Anticholium® Per Se

Sepsis Clinical Trial

Official title:

Anticholium® Per Se a Randomized, Double-blind, Placebo-controlled, Monocentric Trial on the Adjunctive Use of Physostigmine Salicylate (Anticholium®) in Perioperative Sepsis and Septic Shock

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03013322
• Other study ID #: D.10060224
• Status: Completed
• Phase: N/A
• First received: January 1, 2017
• Last updated: January 25, 2018
• Start date: January 28, 2015
• Est. completion date: February 18, 2017

Study information

• Verified date: January 2018
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Anticholium® per Se is a randomized, double-blind, placebo-controlled, monocentric trial to assess whether the CAP can be transferred from bench to bedside. In this pilot study, 20 patients with perioperative sepsis and septic shock as a result of intra-abdominal infection are enrolled. According to randomization, participants are treated with physostigmine salicylate (verum group) or 0.9% sodium chloride (placebo group) for up to 5 days. The mean Sequential Organ Failure Assessment (SOFA) score during treatment and subsequent intensive care of up to 14 days is used as surrogate outcome (primary endpoint). Secondary outcome measures include 30- and 90-day mortality. An embedded pharmacokinetics and pharmacodynamics study investigates plasma concentrations of physostigmine and its metabolite eseroline. Further analyses will contribute to the understanding of the role of various cytokines in the pathophysiology of human sepsis. A computer-generated list is used for blocked randomization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 18, 2017
• Est. primary completion date: February 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion criteria

• Age 18-85 years

• APACHE II score <34

• Intra-abdominal infection

• findings of diffuse peritonitis or a circumscribed abscess

• Perioperative sepsis

• and secure evidence of infection, clinically backed up or secured microbiologically

• =2 of the following four criteria:

• fever =38.0° C or hypothermia =36.0° C secured by rectal intravesical or intravascular measurement

• tachycardia =90/min

• tachypnea =20/min or hyperventilation secured by arterial blood gas analysis with PaCO2 =4.3 kPa or 33 mmHg or mechanical artificial respiration

• leukocytosis =12,000/mm³ or leukopenia =4000/mm³ or =10% immature neutrophils in the differential count

• Shock (<24 h duration): necessary use of vasopressors despite adequate fluid resuscitation to keep systolic blood pressure =90 mmHg or mean blood pressure =70 mmHg

• No more than one planned and/or one emergency basis/as an emergency procedure performed since admission (no repeated revisions)

• No infaust prognosis of a primary or concomitant illness, expecting the death within the follow-up phase

• No do-not-resuscitate order

• Written informed consent of full-age patients/their legal guardian to participate [written consent (according to AMG § 40 (1) 3b)] and unable to consent adults [§ 41 (1) 2 AMG)]

Exclusion criteria

• Known hypersensitivity to physostigmine salicylate, sodium metabisulfite, sodium EDTA, or any of the other ingredients of Anticholium®

• Known contraindications against Anticholium®: gangrene, coronary artery disease

• Known absolute contraindications against Anticholium®: myotonic dystrophy; depolarization block by depolarizing muscle relaxants; intoxication by "irreversibly acting" cholinesterase inhibitors; closed craniocerebral trauma; obstruction in the gastrointestinal tract (mechanical constipation); obstruction in the urinary tract (mechanical urinary retention)

• Known relative contraindications against Anticholium®: bronchial asthma; bradycardia; AV-conduction disturbances

• Having undergone splenectomy

• Having undergone solid organ transplantation

• Positive pregnancy test, pregnancy, and lactation

• Participation in another clinical trial, according to AMG or the follow-up phase of another study, according to AMG

