| CTRI Number |
CTRI/2024/08/072434 [Registered on: 13/08/2024] Trial Registered Prospectively |
| Last Modified On: |
08/08/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Two different medicines named Methylene blue and vasopressin will be compared as second line blood pressure raising medication in patients having infection with low blood pressure |
|
Scientific Title of Study
|
Methylene blue Versus Vasopressin as Second Line Vasopressor in Septic Shock- A 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 Ravinder Kumar Pandey |
| Designation |
Professor |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
Department of Anaesthesiology, Teaching block 5th floor, AIIMS, Ansari Nagar East, New Delhi-110029
New Delhi
DELHI
110029
India |
| Phone |
9773500767 |
| Fax |
|
| Email |
ravindrapandey1972@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Ravinder Kumar Pandey |
| Designation |
Professor |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
Department of Anaesthesiology, Teaching block 5th floor, AIIMS, Ansari Nagar East, New Delhi-110029
DELHI
110029
India |
| Phone |
9773500767 |
| Fax |
|
| Email |
ravindrapandey1972@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Kathiravan T |
| Designation |
Senior resident |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
Department of Anaesthesiology, Pain medicine and critical care, Room no-5011, 5th floor, Teaching block, AIIMS, Ansari nagar
New Delhi
DELHI
110029
India |
| Phone |
9486649488 |
| Fax |
|
| Email |
kathiravan4763@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute Of Medical Sciences, New Delhi-110029 |
|
|
Primary Sponsor
|
| Name |
All India Institute Of Medical Sciences New Delhi |
| Address |
AIIMS, Sri Aurobindo Marg, Ansari nagar, New delhi, Delhi-110029, India |
| 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 Kathiravan T |
All India institute of medical sciences |
AB8 ICU, 8 TH FLOOR, WARD BLOCK, Department of Anaesthesiology, Pain medicine and critical care
New Delhi
DELHI |
9486649488
kathiravan4763@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institute Ethics committee, AIIMS, NEW DELHI |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: I958||Other hypotension, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
GROUP M |
Methylene blue 1 mg/kg intravenous bolus followed by 0.25 mg/kg/hour Intravenous infusion. The infusion will be continued for 96 hours or till the requirement of norepinephrine is less than 0.1 micg/kg/min, whichever is earlier |
| Comparator Agent |
GROUP V |
Vasopressin infusion of 0.03 U/Kg/hr. Infusion will be continued till the requirement of norepinephrine is less than 0.1 micg/kg/min |
|
|
Inclusion Criteria
|
| Age From |
16.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
Adult patients with septic shock requiring norepinephrine support of ≥0.2 µg/kg/min for a minimum of 30 minutes despite fluid resuscitation with a minimum of 20 ml/kg to maintain mean arterial pressure (MAP) ≥65 mm Hg |
|
| ExclusionCriteria |
| Details |
1.Patients with allergy to methylene blue
2.Patients with known Glucose-6-phosphate dehydrogenase (G6PD) deficiency
3.Patients with familial history of G6PD deficiency
4.Patients with known haemolytic anaemia
5.Patients with severe acute respiratory distress syndrome (ARDS)
6.Pregnant and lactating women
7.Patients with concurrent haemorrhagic or obstructive shock
8.Patients with acute kidney injury KDIGO grade 3, pre-existing chronic renal disease
9.Patients with pre-existing chronic liver disease
10.Patients with coronary artery disease
11.Patients on MAO inhibitors and selective serotonin re-uptake inhibitors
12.Patients who have already been administered either of the two study drugs at any point during the disease
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| The difference in the average sequential organ failure assessment (SOFA) score at day 7 |
The difference in the average sequential organ failure assessment (SOFA) score at day 7 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. Duration of requirement of vasopressors
2. Vasopressor- free days (number of days alive and free of vasopressors at day 30)
3.Ventilator-free days (number of days alive and free of mechanical ventilator at day 30)
4. Renal replacement therapy free days (number of days alive and free of renal replacement therapy at day 30)
5. Lactate levels
6. Incidence of acute kidney injury (AKI)
7. ICU- free days ( number of days alive and out of the ICU at day 30)
8. ICU mortality, hospital mortality or any cause mortality at day 30. |
Day 30 |
|
|
Target Sample Size
|
Total Sample Size="92"
Sample Size from India="92"
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
|
Phase 3/ Phase 4 |
|
Date of First Enrollment (India)
|
19/08/2024 |
| 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="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
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
|
Adult patients with septic shock requiring norepinephrine support of ≥0.2
µg/kg/min for a minimum of 30 minutes despite fluid resuscitation with a
minimum of 20 ml/kg to maintain mean arterial pressure (MAP) ≥65 mm Hg will be randomly allocated into group M or V. Patients randomized to group M will receive
a bolus of 1 mg/kg methylene blue over 15 minutes followed by an infusion of
0.25 mg/kg/hr. If there is improvement in MAP and the requirement of
norepinephrine is reduced to <0.1 µg/kg/min, methylene blue infusion will be
stopped. In case of worsening and norepinephrine requirement increases to >
0.4µg/kg/min, other vasopressors like vasopressin or adrenaline will be started
as per ICU physician discretion in addition to methylene blue infusion.
