| CTRI Number |
CTRI/2025/01/079070 [Registered on: 20/01/2025] Trial Registered Prospectively |
| Last Modified On: |
20/01/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Other (Specify) [Adjuvant therapy] |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Role of Neostigmine in patients severe infection with low blood pressure |
|
Scientific Title of Study
|
Effect of Neostigmine on outcomes in patients with Septic Shock: A Double-blind Randomized Controlled Trial |
| Trial Acronym |
Nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Deepak Singla |
| Designation |
Additional Professor |
| Affiliation |
AIIMS Rishikesh |
| Address |
Room No 016133 Department of Anaesthesiology All India Institute of Medical Sciences Rishikesh Virbhadra Road Rishikesh Uttarakhand
Dehradun
UTTARANCHAL
249204
India |
| Phone |
9068504999 |
| Fax |
|
| Email |
deepak10.4u@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Prof Gaurav Jain |
| Designation |
Professor |
| Affiliation |
AIIMS Rishikesh |
| Address |
Room No 016127 Department of Anaesthesiology All India Institute of Medical Sciences Rishikesh Virbhadra Road Rishikesh Uttarakhand
Dehradun
UTTARANCHAL
249204
India |
| Phone |
8808631209 |
| Fax |
|
| Email |
icubhu@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Deepak Singla |
| Designation |
Additional Professor |
| Affiliation |
AIIMS Rishikesh |
| Address |
Room No 016133 Department of Anaesthesiology All India Institute of Medical Sciences Rishikesh Virbhadra Road Rishikesh Uttarakhand
Dehradun
UTTARANCHAL
249204
India |
| Phone |
9068504999 |
| Fax |
|
| Email |
deepak10.4u@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences Rishikesh |
|
|
Primary Sponsor
|
| Name |
All India Institute of Medical Sciences Rishikesh |
| Address |
Veerbhadra Road Near Barrage Sturida Colony Pahsulok Rishikesh Uttarakhand 249203 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Deepak Singla |
AIIMS Rishikesh |
Room No 016133 Department of Anaesthesiology All India Institute of Medical Sciences Rishikesh Virbhadra Road Rishikesh Uttarakhand
Dehradun
UTTARANCHAL |
9068504999
deepak10.4u@gmail.co m |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee AIIMS Rishikesh |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: R652||Severe sepsis, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Neostigmine infusion |
2.0 ml/hr for 5 days |
| Comparator Agent |
Saline infusion |
2.0 ml/hr for 5 days |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
Adult patients who are admitted to the ICU with septic shock of less than 24-hour duration |
|
| ExclusionCriteria |
| Details |
Patients who refuse to consent for the study.
Patients with SOFA score of 6 or more.
Patients with asthma, bradycardia or heart block, head injury, muscle dystrophy, urinary or gastrointestinal obstruction.
Pregnant patients or lactating mothers
Patients with known allergy to neostigmine. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| SOFA score |
Day five post ICU admission |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Relative change in SOFA score (deltaSOFA) from baseline |
Day five post ICU admission |
| Ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) |
Day 0(baseline), 3, 5 and 7 post ICU admission |
| GCS score |
Day 0(baseline), 3, 5 and 7 post ICU admission |
| Reversal of shock |
Day 3, 5 and 7 post ICU admission |
| Need for mechanical ventilation |
Day 0(baseline), 3, 5 and 7 post ICU admission |
| Successful extubation |
Day 3, 5 and 7 post ICU admission |
| Mortality |
28 days post ICU admission |
| Length of ICU stay |
28 days post ICU admission |
| Length of hospital stay |
28 days post ICU admission |
| Complications |
Day five post ICU admission |
|
|
Target Sample Size
|
Total Sample Size="64"
Sample Size from India="64"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Post Marketing Surveillance |
|
Date of First Enrollment (India)
|
01/04/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Though fluid resuscitation remains the first line therapy for management of hypotension including the one associated with sepsis. Overjealous use of fluids can lead to venous congestion, raised central venous pressure which can impair the microcirculatory blood flow thus reducing tissue perfusion. The surviving sepsis 2021 guidelines have also downgraded the recommendation of giving 30 ml/kg of crystalloids, from ‘Strong’ to ‘Weak’ with low quality of evidence. Recent data has shown that early initiation of vasopressors in patients with sepsis is associated with decreased mortality. Noradrenaline is the vasopressor of choice in patients with septic shock. It is more potent than dopamine and has a lower incidence of arrythmias. However, a high dose of noradrenaline is associated with decreased lactate clearance and makes lactate an unreliable marker for tissue perfusion. Vagus nerve was identified to play an anti-inflammatory role in patients with gram negative endotoxemia. The cholinergic anti-inflammatory pathway (CAP) attenuates systemic inflammatory response with nicotinic acetylcholine receptor as a main target. This inflammatory modulation might have therapeutic applications in patients with infection or inflammatory conditions of lungs. In humans, pyridostigmine has been used for treatment of septic shock caused by intra-abdominal infection. The study found that the use of physostigmine will cause a reduction in the noradrenaline requirement however the SOFA score were not significantly different between the two groups (physostigmine vs placebo). A recent study using neostigmine found it to significantly improve SOFA scores in patients with sepsis. However it also involved only 45 postsurgical patients and could not find a statistically significant difference in SOFA scores among patients with septic shock. So, currently the role of neostigmine in improving outcomes in patients with septic shock is still debatable. Therefore we plan this randomised controlled trial to study the effect of neostigmine infusion on outcomes in adult patients with septic shock. |