Sepsis, Septic ShockPhase 2NCT04130230
Adjuvant Use of Neostigmine in Sepsis and Septic Shock.
A Phase 2 study testing Neostigmine and Standard therapy in people with Sepsis, Septic Shock, run by Mansoura University at 1 site in Egypt.
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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Sepsis, Septic Shock
- What is being tested?
- Neostigmine and Standard therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteEgypt
- Study dates
- 6 Mar 2019to 1 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Efficacy of Neostigmine Infusion as Adjuvant Therapy in Sepsis and Septic Shock
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
- Being tested
- Neostigmine, Standard therapy
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeostigmineDrug
Also called Choline esterase inhibitor
Neostigmine continuous infusion plus standard therapy for sepsis and septic shock.
Standard therapyDrug
Standard therapy for sepsis and septic shock
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Neostigmine |
| Standard group | Placebo comparator | This arm will receive the standard therapy for sepsis and septic shock only and followed for five days. Receives: Drug: Standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sequential organ failure assessment (SOFA score)
Increase in SOFA score is associated with worse outcome.
Measured: Change from baseline SOFA score at five days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2019
- Study start6 Mar 2019
- Primary completion10 Aug 2021
- Study completion1 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sepsis, Septic ShockStudies of the same condition, open and under way.
- More trials run by Mansoura UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mansoura University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mona Mohammed El-Tamalawy, Mansoura University
- Investigators
- Mamdouh M El-Shishtawy, Professor, Study chair, Faculty of Pharmacy-Mansoura University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04130230
- Sponsor's protocol ID
- 2019-3
- Status last verified
- Jul 2024
- First submitted
- 8 Oct 2019
- Last updated
- 10 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35330830
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Neostigmine Infusion as Adjuvant Therapy in Sepsis and Septic Shock
- ClinicalTrials.gov ID
- NCT04130230
- Acronym / sponsor ID
- 2019-3
- Conditions
- Sepsis, Septic Shock
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Mansoura UniversityUniversity, hospital or other
- Study start
- 6 Mar 2019 (actual)
- Primary completion
- 10 Aug 2021 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 17 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neostigmine group | Experimental | Drug: NeostigmineThis 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. |
| Standard group | Placebo comparator | Drug: Standard therapyThis arm will receive the standard therapy for sepsis and septic shock only and followed for five days. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeostigmineAlso: Choline esterase inhibitorNeostigmine continuous infusion plus standard therapy for sepsis and septic shock. | Drug | Neostigmine group |
| Standard therapyStandard therapy for sepsis and septic shock | Drug | Standard group |
Primary outcome
Sequential organ failure assessment (SOFA score)
Time frame: Change from baseline SOFA score at five days
Increase in SOFA score is associated with worse outcome.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Derived from this study: PubMed 35330830El-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mamdouh M El-Shishtawy, Professor study chair
Faculty of Pharmacy-Mansoura University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neostigmine and Standard therapy in people with Sepsis, Septic Shock, run by Mansoura University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sequential organ failure assessment (SOFA score) (time frame: Change from baseline SOFA score at five days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04130230, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.