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

NCT03334006 | Recruiting Phase 2 DMC

• 3 other identifiers: 15-1672024-513526-27-002016-001788-34
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 20

Brief Summary

The aim of this prospective, randomized, controlled trial is to provide evidence for adjuvant IgGAM treatment with regard to

1. 1.Improvement of patient outcomes for peritonitis. Improvement in outcome will be determined by scores such as MOF, SOFA and survival.
2. 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. 3.In addition, these biomarkers could help to guide a targeted, i.e. "personalized", adjuvant therapy with Pentaglobin® (IgGAM) in the indication of peritonitis.

Conditions

Peritonitis; Sepsis; Septic Shock

Keywords

Pentaglobin®; Personalized Medicine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Death within 28 days

  28 days

• 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

Study Arms (2)

Control arm

NO INTERVENTION

Standard of Care treatment

Verum arm

ACTIVE COMPARATOR

Standard of Care treatment + Pentaglobin®

Drug: Pentaglobin®/Standard of Care

Interventions

Pentaglobin®/Standard of Care DRUG

Standard-of-Care treatment + Pentaglobin®

Verum arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• The patient is a minor (\< 18 years of age).
• The patient has known chronic renal dysfunction requiring dialysis (creatinine ≥ 3.4 mg / dl or creatinine clearance ≤ 30 mL/min/1.73 m²).
• The patient has acute, primarily non-infectious pancreatitis or mediastinitis.
• The patient has a BMI \> 40.
• The patient has any contraindication to study drug.
• The patient has participated in another clinical trial within the last 30 days.
• The patient is in a dependent or employment relationship with the sponsor or investigator.
• The patient is institutionalized by court or government order.

Sponsors & Collaborators

• RWTH Aachen University: lead
• Biotest: collaborator

Study Sites (20)

Medizinische Universität Wien, Klinische Abteilung für Allgemeine Anästhesie und Intensivmedizin

Vienna, 1090, Austria

RECRUITING

Universitätsklinikum Tübingen, Universitätsklinik für Anästhesiologie und Intensivmedizin

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Universitätsklinikum Regensburg, Klinik für Anästhesiologie

Regensburg, Bavaria, 93053, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin

Essen, North Rhine-Westphalia, 45147, Germany

RECRUITING

Charité - Universitätsmedizin Berlin, Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin

Berlin, State of Berlin, 12203, Germany

RECRUITING

Uniklinik RWTH Aachen, Klinik für Operative Intensivmedizin und Intermediate Care

Aachen, 52074, Germany

RECRUITING

Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie

Bochum, 44892, Germany

RECRUITING

Klinikum Westfalen, Knappschaftskrankenhaus Dortmund, Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie

Dortmund, 44309, Germany

TERMINATED

Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie

Dresden, 01307, Germany

WITHDRAWN

Universitätsklinikum Düsseldorf, Klinik für Anästhesiologie

Düsseldorf, 40225, Germany

WITHDRAWN

Universitätklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie

Frankfurt, 60590, Germany

RECRUITING

Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie

Freiburg im Breisgau, 79106, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin

Hamburg, 20246, Germany

RECRUITING

Medizinische Hochschule Hannover, Zentrum für Anästhesiologie und Intensivmedizin

Hanover, 30625, Germany

WITHDRAWN

Universitätsklinikum Heidelberg, Anästhesiologische Klinik

Heidelberg, 69120, Germany

WITHDRAWN

Klinikum Magdeburg, Klinik für Intensivmedizin

Magdeburg, 39130, Germany

WITHDRAWN

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie

Mainz, 55131, Germany

WITHDRAWN

Klinikum der Universität München, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie

München, 81377, Germany

RECRUITING

Klinikum Nürnberg, Klinik für Anästhesiologie und operative Intensivmedizin

Nuremberg, 90419, Germany

RECRUITING

Heinrich-Braun-Klinikum gGmbH, Klinik für Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie

Zwickau, 08060, Germany

RECRUITING

Related Publications (38)

• Kujath P., Rodloff Peritonitis UNI-MED, 2001 ISBN 3-8999-549-5

  BACKGROUND

• Chang HJ, Lynm C, Glass RM. JAMA patient page. Sepsis. JAMA. 2010 Oct 27;304(16):1856. doi: 10.1001/jama.304.16.1856. No abstract available.

  PMID: 20978264 BACKGROUND

• Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, Vadas L, Pugin J; Geneva Sepsis Network. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001 Aug 1;164(3):396-402. doi: 10.1164/ajrccm.164.3.2009052.

