MedDRA version: 19.0 Level: PT Classification code 10040047 Term: Sepsis System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Anticholium
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use
Sponsors
Ruprecht-Karls-University Heidelberg, Med Faculty represented by Universitätsklinikum Heidelberg and its Commercial D
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Up for inclusion are all patients who fulfil all of the following criteria 1. Age at least 18 and not more than 85 years 2. APACHE II-Score =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Up for exclusion are all patients who fulfil at least one of the following criteria: 1. known oversensitivity towards physostigminsalicylate, sodiummetabisulphite, sodiumethylenediaminetetraacetic acid or one of the remaining ingridients of Anticholium® 2. known contraindications* against Anticholium® - gangrene - coronary heart disease 3. known absolute contraindications* against Anticholium® - myotonic dytrophy - depolarization block after depolarising muscle relaxants - intoxications through “irreversible acting” cholinesterase inhibitors - closed traumatic brain injuries - obstructions in the gastrointestinal tract (mechanic constipation) - obstructions in the urinary tract (mechanic urinary retention) 4. known relative contraindications* against Anticholium® - bronchial asthma - bradycardia - AV-conduction disorders 5. status post splenectomy 6.status post organ transplantation 7. positive pregnancy test, pregnancy and breastfeeding 8. participation in another clinical trial according to AMG or the follow-up period of another trial according to the AMG
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The present randomised, placebo-controlled, double-blind, monocentre study on the application of physostigminsalicylate (Anticholium®) as adjunctive measure in perioperative sepsis/septic shock is expected to bring forward a proof of efficacy in man and to show that the cholinergic anti-inflammatory pathway may be transferred into clinical use. ;Secondary Objective: The tests conducted in the scientific framework programme will shed more light on the complex interaction of interleukin-2, of interleukin-2-receptor, of TNF-alpha, of RAGE, of HMGB1, of AGEs, of NF-kappa-B in human sepsis and at the same time clarify whether RAGe may be considered for diagnostic marker. ;Primary end point(s): Primary outcome measure / efficacy endpoint is the mean SOFA-Score (Sequential Organ Failure Assessment Score) of seriously ill patients with perioperative sepsis/septic shock due to an intraabdominal infection during the treatment and in the subsequent time under intensive care. ;Timepoint(s) of evaluation of this end point: Visits 0, 2 to 7, 8 to 16, 17, 18, 19, 20 and end of study visit (within 24 hours before treatment start, 2 hours ± 30 minutes, 24 hours ± 2 hours, 48 hours ± 2 hours, 72 hours ± 2 hours, 96 hours ± 2 hours after treatment start, 6 days ± 4 hours, 7 days ± 4 hours, 8 days ± 8 hours, 9 days ± 8 hours, 10 days ± 8 hours, 11 days ± 8 hours, 12 days ± 8 hours, 13 days ± 8 hours, 14 days ± 8 hours after treatment start, 28 days ± 8 hours after treatment start, 30 days ± 8 hours after treatment start, 84 days ± 8 hours after treatment start, 90 days ± 8 hours after treatment start and day of discharge/transferral from intensive care unit; end of study visit is not done in case of death) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcome measure(s) / efficacy endpoint(s) are direct patienztrelevant - the duration of artificial ventilation - the duration of stay under intensive care and in hospital - the 30- and 90-day mortality on surrogate and scores ( indirect patientrelevant) - arterial blood gas( analys)es - central venous blood gas( analys)es - PaO2/FiO2 - platelet count - leukocyte count - creatinine - urea - total bilirubin - C-reactive protein - Quick's test (prothrombin time) - D-dimer - procalcitonin - interleukin-6 - thrombin-antithrombin-complex - mean arterial pressure and use of vasopressors (frequency and duration) - the use of renal replacement therapy (frequency and duration) - GCS-score - APACHE II-score - SAPS II and on the occurrence of side effects as - nausea, vomiting - changes in heart rate: clinically relevant decrease in heart rate or clinically relevant increase in heart rate - changes in arterial pressure: clinically relevant decrease in arterial pressure - changes in airway resistance spontaneous breathing: acute shortness of breath artificial ventilation: clinically relevant decrease in ventilation volume at steady ventilation pressure or clinically relevant increase in ventilation pressure at steady ventilation volume (?pressure = peak pressure - end-expiratory pressure) ;Timepoint(s) of evaluation of this end point: Visits 0, 2 to 7, 8 to 16, 17, 18, 19, 20 and end of study visit (within 24 hours before treatment start, 2 hours ± 30 minutes, 24 hours ± 2 hours, 48 hours ± 2 hours, 72 hours ± 2 hours, 96 hours ± 2 hours after treatment start, 6 days ± 4 hours, 7 days ± 4 hours, 8 days ± 8 hours, 9 days ± 8 hours, 10 days ± 8 hours, 11 days ± 8 hours, 12 days ± 8 hours, 13 days ± 8 hours, 14 days ± 8 hours after treatment start, 28 days ± 8 hours after treatment start, 30 days ± 8 hours after treatment start, 84 days ± 8 hours afte | — |
Countries
Germany
Contacts
Public ContactDepartment of Anesthesiology
University Hospital Heidelberg
Outcome results
None listed