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

January 29, 2024 updated by: RWTH Aachen University

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 0.4ml/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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Austria
      • Wien, Austria, 1090
        • Not yet recruiting
        • Medizinische Universität Wien, Klinische Abteilung für Allgemeine Anästhesie und Intensivmedizin
        • Contact:
        • Principal Investigator:
          • Katharina Krenn, Dr. med. univ.
        • Sub-Investigator:
          • Felix Kraft, Dr. med. univ.
  • Germany
      • Aachen, Germany, 52074
        • Recruiting
        • Uniklinik RWTH Aachen, Klinik für Operative Intensivmedizin und Intermediate Care
        • Contact:
        • Principal Investigator:
          • Gernot Marx, Univ.-Prof. Dr. med.
        • Sub-Investigator:
          • Tim-Philipp Simon, PD Dr. med.
      • Bochum, Germany, 44892
        • Not yet recruiting
        • Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Klinik für Anästesiologie, Intensivmedizin und Schmerztherapie
        • Contact:
        • Principal Investigator:
          • Michael Adamzik, Univ. - Prof. Dr. med.
        • Sub-Investigator:
          • Tim Rahmel, PD Dr. med.
      • Dortmund, Germany, 44309
        • Terminated
        • Klinikum Westfalen, Knappschaftskrankenhaus Dortmund, Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie
      • Dresden, Germany, 01307
        • Withdrawn
        • Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie
      • Düsseldorf, Germany, 40225
        • Withdrawn
        • Universitätsklinikum Düsseldorf, Klinik für Anästhesiologie
      • Frankfurt, Germany, 60590
        • Not yet recruiting
        • Universitätklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
        • Contact:
        • Principal Investigator:
          • Kai Zacharowski, Univ.-Prof. Dr. med.
        • Sub-Investigator:
          • Simone Lindau, Dr. med.
      • Freiburg, Germany, 79106
        • Not yet recruiting
        • Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie
        • Contact:
        • Principal Investigator:
          • Stefan Utzolino, Prof. Dr. med.
        • Sub-Investigator:
          • Laura Matuschik, Dr. med.
      • Hamburg, Germany, 20246
        • Not yet recruiting
        • Universitätsklinikum Hamburg-Eppendorf, Zentrum für Anästhesiologie und Intensivmedizin
        • Contact:
        • Principal Investigator:
          • Axel Nierhaus, Dr. med.
        • Sub-Investigator:
          • Stefan Kluge, Prof. Dr. med.
      • Hannover, Germany, 30625
        • Withdrawn
        • Medizinische Hochschule Hannover, Zentrum für Anästhesiologie und Intensivmedizin
      • Heidelberg, Germany, 69120
        • Withdrawn
        • Universitätsklinikum Heidelberg, Anästhesiologische Klinik
      • Magdeburg, Germany, 39130
        • Not yet recruiting
        • Klinikum Magdeburg, Klinik für Intensivmedizin
        • Contact:
        • Principal Investigator:
          • Martin Sauer, Prof. Dr. med. habil.
        • Sub-Investigator:
          • Cornelia Fritz, Dr. med.
      • Mainz, Germany, 55131
        • Withdrawn
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
      • München, Germany, 81377
        • Not yet recruiting
        • Klinikum der Universität München, Klinikum der Universität München, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
        • Contact:
        • Principal Investigator:
          • Markus Albertsmeier, PD Dr. med.
        • Sub-Investigator:
          • Michael Neuberger, Dr. med. Dr. med. univ.
      • Zwickau, Germany, 08060
        • Not yet recruiting
        • Heinrich-Braun-Klinikum gGmbH, Klinik für Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie
        • Contact:
        • Principal Investigator:
          • Udo Gottschaldt, Dr. med.
        • Sub-Investigator:
          • Andreas Reske, Prof. Dr. med.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control arm
Standard of Care treatment
Active Comparator: Verum arm
Standard of Care treatment + Pentaglobin®
Drug: Pentaglobin®/Standard of Care
Standard of Care treatment + Pentaglobin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 was obtained are assigned a score of 10 points.
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death within 28 days
Time Frame: 28 days
Evaluation of death within 28-days.
28 days
Death within 90 days
Time Frame: 90 days
Evaluation of death within 90-days.
90 days
Change in MOF Score from baseline to day 5
Time Frame: 5 days
Change in MOF Score from baseline to day 5.
5 days
Multi-Organ Failure (i.e., > 4 MOF points) on Day 7
Time Frame: 7 days
MOF (i.e., > 4 MOF points) on Day 7 Day 7
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RWTH Aachen University

Collaborators

Biotest

Investigators

  • Principal Investigator: Gernot Marx, Univ.-Prof., RWTH Aachen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 20, 2017

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

October 27, 2017

First Submitted That Met QC Criteria

November 2, 2017

First Posted (Actual)

November 7, 2017

Study Record Updates

Last Update Posted (Estimated)

January 31, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-167

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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