  PMID: 11500339 BACKGROUND

• Heyland DK, Muscedere J, Drover J, Jiang X, Day AG; Canadian Critical Care Trials Group. Persistent organ dysfunction plus death: a novel, composite outcome measure for critical care trials. Crit Care. 2011;15(2):R98. doi: 10.1186/cc10110. Epub 2011 Mar 18.

  PMID: 21418560 BACKGROUND

• Muller B, Becker KL, Schachinger H, Rickenbacher PR, Huber PR, Zimmerli W, Ritz R. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med. 2000 Apr;28(4):977-83. doi: 10.1097/00003246-200004000-00011.

  PMID: 10809269 BACKGROUND

• Maruna P, Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin. Physiol Res. 2000;49 Suppl 1:S57-61.

  PMID: 10984072 BACKGROUND

• Clec'h C, Fosse JP, Karoubi P, Vincent F, Chouahi I, Hamza L, Cupa M, Cohen Y. Differential diagnostic value of procalcitonin in surgical and medical patients with septic shock. Crit Care Med. 2006 Jan;34(1):102-7. doi: 10.1097/01.ccm.0000195012.54682.f3.

  PMID: 16374163 BACKGROUND

• Monneret G, Doche C, Durand DV, Lepape A, Bienvenu J. Procalcitonin as a specific marker of bacterial infection in adults. Clin Chem Lab Med. 1998 Jan;36(1):67-8. doi: 10.1515/CCLM.1998.012. No abstract available.

  PMID: 9594089 BACKGROUND

• Brunkhorst FM. [Sepsismarker--what is useful?]. Dtsch Med Wochenschr. 2008 Nov;133(48):2512-5. doi: 10.1055/s-0028-1100949. Epub 2008 Nov 19. No abstract available. German.

  PMID: 19021084 BACKGROUND

• Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006 Jul 1;174(1):84-93. doi: 10.1164/rccm.200512-1922OC. Epub 2006 Apr 7.

  PMID: 16603606 BACKGROUND

• Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253-78. doi: 10.1146/annurev.iy.08.040190.001345. No abstract available.

  PMID: 2188664 BACKGROUND

• Panacek EA, Marshall JC, Albertson TE, Johnson DH, Johnson S, MacArthur RD, Miller M, Barchuk WT, Fischkoff S, Kaul M, Teoh L, Van Meter L, Daum L, Lemeshow S, Hicklin G, Doig C; Monoclonal Anti-TNF: a Randomized Controlled Sepsis Study Investigators. Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med. 2004 Nov;32(11):2173-82. doi: 10.1097/01.ccm.0000145229.59014.6c.

  PMID: 15640628 BACKGROUND

• Kuster H, Weiss M, Willeitner AE, Detlefsen S, Jeremias I, Zbojan J, Geiger R, Lipowsky G, Simbruner G. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet. 1998 Oct 17;352(9136):1271-7. doi: 10.1016/S0140-6736(98)08148-3.

  PMID: 9788457 BACKGROUND

• Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, Weber-Carstens S, Hasper D, Keh D, Zuckermann H, Reinke P, Volk HD. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med. 2009 Oct 1;180(7):640-8. doi: 10.1164/rccm.200903-0363OC. Epub 2009 Jul 9.

  PMID: 19590022 BACKGROUND

• Schefold JC, von Haehling S, Corsepius M, Pohle C, Kruschke P, Zuckermann H, Volk HD, Reinke P. A novel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin 6, and complement-activating product 5a. Shock. 2007 Oct;28(4):418-25. doi: 10.1097/shk.0b013e31804f5921.

  PMID: 17558345 BACKGROUND

• Bermejo-Martin JF, Rodriguez-Fernandez A, Herran-Monge R, Andaluz-Ojeda D, Muriel-Bombin A, Merino P, Garcia-Garcia MM, Citores R, Gandia F, Almansa R, Blanco J; GRECIA Group (Grupo de Estudios y Analisis en Cuidados Intensivos). Immunoglobulins IgG1, IgM and IgA: a synergistic team influencing survival in sepsis. J Intern Med. 2014 Oct;276(4):404-12. doi: 10.1111/joim.12265. Epub 2014 May 29.

  PMID: 24815605 BACKGROUND

• Giamarellos-Bourboulis EJ, Apostolidou E, Lada M, Perdios I, Gatselis NK, Tsangaris I, Georgitsi M, Bristianou M, Kanni T, Sereti K, Kyprianou MA, Kotanidou A, Armaganidis A; Hellenic Sepsis Study Group. Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome. Crit Care. 2013 Oct 21;17(5):R247. doi: 10.1186/cc13073.

