Clinical trial NCT04130230: Adjuvant Use of Neostigmine in Sepsis and Septic Shock.
Official title: Safety and Efficacy of Neostigmine Infusion as Adjuvant Therapy in Sepsis and Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sepsis, Septic Shock
Lead sponsor: Mansoura University
Sponsor class: OTHER
First posted: 2019-10-17
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Sequential organ failure assessment (SOFA score)
timeFrame: Change from baseline SOFA score at five days
Secondary outcomes:
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta University Hospital
state: EL-Gharbia
Study officials:
affiliation: Faculty of Pharmacy-Mansoura University
name: Mamdouh M El-Shishtawy, Professor
role: STUDY_CHAIR
References:
citation: El-Tamalawy MM, Soliman MM, Omara AF, Rashad A, Ibrahim OM, El-Shishtawy MM. Efficacy and Safety of Neostigmine Adjunctive Therapy in Patients With Sepsis or Septic Shock: A Randomized Controlled Trial. Front Pharmacol. 2022 Mar 7;13:855764. doi: 10.3389/fphar.2022.855764. eCollection 2022.