| 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
|
|
|
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
|
|
|
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
- 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).
- What additional supporting information will be shared?
Response - Study Protocol
- 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.
- For what types of analyses will this data be available?
Response - For individual participant data meta-analysis.
- By what mechanism will data be made available?
Response - Proposals should be directed to [doc.mounikareddy@gmail.com].
- 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.
- 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.
|