  PMID: 24144038 BACKGROUND

• Tamayo E, Fernandez A, Almansa R, Carrasco E, Goncalves L, Heredia M, Andaluz-Ojeda D, March G, Rico L, Gomez-Herreras JI, de Lejarazu RO, Bermejo-Martin JF. Beneficial role of endogenous immunoglobulin subclasses and isotypes in septic shock. J Crit Care. 2012 Dec;27(6):616-22. doi: 10.1016/j.jcrc.2012.08.004. Epub 2012 Oct 22.

  PMID: 23089676 BACKGROUND

• Koo DJ, Zhou M, Chaudry IH, Wang P. The role of adrenomedullin in producing differential hemodynamic responses during sepsis. J Surg Res. 2001 Feb;95(2):207-18. doi: 10.1006/jsre.2000.6013.

  PMID: 11162047 BACKGROUND

• Wang P, Ba ZF, Cioffi WG, Bland KI, Chaudry IH. The pivotal role of adrenomedullin in producing hyperdynamic circulation during the early stage of sepsis. Arch Surg. 1998 Dec;133(12):1298-304. doi: 10.1001/archsurg.133.12.1298.

  PMID: 9865646 BACKGROUND

• Marino R, Struck J, Maisel AS, Magrini L, Bergmann A, Di Somma S. Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis. Crit Care. 2014 Feb 17;18(1):R34. doi: 10.1186/cc13731.

  PMID: 24533868 BACKGROUND

• Ueda S, Nishio K, Minamino N, Kubo A, Akai Y, Kangawa K, Matsuo H, Fujimura Y, Yoshioka A, Masui K, Doi N, Murao Y, Miyamoto S. Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome. Am J Respir Crit Care Med. 1999 Jul;160(1):132-6. doi: 10.1164/ajrccm.160.1.9810006.

  PMID: 10390390 BACKGROUND

• Adamzik M, Frey UH, Mohlenkamp S, Scherag A, Waydhas C, Marggraf G, Dammann M, Steinmann J, Siffert W, Peters J. Aquaporin 5 gene promoter--1364A/C polymorphism associated with 30-day survival in severe sepsis. Anesthesiology. 2011 Apr;114(4):912-7. doi: 10.1097/ALN.0b013e31820ca911.

  PMID: 21427539 BACKGROUND

• Zhu Y, Qiu HB, Liu JT, Wang Y, Lin HY, Xu Y, Jiang L, Shi Y, Zhu X, Ning B, Cheng R, Xie ZY, Ma PL. [Effect of endothelial nitric oxide synthase gene polymorphisms upon disease severity and outcome in septic patients]. Zhonghua Yi Xue Za Zhi. 2010 Apr 6;90(13):906-11. Chinese.

  PMID: 20646511 BACKGROUND

• Thair SA, Walley KR, Nakada TA, McConechy MK, Boyd JH, Wellman H, Russell JA. A single nucleotide polymorphism in NF-kappaB inducing kinase is associated with mortality in septic shock. J Immunol. 2011 Feb 15;186(4):2321-8. doi: 10.4049/jimmunol.1002864. Epub 2011 Jan 21.

  PMID: 21257964 BACKGROUND

• Beyer K, Menges P, Kessler W, Heidecke CD. [Pathophysiology of peritonitis]. Chirurg. 2016 Jan;87(1):5-12. doi: 10.1007/s00104-015-0117-6. German.

  PMID: 26661744 BACKGROUND

• Rodriguez A, Rello J, Neira J, Maskin B, Ceraso D, Vasta L, Palizas F. Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery. Shock. 2005 Apr;23(4):298-304. doi: 10.1097/01.shk.0000157302.69125.f8.

  PMID: 15803051 BACKGROUND

• Cavazzuti I, Serafini G, Busani S, Rinaldi L, Biagioni E, Buoncristiano M, Girardis M. Early therapy with IgM-enriched polyclonal immunoglobulin in patients with septic shock. Intensive Care Med. 2014 Dec;40(12):1888-96. doi: 10.1007/s00134-014-3474-6. Epub 2014 Sep 13.

  PMID: 25217146 BACKGROUND

• Alejandria MM, Lansang MA, Dans LF, Mantaring JB 3rd. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013 Sep 16;2013(9):CD001090. doi: 10.1002/14651858.CD001090.pub2.