Methylene blue infusion will be continued for 96 hours or till the
norepinephrine requirement reduces to <0.1 µg/kg/min whichever is
earlier. Patient randomised to group V
will receive vasopressin infusion of 0.03 U/kg/hr. If there is improvement in
MAP and the requirement of norepinephrine is reduced to <0.1 µg/kg/min,
vasopressin infusion will be stopped. In case of worsening and norepinephrine
requirement increases to > 0.4µg/kg/min, other vasopressor like adrenaline
will be started and vasopressin dose titrated as per ICU physician discretion. Methylene blue or Vasopressin will be continued till the norepinephrine
requirement reduces to <0.1 µg/kg/min. Beyond this period, the decision to
continue methylene blue will be left to the discretion of the treating
intensivist. Methylene blue will be discontinued if patient develops severe
impairment in oxygenation (PaO2/FiO2 less than 100 mm Hg), KDIGO stage III
acute kidney injury, haemolysis, or in patients in whom symptoms suggestive of
serotonin syndrome. Apart from this, methylene blue will be discontinued at any
point of time by the treating intensivist if it is felt that methylene blue
therapy is harming the patient. Patients, in whom the study drug must be
discontinued at any point of time for the above reasons, they will still be
considered a part of study and data collection is continued. In case, if
consent is withdrawn after enrolment, any intervention related to the study
drug will be discontinued, and the patient will be omitted from analysisThe point of enrolment will be taken as time = 0. The following data
sets will be recorded at the specified time intervals:
a)
Enrolment
data: Demographic and
anthropometric data, ICU severity of illness scores, probable source of sepsis
and volume of fluid received in the preceding 24 hours will be recorded at
enrolment.
b)
Organ
function data: PaO2/FiO2,
serum creatinine, bilirubin and SOFA score will be recorded at the time
of enrolment and every 24 hours for 7 days. The average SOFA score will be
taken as the primary outcome.
c)
Hemodynamic
data: Heart rate, MAP
and vasopressor requirements will be recorded every 6 hours from enrolment up to
96 hours. CVP, cardiac index, SVRI, and fluid intake (sum of enteral and
intravenous fluid intake) will be recorded every 12 hours from enrolment up to
96 hours.
d)
Oxygenation
and micro-circulatory function data: Haemoglobin, arterial oxygen saturation (SaO2), ScvO2,
peripheral oxygen extraction ration (O2ER), base excess (BE) and arterial
lactate levels will be recorded every 12 hours from enrolment up to 96 hours
e)
Myocardial
performance data: LVEF,
E/e’ ratio and TAPSE will be recorded every 12 hours from enrolment up to 96
hours. TnI will be measured at enrolment and at 96 hours.
Patients will be
followed up to 30 days after enrolment. Number of days on mechanical
ventilation, need for renal replacement therapy, length of ICU stay, duration
of survival and serious adverse events – including, but not limited to
haemolysis, worsening hypoxemia, acute kidney injury, severe hepatic impairment
will be recorded. |