Related Conditions & MeSH terms

• Perioperative Period
• Sepsis
• Shock, Septic

Intervention

Drug:
• Physostigmine

• Isotonic Saline

Locations

Country	Name	City	State
Germany	University Hospital Heidelberg	Heidelberg	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Heidelberg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	microbiological analyses of potential pathogens including susceptibility tests		up to 90 days
Other	plasma concentrations of physostigmine	determined with a validated high-performance liquid chromatography (HPLC) method	up to 6 d, assessed 3±2 min after study med, end of initial ±2 min, 10, 20, 30±2 min, 1 h±10 min, 2 h±30 min, 24, 48, 72, 96, 120±2 h after continuous (end of study med), 10, 20, 30±2 min, 1, 2 h±10 min after end of study med, 6 d ± 4 h after continuous
Other	plasma concentrations of eseroline	determined with a validated high-performance liquid chromatography (HPLC) method	up to 6 d, assessed 3±2 min after study med, end of initial ±2 min, 10, 20, 30±2 min, 1 h±10 min, 2 h±30 min, 24, 48, 72, 96, 120±2 h after continuous (end of study med), 10, 20, 30±2 min, 1, 2 h±10 min after end of study med, 6 d ± 4 h after continuous
Other	acetylcholinesterase activity	determined with ChE check mobile (Securetec, Neubiberg, Germany) from remaining material drawn for routine blood gas analyses (arterial samples)	up to 6 d, assessed 1 h±10 min, 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h after continuous infusion is commenced
Other	butyrylcholinesterase activity	determined with ChE check mobile (Securetec, Neubiberg, Germany) from remaining material drawn for routine blood gas analyses (arterial samples)	up to 6 d, assessed 1 h±10 min, 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h after continuous infusion is commenced
Primary	mean Sequential Organ Failure Assessment (SOFA) score	The mean SOFA score (at least two individual values) during treatment and subsequent intensive care of up to 14 days is used as surrogate outcome in critically ill patients with perioperative sepsis and septic shock due to intra-abdominal infection.	up to 14 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h after continuous infusion is commenced
Secondary	duration of artificial ventilation		up to 90 d
Secondary	duration of intensive care		up to 90 d
Secondary	length of stay		up to 90 d
Secondary	30-day mortality		30 d
Secondary	90-day mortality		90 d
Secondary	arterial blood gas analyses		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	central venous blood gas analyses		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	partial pressure of arterial oxygen (PaO2)		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	fraction of inspired oxygen (FiO2)		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	platelet count		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	leukocyte count		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	creatinine		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	urea		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	total bilirubin		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	C-reactive protein		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	prothrombin time		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	D-dimer		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	procalcitonin		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	IL-6		up to 30 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 14 d±8 h, 28 d±8 h, 30 d±8 h after continuous infusion is commenced
Secondary	thrombin-antithrombin complex		up to 30 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 14 d±8 h, 28 d±8 h, 30 d±8 h after continuous infusion is commenced
Secondary	mean blood pressure		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	frequency of vasopressors		up to 90 days
Secondary	duration of vasopressors		up to 90 days
Secondary	frequency of renal replacement therapy		up to 90 days
Secondary	duration of renal replacement therapy		up to 90 days
Secondary	Glasgow Coma Scale (GCS) score		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	Acute Physiology And Chronic Health Evaluation (APACHE) II score		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	Simplified Acute Physiology Score (SAPS) II score		up to 90 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h, 7 d±4 h, 8 d±8 h, 9 d±8 h, 10 d±8 h, 11 d±8 h, 12 d±8 h, 13 d±8 h, 14 d±8 h, 28 d±8 h, 30 d±8 h, 84 d±8 h, 90 d±8 h after continuous infusion is commenced
Secondary	occurrence of side effects	nausea or vomiting, clinically relevant changes in heart rate or blood pressure (mainly hypotension), and clinically relevant changes in airway resistance (mainly bronchiospasms as a result of hypersensitivity reactions to the sodium metabisulfite contained in the investigational medicinal product spontaneous breathing: acute dyspnea or artificial ventilation: clinically relevant decline in respiratory volume at constant pressure settings, or clinically relevant incline in peak or inspiratory pressures at constant respiratory volumes)	up to 6 d, assessed 2 h±30 min, 24±2 h, 48±2 h, 72±2 h, 96±2 h, 120±2 h, 6 d±4 h after continuous infusion is commenced