  PMID: 24043371 BACKGROUND

• Janssens U. [Treatment of sepsis and septic shock with immunoglobulins]. Dtsch Med Wochenschr. 2014 Jan;139(5):178. doi: 10.1055/s-0032-1329177. Epub 2014 Jan 21. No abstract available. German.

  PMID: 24449349 BACKGROUND

• Reinhart K, Brunkhorst FM, Bone HG, Bardutzky J, Dempfle CE, Forst H, Gastmeier P, Gerlach H, Grundling M, John S, Kern W, Kreymann G, Kruger W, Kujath P, Marggraf G, Martin J, Mayer K, Meier-Hellmann A, Oppert M, Putensen C, Quintel M, Ragaller M, Rossaint R, Seifert H, Spies C, Stuber F, Weiler N, Weimann A, Werdan K, Welte T; German Interdisciplinary Association for Intensive and Emergency Care Medicine; German Sepsis Society. [Prevention, diagnosis, treatment, and follow-up care of sepsis. First revision of the S2k Guidelines of the German Sepsis Society (DSG) and the German Interdisciplinary Association for Intensive and Emergency Care Medicine (DIVI)]. Anaesthesist. 2010 Apr;59(4):347-70. doi: 10.1007/s00101-010-1719-5. No abstract available. German.

  PMID: 20414762 BACKGROUND

• Goris RJ, te Boekhorst TP, Nuytinck JK, Gimbrere JS. Multiple-organ failure. Generalized autodestructive inflammation? Arch Surg. 1985 Oct;120(10):1109-15. doi: 10.1001/archsurg.1985.01390340007001.

  PMID: 4038052 BACKGROUND

• Lefering R, Goris RJ, van Nieuwenhoven EJ, Neugebauer E. Revision of the multiple organ failure score. Langenbecks Arch Surg. 2002 Apr;387(1):14-20. doi: 10.1007/s00423-001-0269-3. Epub 2002 Jan 31.

  PMID: 11981679 BACKGROUND

• Casserly B, Phillips GS, Schorr C, Dellinger RP, Townsend SR, Osborn TM, Reinhart K, Selvakumar N, Levy MM. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med. 2015 Mar;43(3):567-73. doi: 10.1097/CCM.0000000000000742.

  PMID: 25479113 BACKGROUND

• Weigelt JA. Empiric treatment options in the management of complicated intra-abdominal infections. Cleve Clin J Med. 2007 Aug;74 Suppl 4:S29-37. doi: 10.3949/ccjm.74.suppl_4.s29.

  PMID: 17847176 BACKGROUND

• Wong PF, Gilliam AD, Kumar S, Shenfine J, O'Dair GN, Leaper DJ. Antibiotic regimens for secondary peritonitis of gastrointestinal origin in adults. Cochrane Database Syst Rev. 2005 Apr 18;2005(2):CD004539. doi: 10.1002/14651858.CD004539.pub2.

  PMID: 15846719 BACKGROUND

• Mebazaa A, Laterre PF, Russell JA, Bergmann A, Gattinoni L, Gayat E, Harhay MO, Hartmann O, Hein F, Kjolbye AL, Legrand M, Lewis RJ, Marshall JC, Marx G, Radermacher P, Schroedter M, Scigalla P, Stough WG, Struck J, Van den Berghe G, Yilmaz MB, Angus DC. Designing phase 3 sepsis trials: application of learned experiences from critical care trials in acute heart failure. J Intensive Care. 2016 Mar 31;4:24. doi: 10.1186/s40560-016-0151-6. eCollection 2016.

  PMID: 27034779 BACKGROUND

• Kalvelage C, Zacharowski K, Bauhofer A, Gockel U, Adamzik M, Nierhaus A, Kujath P, Eckmann C, Pletz MW, Bracht H, Simon TP, Winkler M, Kindgen-Milles D, Albertsmeier M, Weigand M, Ellger B, Ragaller M, Ullrich R, Marx G. Personalized medicine with IgGAM compared with standard of care for treatment of peritonitis after infectious source control (the PEPPER trial): study protocol for a randomized controlled trial. Trials. 2019 Mar 4;20(1):156. doi: 10.1186/s13063-019-3244-4.

  PMID: 30832742 DERIVED

MeSH Terms

Conditions

Peritonitis; Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Intraabdominal Infections; Infections; Peritoneal Diseases; Digestive System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Gernot Marx, Univ.-Prof.

  RWTH Aachen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Center for Translational & Clinical Research (CTC-A)

CONTACT

PEPPER@ukaachen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 27, 2017
• First Posted: November 7, 2017
• Study Start: November 20, 2017
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (19); AU (1)