Adjuvant Use of Neostigmine in Sepsis and Septic Shock.

NCT04130230 | Completed Phase 2

• 1 other identifier: 2019-3
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis, Septic Shock

Outcome Measures

Primary Outcomes (1)

• Sequential organ failure assessment (SOFA score)

  Increase in SOFA score is associated with worse outcome.

  Change from baseline SOFA score at five days

Study Arms (2)

Neostigmine group

EXPERIMENTAL

This arm will receive -in addition to standard therapy for sepsis and septic shock-Neostigmine methylsulfate ampoule diluted in normal saline, and administered as continuous infusion for five days. The rate of infusion is 0.2 mg/hr.

Drug: Neostigmine

Standard group

PLACEBO COMPARATOR

This arm will receive the standard therapy for sepsis and septic shock only and followed for five days.

Drug: Standard therapy

Interventions

Neostigmine DRUG

Neostigmine continuous infusion plus standard therapy for sepsis and septic shock.

Also known as: Choline esterase inhibitor

Neostigmine group

Standard therapy DRUG

Standard therapy for sepsis and septic shock

Standard group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Fever ≥ 38 °C or hypothermia ≤ 36 °C.
• Tachycardia ≥ 100/min.
• Tachypnea ≥ 20/min or hyperventilation.
• Leukocytosis ≥ 12000/mm3 or leukopenia ≤ 4000/mm3 or ≥ 10% immature neutrophils in the differential count.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mansoura University: lead

Study Sites (1)

Tanta University Hospital

Tanta, EL-Gharbia, 31527, Egypt

Location

Related Publications (1)

• 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.

  PMID: 35330830 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Neostigmine; Standard of Care

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Mamdouh M El-Shishtawy, Professor

  Faculty of Pharmacy-Mansoura University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer

Study Record Dates

• First Submitted: October 8, 2019
• First Posted: October 17, 2019
• Study Start: March 6, 2019
• Primary Completion: August 10, 2021
• Study Completion: October 1, 2021
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)