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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03334006
Other study ID # 15-167
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date November 20, 2017
Est. completion date March 2028

Study information

Verified date April 2024
Source RWTH Aachen University
Contact Katharina Alack, Dr. rer. nat.
Email PEPPER@ukaachen.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date March 2028
Est. primary completion date September 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
Pentaglobin®/Standard of Care
Standard of Care treatment + Pentaglobin®

Locations

Country Name City State
Austria Medizinische Universität Wien, Klinische Abteilung für Allgemeine Anästhesie und Intensivmedizin Wien
Germany Uniklinik RWTH Aachen, Klinik für Operative Intensivmedizin und Intermediate Care Aachen
Germany Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Klinik für Anästesiologie, Intensivmedizin und Schmerztherapie Bochum
Germany Klinikum Westfalen, Knappschaftskrankenhaus Dortmund, Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie Dortmund
Germany Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie Dresden
Germany Universitätsklinikum Düsseldorf, Klinik für Anästhesiologie Düsseldorf
Germany Universitätsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin Essen Nordrhein-Westfalen
Germany Universitätklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie Frankfurt
Germany Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie Freiburg
Germany Universitätsklinikum Hamburg-Eppendorf, Zentrum für Anästhesiologie und Intensivmedizin Hamburg
Germany Medizinische Hochschule Hannover, Zentrum für Anästhesiologie und Intensivmedizin Hannover
Germany Universitätsklinikum Heidelberg, Anästhesiologische Klinik Heidelberg
Germany Klinikum Magdeburg, Klinik für Intensivmedizin Magdeburg
Germany Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Mainz
Germany Klinikum der Universität München, Klinikum der Universität München, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie München
Germany Heinrich-Braun-Klinikum gGmbH, Klinik für Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie Zwickau

Sponsors (2)

Lead Sponsor Collaborator
RWTH Aachen University Biotest

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (37)

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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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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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. — View Citation

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

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. — View Citation

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. — View Citation

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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. — View Citation

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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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* Note: There are 37 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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 was obtained are assigned a score of 10 points. 7 days
Secondary Death within 28 days Evaluation of death within 28-days. 28 days
Secondary Death within 90 days Evaluation of death within 90-days. 90 days
Secondary Change in MOF Score from baseline to day 5 Change in MOF Score from baseline to day 5. 5 days
Secondary Multi-Organ Failure (i.e., > 4 MOF points) on Day 7 MOF (i.e., > 4 MOF points) on Day 7 Day 7 7 days
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