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Personalised Medicine With IgGAM Compared With Standard of Care for Treatment of Peritonitis After Infectious Source Control (the PEPPER Trial) (PEPPER)

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ClinicalTrials.gov Identifier: NCT03334006
Recruitment Status : Suspended (Due to safety-relevant aspects with regard to internal processes of the sponsor)
First Posted : November 7, 2017
Last Update Posted : January 23, 2020
Sponsor:
Collaborator:
Biotest
Information provided by (Responsible Party):
RWTH Aachen University

Brief Summary:

The purpose of this study is to test the adjuvant Immuneglobulins G, A and M (IgGAM) treatment for:

  1. An improvement of the outcome for the patient's peritonitis. This will be investigated by using scores such as the multiple organ failure (MOF) and Sequential Organ Failure Assessment (SOFA) scores as well as survival data.
  2. Identification of biomarkers [Ig level, procalcitonin (PCT), interleukin-6 (IL 6), Human Leukocyte Antigen - antigen D Related (HLA DR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF kB1), adrenomedullin (ADM), pathogen spectrum], to identify patient subpopulations that profit most from treatment with IgGAM. Such patients will comprise the basis for a further study, which will be a randomised, controlled, double-blind trial (RCT) to demonstrate the value of this treatment.
  3. Furthermore, these biomarkers are expected to help with developing a "personalised" adjuvant therapy with IgGAM in the indication of peritonitis.

Condition or disease Intervention/treatment Phase
Peritonitis Sepsis Drug: Pentaglobin® Phase 2

Detailed Description:

The purpose of this study is to test the adjuvant IgGAM treatment for:

  1. An improvement of the outcome for the patient's peritonitis. This will be investigated by using scores such as the multiple organ failure and SOFA scores as well as survival data.
  2. Identification of biomarkers (Ig level, PCT, IL 6, HLA DR, Nf kB1, ADM, pathogen spectrum), to identify patient subpopulations that profit most from treatment with IgGAM. Such patients will comprise the basis for a further study, which will be a randomised, controlled, double-blind trial (RCT) to demonstrate the value of this treatment.
  3. Furthermore, these biomarkers are expected to help with developing a "personalised" adjuvant therapy with IgGAM in the indication of peritonitis.

The control group will receive standard-of-care treatment, i.e., the IgGAM is an add-on treatment in this study.

The active study treatment is IgGAM (Pentaglobin®). IgGAM is administered by continuous infusion over 5 days at a dose level of 0.4 ml per kg body weight per hour, until a total dose of 7 ml/kg on that day has been reached; administration will then be stopped and recommenced on the following day, until administration has been completed for 5 consecutive days.

Primary target variable The relative number of patients whose MOF score improves by 0.8 points on Day 7 (i.e., percentage of 'responders'). The primary analysis will be performed with the per protocol population (see below).

The MOF score is determined in the morning, with the following scoring for each organ (lungs, heart, kidneys, liver, blood): normal function, 0; dysfunction, 1; individual organ failure, 2. An aggregate score greater than 4 implies multi-organ failure. Patients who die will be assigned the maximum score of 10 and will be included in the population assessment.

Secondary target variables

  • Overall 28-day survival,
  • Overall 90-day survival,
  • MOF score on Day 5,
  • Relative number of patients with MOF (i.e., > 4 MOF points) on Day 7. Additional study variables
  • Time course of the biomarkers (PCT, IL 6, HLA DR, ADM, Immuneglobulins M, G, A), the SOFA score, the Mannheim Peritonitis Index, the surrogate variables for organ dysfunction and survival according to Heyland et al. 2011 and vital signs.
  • Influence of the biomarkers NF kB1, ADM and pathogen spectrum upon the outcome for the patient.
  • Comparison of the MOF score with other scores, such as the SOFA score, for assessment of organ dysfunction.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The control group will receive standard-of-care treatment, i.e., the IgGAM is an add-on treatment in this study.

