Prospective, Randomized Trial of Personalized Medicine With Pentaglobin® After Surgical Infectious Source Control in Patients With Peritonitis
Overview
- Phase
- Phase 2
- Intervention
- Pentaglobin®/Standard of Care
- Conditions
- Peritonitis
- Sponsor
- RWTH Aachen University
- Enrollment
- 200
- Locations
- 20
- Primary Endpoint
- 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.
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
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.
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 0.4 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.
Investigators
Eligibility Criteria
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.
Exclusion Criteria
- Not provided
Arms & Interventions
Verum arm
Standard of Care treatment + Pentaglobin®
Intervention: Pentaglobin®/Standard of Care
Outcomes
Primary Outcomes
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.
Time Frame: 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 are assigned a score of 10 points.
Secondary Outcomes
- Death within 90 days(90 days)
- Change in MOF Score from baseline to day 5(5 days)
- Multi-Organ Failure (i.e., > 4 MOF points) on day 7(7 days)
- Death within 28 days(28 days)