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CTRI Number  CTRI/2024/10/075496 [Registered on: 18/10/2024] Trial Registered Prospectively
Last Modified On: 17/10/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Medical Device
Diagnostic
Process of Care Changes 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Comparing a New Non-Invasive Monitoring Method with Standard Care in Children with Severe Infection-Related Shock: A Pilot Study 
Scientific Title of Study   Continuous non-invasive advanced hemodynamic monitoring versus standard care for the management of pediatric septic shock - A pilot randomized control 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 Mounika Vadhi Reddy 
Designation  Assistant Professor 
Affiliation  All India Institute of Medical Sciences Bibinagar 
Address  Pediatric Intensive Care Unit, Department of Pediatrics, All India Institute of Medical Sciences Bibinagar, Warangal highway, Yadadri Bhuvanagiri District, Telangana

Hyderabad
TELANGANA
508126
India 
Phone  9855784739  
Fax    
Email  doc.mounikareddy@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Mounika Vadhi Reddy 
Designation  Assistant Professor 
Affiliation  All India Institute of Medical Sciences Bibinagar 
Address  Pediatric Intensive Care Unit, Department of Pediatrics, All India Institute of Medical Sciences Bibinagar, Warangal highway, Yadadri Bhuvanagiri District, Telangana

Hyderabad
TELANGANA
508126
India 
Phone  9855784739  
Fax    
Email  doc.mounikareddy@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Mounika Vadhi Reddy 
Designation  Assistant Professor 
Affiliation  All India Institute of Medical Sciences Bibinagar 
Address  Pediatric Intensive Care Unit, Department of Pediatrics, All India Institute of Medical Sciences Bibinagar, Warangal highway, Yadadri Bhuvanagiri District, Telangana

Hyderabad
TELANGANA
508126
India 
Phone  9855784739  
Fax    
Email  doc.mounikareddy@gmail.com  
 
Source of Monetary or Material Support  
Anusandhan National Research Foundation (ANRF) Science and Engineering Research Board (SERB) Department of Science and Technology (DST) 3rd & 4th Floor, Block II, Technology Bhawan, New Mehrauli Road New Delhi - 110 016, India 
 
Primary Sponsor  
Name  Mounika Reddy 
Address  Department of Pediatrics, AIIMS Bibinagar, Warangal highway, Yadadri Bhuvanagiri District, Telangana 
Type of Sponsor  Other [Self] 
 
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 Mounika Reddy  All India Institute of Medical Sciences, Bibinagar  Pediatric Intensive care Unit, Department of Pediatrics
Nalgonda
TELANGANA 
9855784739

doc.mounikareddy@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
AIIMS BBN- Insitutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: R652||Severe sepsis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Continuous non-invasive cardiac output monitor  The subjects randomized to the intervention arm will be connected to the portable hand- held continuous non-invasive cardiac output monitor continuously for the first 48 hours of their management, which will provide continuous measurements of cardiac output, stroke volume variability, systemic vascular resistance, index of contractility and thoracic fluid content. These values along with the other standard clinical monitoring would be used to guide the selection of vasoactive agent, fluid bolus and further management of the patients. Those with high cardiac index and low systemic vascular resistance will receive vasopressors like noradrenaline and vasopressin. Those with low cardiac index and high systemic vascular resistance will receive inotropes like adrenaline and inodilators like milrinone. If the stroke volume variability is more than 12%, further fluid bolus may be considered if there are no other features of fluid overload. The duration of vasoactive-inotrope support and need for fluid boluses will depend on the clinical status of the patient, and will be decided by the treatment clinician.  
Comparator Agent  Standard care  In the standard arm, patients will be managed as per institutional protocols of septic shock management based on latest international guidelines. Standard monitoring includes clinical assessment, continuous invasive arterial blood pressure monitoring and bedside focused echocardiography to assess volume status and cardiac contractility. Patients will receive 40-60 ml/kg fluid bolus prior to initiating vasoactives. Treating clinicians can escalate therapy as clinically indicated with further fluid boluses or additional vasoactives/inotropes. 
 