The active study treatment is IgGAM (Pentaglobin®). 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%. IgGAM is administered by continuous infusion over 5 days at a dose level of 0.4 ml per kg body weight per hour, until a total dose of 7 ml/kg on that day has been reached; administration will then be stopped and recommenced on the following day, until administration has been completed for 5 consecutive days.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Personalised Medicine With IgGAM Compared With Standard of Care for Treatment of Peritonitis After Infectious Source Control (the PEPPER Trial): a Randomised, Controlled Trial
Actual Study Start Date : November 20, 2017
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
No Intervention: A: Control group
Standard of Care
Active Comparator: B: Pentaglobin®
Standard of Care + Pentaglobin®
Drug: Pentaglobin®
Standard of Care + Pentaglobin®




Primary Outcome Measures :
  1. Relative number of patients whose MOF score improves by 0.8 points on Day 7 (i.e., percentage of 'responders') [%] [ Time Frame: 7 days ]

    The relative number of patients whose MOF score improves by 0.8 points on Day 7 (i.e., percentage of 'responders').

    The MOF score is determined in the morning, with the following scoring for each organ (lungs, heart, kidneys, liver, blood): normal function, 0; dysfunction, 1; individual organ failure, 2. An aggregate score greater than 4 implies multi-organ failure. Patients who die will be assigned the maximum score of 10 and will be included in the population assessment.

    Day 7



Secondary Outcome Measures :
  1. Number of survivers on day 28 [-] [ Time Frame: 28 days ]

    Evaluation of the Overall 28-day survival.

    Day 28


  2. Number of survivers on day 90 [-] [ Time Frame: 90 days ]

    Evaluation of the Overall 90-day survival.

    Day 90


  3. MOF Score on day 5 [-] [ Time Frame: 5 days ]

    MOF Score on day 5

    Day 5


  4. Relative number of patients with MOF (i.e., > 4 MOF points) on Day 7 [%] [ Time Frame: 7 days ]

    Relative number of patients with MOF (i.e., > 4 MOF points) on Day 7 [%]

    Day 7




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Peritonitis
  2. The time of the surgical infectious source control must have been within 6 h after the indication (defined as the time of the registration of the surgical procedure/ minimal invasive surgery)
  3. Sepsis and septic shock (according to the current Sepsis Guideline)
  4. SOFA Score ≥ 8
  5. IL-6 ≥ 1000 pg / ml
  6. Start of therapy with antibiotics and IgGAM (Pentaglobin) within 12 hours after admission to the ICU
  7. Signed informed consent by the patient himself or by his legal representative, such as a court-appointed supervisor or by an authorized proxy authorized representative or by a consultant

Exclusion criteria

  1. Patients with a life expectancy of less than 90 days due to medical conditions that are not associated with postoperative peritonitis or with sepsis / septic shock
  2. Pregnant, breastfeeding women
  3. Minors (< 18 years)
  4. Patients with a known dialysis-requiring chronic renal function (creatinine ≥ 3.4 mg / dl or creatinine clearance ≤ 30 mL / min / 1.73 m2)
  5. Patients with acute, primary non-infectious pancreatitis or mediastinitis
  6. BMI> 40
  7. Patients with a contraindication to study medication
  8. Participate in another medication study within the last 30 days
  9. Persons who are in a relationship of dependency or employment relationship with the sponsor or auditor
  10. Persons who are placed in an institution on a judicial or administrative order

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03334006


Locations
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Austria
LKH-Univ. Klinikum Graz
Graz, Austria, 8020
Medizinische Universität Wien
Wien, Austria, 1090
Germany
University Hospital Aachen
Aachen, Germany, 52074
Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH
Bochum, Germany, 44892
Klinikum Westfalen, Knappschaftskrankenhaus Dortmund
Dortmund, Germany, 44309
Universitätsklinikum Carl Gustav Carus
Dresden, Germany, 01307
Universitätsklinikum Frankfurt
Frankfurt, Germany, 60590
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Universitätsklinikum Heidelberg
Heidelberg, Germany, 69120
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Germany, 55131
Klinikum der Universität München
München, Germany, 81377
Sponsors and Collaborators
RWTH Aachen University
Biotest
Investigators
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Principal Investigator: Gernot Marx, Univ.-Prof. RWTH Aachen University
Publications:
Kujath P., Rodloff Peritonitis UNI-MED, 2001 ISBN 3-8999-549-5

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT03334006    
Other Study ID Numbers: 15-167
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: January 23, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RWTH Aachen University:
Pentaglobin®
Personalised Medicine
Additional relevant MeSH terms:
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Peritonitis
Infection
Intraabdominal Infections
Peritoneal Diseases
Digestive System Diseases