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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  
Name  Address 
NIL  NIL 
 
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  
Status 
Not Applicable 
 
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.

 

In this context, our aim is to compare epinephrine and norepinephrine as first-line agents for shock among paediatric hematoncology patients.


 
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