Recruiting
Study Start: November, 2017
Study Completion: March, 2028
NCT03334006

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

Keywords:
Peritonitis
Sepsis
Septic shock

Brief Summary

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.

01
Pentaglobin®/Standard of Care
Drug
Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Interventional Model Description

The control group receives a Standard-of-Care treatment. The intervention group is additionally treated with IgGAM (Pentaglobin®) as an add-on treatment to Standard-of-Care.

The preparation to be provided contains (per ml solution) 50 mg human plasma proteins, of which ≥ 95 % are immunoglobulins: IgM 6 mg, IgA 6 mg and IgG 38 mg. The IgG subclass distribution is IgG1 ~ 63 %, IgG2 ~ 26 %, IgG3 ~ 4 %, IgG4 ~ 7 %.

Pentaglobin® is administered by continuous intravenous infusion over a period of 5 day of 0.4 ml/kg body weight/hour until the total dose of 7 ml/kg body weight/day is reached.

Masking

None (Open Label)

No Intervention: Control arm

Standard of Care treatment

Active Comparator: Verum arm

Standard of Care treatment + Pentaglobin®

  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

  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.

Primary Outcome Measures

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 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.

7 days

Secondary Outcome Measures

Death within 28 days

Evaluation of death within 28-days.

28 days

Death within 90 days

Evaluation of death within 90-days.

90 days

Change in MOF Score from baseline to day 5

Change in MOF Score from baseline to day 5.

5 days

Multi-Organ Failure (i.e., > 4 MOF points) on day 7

MOF (i.e., > 4 MOF points) on day 7.

7 days

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