Inclusion Criteria  
Age From  2.00 Month(s)
Age To  18.00 Year(s)
Gender  Both 
Details  Children aged 2 months to 18 years with early septic shock, defined as children with
suspect or confirmed sepsis and unresolved shock or hypoperfusion after the initial 20ml per kg fluid bolus or 1000 ml fluid bolus in patients weighing over 50 kg, received within last 4 hours 
 
ExclusionCriteria 
Details  Exclusion criteria:
- Preterm babies with corrected age less than 2 months
- Children with fulminant myocarditis or cardiomyopathy
- Children with unrepaired congenital heart disease or cardiac failure
- Children with severe acute malnutrition
- Known chronic renal failure defined as requiring renal replacement therapy
- Known chronic hepatic failure
- Already on inotropes for more than 2 hours
- Suffered cardiorespiratory arrest within less than 2 hours requiring cardiopulmonary resuscitation
of more than 2 mins duration
- Moribund patients with anticipated survival less than 24 hrs
- Not willing to participate in the study 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To evaluate the difference between the two groups in terms of survival free of organ dysfunction  At 28 days 
 
Secondary Outcome  
Outcome  TimePoints 
Time to achieve therapeutic end-points of shock resolution  till discharge 
Fluid overload percentage  24, 48 and 72 hours 
Length of PICU stay and hospital stay  till discharge 
Early and late mortality  7 and 28 day 
Physiological markers including lactate - Inotropes, ventilation, other organ support  till discharge 
 
Target Sample Size   Total Sample Size="60"
Sample Size from India="60" 
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)   28/10/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  28/10/2024 
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)  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 - YES
  1. What data in particular will be shared?
    Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

  2. What additional supporting information will be shared?
    Response -  Study Protocol

  3. Who will be able to view these files?
    Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.

  4. For what types of analyses will this data be available?
    Response - For individual participant data meta-analysis.

  5. By what mechanism will data be made available?
    Response - Proposals should be directed to [doc.mounikareddy@gmail.com].

  6. For how long will this data be available start date provided 01-01-2026 and end date provided 01-01-2031?
    Response - Beginning 3 months and ending 5 years following article publication.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - nil
Brief Summary  

Septic shock is a leading cause of childhood morbidity and mortality. Pathophysiology includes a combination of fluid depletion, heterogenous vasodilatation, capillary leak and myocardial dysfunction, with varying contributions over time. Accurate hemodynamic assessments are necessary to guide therapy (including fluids, vasoactives, inotropes) and traditional clinical monitoring is not accurate enough. Invasive cardiac output monitoring with pulmonary artery catheter, though believed to be gold standard, is associated with significant risks and is not routinely employed. Continuous non-invasive advanced hemodynamic monitoring based on electrical cardiometry has been validated in children and adults. However, whether it will provide better real-time guidance regarding pediatric septic shock management as compared to current standard care, to facilitate optimal fluid administration and/or drug titrations for time-sensitive, goal directed resuscitation is not known, and whether this will translate into better patient-centered outcomes like reduced mortality and morbidity has not been studied. Hence we designed this pilot open-label, parallel-arm, randomized control trial. We hypothesize that a protocol on continuous non-invasive advanced hemodynamic monitoring to guide management of pediatric septic shock is feasible and that the intervention will lead to lesser organ dysfunction, earlier shock resolution and better patient outcomes as compared to current standard management. Our feasibility objectives include determination of recruitment, consent, treatment protocol adherence and retention/follow-up rates. Primary clinical objective is survival free of organ dysfunction censored at 28 days. Other objectives include comparison of mortality, time to shock resolution, organ supports, fluid overload and long-term functional outcomes and quality of life between the two groups. We would randomize 60 children (30 in each arm, with 1:1 ratio), aged 2 months – 18 years with diagnosis of septic shock, unresolved after initial 20ml/kg isotonic fluid bolus. Those in the intervention arm would be connected to continuous non-invasive advanced hemodynamic monitor based on electrical cardiometry, which will provide measurements of cardiac output, stroke volume variability, systemic vascular resistance, index of contractility and thoracic fluid content. There measures along with standard clinical monitoring would be used to guide further fluid bolus, selection and titration of vasoactive agents. Those in the control arm will be managed as per standard institutional protocols. All the patients will be followed up to 28 days or death, whichever is earlier and then at 6 months to study outcomes. The study findings may facilitate better understanding of pediatric septic shock phenotypes, response to treatment, and will inform a future larger multicenter trial. Institute ethics approval will be sought and informed consent will be obtained from all participants. 

 
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