Adjuvant Use of Neostigmine in Sepsis and Septic Shock.

Sepsis, Septic Shock Clinical Trial

Official title:

Safety and Efficacy of Neostigmine Infusion as Adjuvant Therapy in Sepsis and Septic Shock

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04130230
• Other study ID #: 2019-3
• Status: Recruiting
• Phase: Phase 2
• Start date: March 6, 2019
• Est. completion date: June 2020

Study information

• Verified date: October 2019
• Source: Mansoura University
• Contact: Mona M El-Tamalawy, Master
• Phone: 01220650700
• Email: mona.m.eltamalawy[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The inflammatory response represents an important, central component of sepsis. Therefore, it is believed that blunting inflammation will decrease mortality. In vivo test series with mice that had undergone cecal ligation and puncture (recognized sepsis model), physostigmine salicylate significantly inhibited the release of various cytokines (tumor necrosis factor α, interleukin1β, and interleukin 6). These results were similar to those obtained by vagus nerve stimulation.

In animal sepsis model using physostigmine not only decreased inflammation but also, diminished the decrease in blood pressure following infection.

Animals treated with the peripheral choline esterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals. Therefore, this study aims to investigate the efficacy of choline esterase inhibitors as adjuvant therapy in patients with sepsis or septic shock. Outcome measures include: percentage reduction in procalcitonin blood level, percentage of patients achieving significant reduction in procalcitonin levels, Mean Sequential Organ Failure Assessment score, percentage decrease in lactate dehydrogenase blood level, length of stay in hospital intensive care unit, and in hospital mortality.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2020
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Age 18-85 years.

• Patients diagnosed with sepsis or septic shock according to Third International Consensus Definitions for Sepsis and Septic Shock mentioned above.

• Patients who have = 2 of the following four criteria plus documented infection:

1. Fever = 38 °C or hypothermia = 36 °C.

2. Tachycardia = 100/min.

3. Tachypnea = 20/min or hyperventilation.

4. Leukocytosis = 12000/mm3 or leukopenia = 4000/mm3 or = 10% immature neutrophils in the differential count.

Exclusion criteria:

• Known hypersensitivity to choline esterase inhibitors.

• Known absolute contra-indications against choline esterase inhibitors such as, 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 choline esterase inhibitors: bronchial asthma; bradycardia; AV-conduction disturbances.

• Having undergone solid organ transplantation.

• Pregnant and lactating women.

• Participation in another clinical trial.

• Presence of primary or concomitant illness, impending death.

Related Conditions & MeSH terms

• Sepsis
• Sepsis, Septic Shock
• Shock
• Shock, Septic
• Toxemia

Intervention

Drug:
• Neostigmine
Neostigmine continuous infusion plus standard therapy for sepsis and septic shock.
• Standard therapy
Standard therapy for sepsis and septic shock

Locations

Country	Name	City	State
Egypt	Tanta University Hospital	Tanta	EL-Gharbia

Sponsors (1)

Lead Sponsor	Collaborator
Mansoura University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sequential organ failure assessment (SOFA score)	Increase in SOFA score is associated with worse outcome.	Change from baseline SOFA score at five days