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

RWTH Aachen University

Status and phase: Enrolling; Phase 2

Conditions: Peritonitis; Septic Shock; Sepsis

Treatments: Drug: Pentaglobin®/Standard of Care

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03334006

2024-513526-27-00 (EU Trial (CTIS) Number)

2016-001788-34 (EudraCT Number)

15-167

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. The patient is diagnosed with secondary or quaternary peritonitis
2. 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).
3. Sepsis and / or septic shock (according to the current sepsis guideline of the German Sepsis Society).
4. SOFA Score ≥ 8
5. The concentration of IL-6 is ≥ 1000 pg / ml
6. Treatment with antibiotics is started within 12 hours of admission to the Intensive Care Unit
7. 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

1. Patients with a life expectancy of less than 90 days due to medical conditions unrelated to peritonitis nor with sepsis and / or septic shock.
2. For female patients: The patient is pregnant or breastfeeding.
3. The patient is a minor (< 18 years of age).
4. The patient has known chronic renal dysfunction requiring dialysis (creatinine ≥ 3.4 mg / dl or creatinine clearance ≤ 30 mL/min/1.73 m²).
5. The patient has acute, primarily non-infectious pancreatitis or mediastinitis.
6. The patient has a BMI > 40.
7. The patient has any contraindication to study drug.
8. The patient has participated in another clinical trial within the last 30 days.
9. The patient is in a dependent or employment relationship with the sponsor or investigator.
10. The patient is institutionalized by court or government order.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Control arm

No Intervention group

Description:

Standard of Care treatment

Verum arm

Active Comparator group

Description:

Standard of Care treatment + Pentaglobin®

Treatment:

Drug: Pentaglobin®/Standard of Care