Overview
The aim of this prospective, randomized, controlled trial is to provide evidence for adjuvant IgGAM treatment with regard to
- Improvement of patient outcomes for peritonitis. Improvement in outcome will be determined by scores such as MOF, SOFA and survival.
- 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.
- In addition, these biomarkers could help to guide a targeted, i.e. "personalized", adjuvant therapy with Pentaglobin® (IgGAM) in the indication of peritonitis.
Description
The aim of this prospective, randomized, controlled trial is to provide evidence for adjuvant IgGAM treatment with regard to
- Improvement of patient outcomes for peritonitis. Improvement in outcome will be determined by scores such as MOF, SOFA and survival.
- 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.
- 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.
Eligibility
Inclusion Criteria:
- 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