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

Обзор

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.

Подробное описание

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 0.4 ml/kg body weight/hour until the total dose of 7 ml/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 (\< 700 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.

Вмешательства

• Препарат Pentaglobin®/Standard of Care
  Standard-of-Care treatment + Pentaglobin®

Первичные конечные точки

• 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. [Срок оценки: 7 days]

Вторичные конечные точки (4)

• Death within 28 days [Срок оценки: 28 days]
• Death within 90 days [Срок оценки: 90 days]
• Change in MOF Score from baseline to day 5 [Срок оценки: 5 days]
• Multi-Organ Failure (i.e., > 4 MOF points) on day 7 [Срок оценки: 7 days]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 19 центров

• Universitätsklinikum Tübingen, Universitätsklinik für Anästhesiologie und Intensivmedizin — Tübingen
• Universitätsklinikum Regensburg, Klinik für Anästhesiologie — Regensburg
• Universitätsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin — Essen
• Charité - Universitätsmedizin Berlin, Klinik für Anästhesiologie mit Schwerpunkt operative — Berlin
• Uniklinik RWTH Aachen, Klinik für Operative Intensivmedizin und Intermediate Care — Aachen
• Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Klinik für Anästhesiologie, Inte — Bochum
• Klinikum Westfalen, Knappschaftskrankenhaus Dortmund, Klinik für Anästhesiologie, operativ — Dortmund
• Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Anästhesiologie und Inte — Dresden
• … и ещё 11 центров

Австрия · 1 центр

• Medizinische Universität Wien, Klinische Abteilung für Allgemeine Anästhesie und Intensivm — Vienna

Публикации

• Kujath P., Rodloff Peritonitis UNI-MED, 2001 ISBN 3-8999-549-5
• 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
• 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
• 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
• 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
• Maruna P, Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin. Physiol Res. 2000;49 Suppl 1:S57-61. PMID 10984072
• 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
• 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

Идентификаторы

NCT: NCT03334006 · 15-167 · 2024-513526-27-00 · 2016-001788-34

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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