Prospective, Randomized Trial of Personalized Medicine With Pentaglobin® After Surgical Infectious Source Control in Patients With Peritonitis

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 0.4 ml/kg body weight/hour until the total dose of 7 ml/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 (< 700 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.

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.