to the current Sepsis Guideline)
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SOFA Score ≥ 8
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IL-6 ≥ 1000 pg / ml
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Start of therapy with antibiotics and IgGAM (Pentaglobin) within 12 hours after admission to the ICU
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Signed informed consent by the patient himself or by his legal representative, such as a court-appointed supervisor or by an authorized proxy authorized representative or by a consultant
Exclusion criteria
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Patients with a life expectancy of less than 90 days due to medical conditions that are not associated with postoperative peritonitis or with sepsis / septic shock
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Pregnant, breastfeeding women
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Minors (< 18 years)
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Patients with a known dialysis-requiring chronic renal function (creatinine ≥ 3.4 mg / dl or creatinine clearance ≤ 30 mL / min / 1.73 m2)
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Patients with acute, primary non-infectious pancreatitis or mediastinitis
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BMI> 40
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Patients with a contraindication to study medication
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Participate in another medication study within the last 30 days
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Persons who are in a relationship of dependency or employment relationship with the sponsor or auditor
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Persons who are placed in an institution on a judicial or administrative order
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | LKH-Univ. Klinikum Graz | Graz | Austria | 8020 | |
2 | Medizinische Universität Wien | Wien | Austria | 1090 | |
3 | University Hospital Aachen | Aachen | Germany | 52074 | |
4 | Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH | Bochum | Germany | 44892 | |
5 | Klinikum Westfalen, Knappschaftskrankenhaus Dortmund | Dortmund | Germany | 44309 | |
6 | Universitätsklinikum Carl Gustav Carus | Dresden | Germany | 01307 | |
7 | Universitätsklinikum Frankfurt | Frankfurt | Germany | 60590 | |
8 | Universitätsklinikum Hamburg-Eppendorf | Hamburg | Germany | 20246 | |
9 | Medizinische Hochschule Hannover | Hannover | Germany | 30625 | |
10 | Universitätsklinikum Heidelberg | Heidelberg | Germany | 69120 | |
11 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Mainz | Germany | 55131 | |
12 | Klinikum der Universität München | München | Germany | 81377 |
Sponsors and Collaborators
- RWTH Aachen University
- Biotest
Investigators
- Principal Investigator: Gernot Marx, Univ.-Prof., RWTH Aachen University
Study Documents (Full-Text)
None provided.More Information
Publications
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