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Adjuvant Use of Neostigmine in Sepsis and Septic Shock.

Primary Purpose

Sepsis, Septic Shock

Status

Unknown status

Phase

Phase 2

Locations

Egypt

Study Type

Interventional

Intervention

Neostigmine

Standard therapy

About this trial

This is an interventional treatment trial for Sepsis, Septic Shock

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Tanta University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Neostigmine group

Standard group

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Sequential organ failure assessment (SOFA score)

Increase in SOFA score is associated with worse outcome.

Secondary Outcome Measures

Full Information

NCT ID

NCT04130230

First Posted

October 8, 2019

Last Updated

October 16, 2019

Sponsor

Mansoura University

1. Study Identification

Unique Protocol Identification Number

NCT04130230

Brief Title

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

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Unknown status

Study Start Date

March 6, 2019 (Actual)

Primary Completion Date

March 2020 (Anticipated)

Study Completion Date

June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mansoura University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sepsis, Septic Shock

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neostigmine group

Arm Type

Experimental

Arm Description

Arm Title

Standard group

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Neostigmine

Other Intervention Name(s)

Choline esterase inhibitor

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Standard therapy

Intervention Description

Standard therapy for sepsis and septic shock

Primary Outcome Measure Information:

Title

Sequential organ failure assessment (SOFA score)

Description

Increase in SOFA score is associated with worse outcome.

Time Frame

Change from baseline SOFA score at five days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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: 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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mona M El-Tamalawy, Master

Phone

01220650700

mona.m.eltamalawy@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mamdouh M El-Shishtawy, Professor

Organizational Affiliation

Faculty of Pharmacy-Mansoura University

Official's Role

Study Chair

Facility Information:

Facility Name

Tanta University Hospital

City

Tanta

State/Province

EL-Gharbia

ZIP/Postal Code

31527

Country

Egypt

Individual Site Status

Recruiting

Facility Contact:

Phone

1220650700

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35330830

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.

Results Reference

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Adjuvant Use of Neostigmine in Sepsis and Septic Shock.

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