| CTRI Number |
CTRI/2022/09/045180 [Registered on: 02/09/2022] Trial Registered Prospectively |
| Last Modified On: |
23/08/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug Process of Care Changes |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Comparison between adrenaline vs noradrenaline in children with cancer presenting with shock |
|
Scientific Title of Study
|
Efficacy of Epinephrine versus Nor-epinephrine as the initial vasoactive agent in Paediatric hematoncology patients with shock- A Feasibility Pilot study |
| Trial Acronym |
NEO study |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Ananya Sampath |
| Designation |
Senior registrar |
| Affiliation |
Apollo Hospitals, Chennai |
| Address |
D1, Dwaraka Apartments, 9/21, First Avenue, Shastrinagar, Adyar, Chennai PICU, first floor,
Apollo Multispecialty hospital
Teynampet
Chennai Chennai TAMIL NADU 600020 India |
| Phone |
09986261009 |
| Fax |
|
| Email |
ananya.sampath92@gmail.com |
|
Details of Contact Person Scientific Query
|
| Name |
Dr Indira Jayakumar |
| Designation |
Senior Consultant |
| Affiliation |
Apollo Hospitals, Chennai |
| Address |
Q101
The Atrium
22, Kalakshetra Road
Thiruvanmiyur Apollo Multispecialty hospital
Teynampet
Chennai Chennai TAMIL NADU 600041 India |
| Phone |
09710925667 |
| Fax |
|
| Email |
indirajayakumar@yahoo.com |
|
Details of Contact Person Public Query
|
| Name |
Dr Ananya Sampath |
| Designation |
Senior registrar |
| Affiliation |
Apollo Hospitals, Chennai |
| Address |
PICU, First floor,
Apollo Multispeciality hospital
teynampet
Chennai Apollo Multispecialty hospital
Teynampet
Chennai Chennai TAMIL NADU 600020 India |
| Phone |
09986261009 |
| Fax |
|
| Email |
ananya.sampath92@gmail.com |
|
|
Source of Monetary or Material Support
|
| Apollo Hospitals, Chennai |
|
|
Primary Sponsor
|
| Name |
Apollo Hospitals |
| Address |
Apollo Hospitals,
Teynampet
Chennai |
| 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 Ananya Sampath |
Apollo Hospital |
PICU, First floor,
Chennai TAMIL NADU |
9986261009
ananya.sampath92@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| ARI |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: R031||Nonspecific low blood-pressure reading, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Epinephrine |
Inotrope when cardiac dysfunction is causing shock
as continuous iv infusion at 0.05-0.2mcg/kg/min till resolution of shock |
| Comparator Agent |
Norepinephrine |
Pressor agent if sepsis is the reason for shock as continuous intravenous infusion at
0.05-0.2mcg/kg/min till resolution of shock |
| Intervention |
Start of study drug for shock |
After adequate fluid resuscitation either of the two drugs are started and clinical status assessed |
|
|
Inclusion Criteria
|
| Age From |
1.00 Month(s) |
| Age To |
17.00 Year(s) |
| Gender |
Both |
| Details |
Hematoncology patients aged 1 month to 17 years with early shock, defined as children with unresolved shock/hypoperfusion after the initial 10- 20ml/kg fluid bolus. |
|
| ExclusionCriteria |
| Details |
1. Children with fulminant myocarditis
2. Children with established, untreated heart disease
3. Parents not willing to participate in the study
4. Caregiver/Physician unwilling for patient to be enrolled
5. Post-arrest shock
6. Moribund patients in whom anticipated survival < 24 hrs (since many are in recalcitrant downward spiral of overall condition where the impact of one or other vasoactive may be difficult to assess).
|
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
Pharmacy-controlled Randomization |
|
Blinding/Masking
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Pilot study to assess feasibility for randomized control trial enrolment, adherence to trial protocol and follow up with respect to resolution of shock in hematoncology patients aged 1 month to 17 years with early undifferentiated shock. |
1. Fluid requirement in 0-6 hours and 6-24 hours
2. Vasoactive-inotrope score at 6 hours
3. Days alive and free of organ support (ventilator support, Renal replacement therapy) up to 28-days
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To determine the choice of first vasoactive agent between epinephrine and norepinephrine in pediatric hematoncology patients with undifferentiated shock |
1. Fluid requirement in 0-6 hours and 6-24 hours
2. Vasoactive-inotrope score at 6 hours
3. Days alive and free of organ support (ventilator support, Renal replacement therapy) up to 28-days
|
|
|
Target Sample Size
|
Total Sample Size="100" Sample Size from India="100"
Final Enrollment numbers achieved (Total)= "150"
Final Enrollment numbers achieved (India)="150" |
|
Phase of Trial
|
Phase 3/ Phase 4 |
|
Date of First Enrollment (India)
|
10/09/2022 |
| Date of Study Completion (India) |
19/05/2024 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1" Months="0" Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
Efficacy of Epinephrine versus Nor-epinephrine as the initial vasoactive agent in Paediatric hematoncology patients with shock- A Feasibility Pilot study(NEOSTUDY) |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
There are thought to be key differences in pathophysiology of shock in children compared to adults. Unlike adults who usually have a compensatory mechanism to maintain adequate cardiac output, children often exhibit a “low cardiac output†state secondary to severe myocardial depression. (1) Early manifestations of shock in children include tachycardia, cold peripheries, prolonged CFT, narrow pulse pressure and late signs include altered mental status and hypotension. Early recognition of shock and appropriate interventions are associated with favourable outcomes (2-5). Management of a child in shock includes optimizing the macro- and micro-circulation. Fluid therapy constitutes the first step in the management of a child in shock (16). Though correcting hypovolemia is important, the risk of fluid overload is to be borne in mind as this can lead to worse outcomes (6). After initial fluid resuscitation, if a child continues to be in shock and is determined not to be fluid responsive or the benefits of giving further fluids are going to be counterproductive, one needs to optimise cardiac output by improving the cardiac contractility and/or attempting to normalize the systemic vascular resistance. Inotropes and vasoactive drugs need to be optimised from this point onwards to achieve shock resolution (7, 8). Vasoactive drugs include vasopressors and vasodilators. As inotropes increase the contractility, Inodilators are another class of drugs that improve both contractility and cause systemic vasodilation (7). Dopamine has long been used as a first line inotrope of choice in paediatric shock (7,8). Recent evidence, including an Indian trial has shown that dopamine is associated with more tachyarrhythmias and increased incidence of health care associated infections and higher mortality (9, 10). The most recent paediatric Surviving Sepsis Guidelines (pSSC) 2020 recommends one of 2 catecholamines, viz, epinephrine or norepinephrine as the first line vasoactive-inotrope in paediatric fluid refractory shock (10), based on the caregiver’s decision. Further, the pSSC has de-emphasized cold vs warm shock pathway, considering evidence (11,2) showing that even with overt cold shock, a vasodilatory state can exist with wide pulse pressures, decreased SVR and increased cardiac index. Regarding epinephrine versus norepinephrine; both are found to be equally efficacious with epinephrine reported to cause more drug related side effects in adult patients (12-14). However, the majority of these reports are derived from adult studies and it is important to note that there are no published studies comparing the epinephrine vs norepinephrine in children till date. Cardiac dysfunction is relatively common in oncology patients admitted in PICU with shock that leads to higher risk of morbidity and mortality in these children (1). The cardiac dysfunction in these children can be due to lot of reasons including underlying hematologic/oncologic condition, chemotherapeutic agents, bone marrow transplantation, cytokine release syndrome. This also makes this subset of children different from the other paediatric patients. |