| CTRI Number |
CTRI/2024/09/073420 [Registered on: 05/09/2024] Trial Registered Prospectively |
| Last Modified On: |
03/09/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
To evaluate efficacy of combination therapy of norepinephrine and milrinone against epinephrine alone as a first-line agent in fluid refractory Pediatric septic shock for early resolution of shock in children aged 1 month to 18 years– a randomized controlled trial |
|
Scientific Title of Study
|
A combination therapy of norepinephrine and milrinone as a first-line agent in fluid refractory Pediatric 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 |
Man Singh Parihar |
| Designation |
Senior Resident |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Pediatrics, All India Institute of Medical sciences, Virbhadra Road, Rishikesh
Dehradun
UTTARANCHAL
249203
India |
| Phone |
8872381130 |
| Fax |
|
| Email |
dr.maansingh1986@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Lokesh Tiwari |
| Designation |
Professor |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Pediatrics, All India Institute of Medical sciences, Virbhadra Road, Rishikesh
Dehradun
UTTARANCHAL
249203
India |
| Phone |
9631638095 |
| Fax |
|
| Email |
lokeshdoc@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Lokesh Tiwari |
| Designation |
Professor |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Pediatrics, All India Institute of Medical sciences, Virbhadra Road, Rishikesh
Dehradun
UTTARANCHAL
249203
India |
| Phone |
9631638095 |
| Fax |
|
| Email |
lokeshdoc@yahoo.com |
|
|
Source of Monetary or Material Support
|
| ALL INDIA INSTITUTE OF MEDICAL SCIENCES, Virbhadra Road, Rishikesh
Dehradun
UTTARANCHAL
249203 India |
|
|
Primary Sponsor
|
| Name |
AIIMS RISHIKESH |
| Address |
Department of Pediatrics, Shivaji Nagar, Veerbhadra Road, AIIMS Rishikesh, 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 Man Singh Parihar |
All India Institute of Medical sciences, Rishikesh |
Department of Pediatrics, All India Institute of Medical sciences, Virbhadra Road, Rishikesh
Dehradun
UTTARANCHAL |
8872381130
dr.maansingh1986@gmail.com |
|
|
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 |
Combination therapy of Norepinephrine and Milrinone infusion |
Combination therapy of Norepinephrine and Milrinone will be used as a first line inotropic agent in fluid refractory Pediatric Septic shock in one arm. Norepinephrine plus Milrinone, the combination therapy will be started at the minimum recommended dose of both the drugs, i.e., Norepinephrine at 0.05 mcg/kg/min and milrinone at 0.25 mcg/kg/min. If therapeutic endpoints of shock are not achieved, the dose of the drugs will be increased gradually depending on the physiological status. If the child remains in hypotensive shock, Norepinephrine will be increased gradually to the maximum dose of 0.3 mcg/kg/min every 15 minutes. If the BP is maintained, but signs of poor perfusion persist, Milrinone will gradually increase to the maximum dose of 0.75 mcg/kg/min. Primary outcome will be achievement of all therapeutic end points of shock at 6 hours of therapy. After reaching the maximum doses of both or one of the inotropes, if therapeutic endpoints are not achieved, the treatment will be labeled as refractory to combination therapy. Subsequent management will be as per the surviving sepsis campaign international guidelines for catecholamine refractory shock.
|
| Comparator Agent |
Epinephrine infusion |
Epinephrine will be used as a first line inotropic agent in fluid refractory Pediatric Septic shock in another arm. In the epinephrine group, the standard therapy, the drug will be started at the recommended minimum dose of 0.05 mcg/kg/min. The child will be continuously monitored with clinical and laboratory parameters. If the therapeutic endpoints are not achieved within 15 minutes of starting the drug, the drug dose will be increased gradually every 15 minutes with continuous monitoring to the maximum dose of 0.3 mcg/kg/min. Primary outcome will be achievement of all therapeutic end points of shock at 6 hours of therapy. Even after the child has received the maximum dose of the intervention drug and does not achieve therapeutic endpoints, the treatment will be labeled as Epinephrine refractory, and the child will be started on other vasoactive agents as per the hemodynamic status. If, at any point, BP is normalized, but other signs of poor perfusion persist, then the child will be started on Milrinone as per the pediatric surviving sepsis campaign international guidelines. |
|
|
Inclusion Criteria
|
| Age From |
1.00 Month(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
Children aged one month to 18 years with septic shock, defined as children with suspect or confirmed sepsis and cardiovascular dysfunction, who are fluid refractory, defined as the persistence of features of poor perfusion even after 40 ml/kg of fluid boluses or having clinical features of fluid overload |
|
| ExclusionCriteria |
| Details |
1. Children with Fulminant myocarditis
2. Children with Congenital heart disease, cardiomyopathy
3. Children already on inotropes at the time of enrolment |
|
|
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 proportion of children attaining shock resolution (achieving all therapeutic endpoints of shock) at 6 hours |
Six hours |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. Proportion of children achieving therapeutic endpoints at 1st and 24 hours of resuscitation
2. All-cause mortality at discharge or day 28 (whichever is earlier) and duration of PICU stay
3 . Occurrence of adverse events, i.e., tachycardia, tachyarrhythmia (Paroxysmal ventricular tachycardia, ventricular tachycardia, ventricular fibrillation), lactic acidosis, acute kidney injury, digital ischemia (gangrene, peripheral mottling)
4. Maximum Vasoactive inotrope score on days 1, 2, and 3 and duration of inotropes
5. PSOFA score and PELOD-2 score at 24, 48 and 72 hours. |
1.First and 24 hours
2.At discharge or at day 28 (whichever is earlier)
3. Occurrence of adverse events in 1st 72 hours
4. 72 hours
5.At 24, 48 and 72 hours
|
|
|
Target Sample Size
|
Total Sample Size="164"
Sample Size from India="164"
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
|
N/A |
|
Date of First Enrollment (India)
|
01/10/2024 |
| 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="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| 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
|
The RCT will evaluate the efficacy of a combination therapy of Norepinephrine and Milrinone as a first-line agent in fluid refractory pediatric septic shock resulting in shock reversal in a greater proportion of children compared to the use of Epinephrine alone in children age one month to 18 years Shock resolution is defined as attainment of all therapeutic endpoints as per surviving sepsis campaign international guidelines. |