Management of Shock in Children With SAM or Severe Underweight and Diarrhea

December 18, 2022 updated by: International Centre for Diarrhoeal Disease Research, Bangladesh

Randomized Controlled Trial of Dopamine, Adrenaline, and Blood Transfusion for Treatment of Fluid Refractory Shock in Children With Severe Acute Malnutrition or Severe Underweight and Cholera or Other Dehydrating Diarrheas

Diarrhea is one of the leading causes of under-five childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. The coexistence of sepsis and hypovolemic shock in children with severe acute malnutrition (SAM) having diarrhea is common. At Dhaka hospital of icddr,b, the death rate is as high as 40% and 69% in children with severe sepsis and septic shock respectively with co-morbidities such as severe malnutrition.

The conventional management of SAM children with features of severe sepsis recommended by WHO includes administration of boluses of isotonic saline followed by blood transfusion in unresponsive cases with septic shock; whereas the Surviving Sepsis Campaign (SSC) guideline recommends vasoactive support. To date, no study has evaluated systematically the effects of inotrope(s) and vasopressor or blood transfusion in children with dehydrating diarrhea (for example, in cholera) and SAM having shock and unresponsive to WHO standard fluid therapy.

This randomized trial will generate evidence whether inotrope and vasopressor or blood transfusion should be selected for severely malnourished children having hypotensive shock and who failed to respond to WHO standard fluid bolus.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

  1. Burden: Burden: Diarrhea is one of the leading causes of under-five childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. Co-morbidity of severe acute malnutrition (SAM) and shock in children with diarrhea is associated with increased mortality. Nearly half of the patients admitted to the Intensive Care Unit (ICU) of Dhaka Hospital of icddr,b present with sepsis. Data demonstrates that about 43% of children progressed from severe sepsis to septic shock despite receiving recommended treatment. The death rate was found to be as high as 40% and 69% in children with severe sepsis and septic shock respectively with co-morbidities such as severe malnutrition.
  2. Knowledge gap: The conventional management of SAM children with features of severe sepsis recommended by WHO include administration of boluses of isotonic saline followed by blood transfusion in unresponsive cases with septic shock. However, a recent African study reported significantly higher mortality among children with features of severe sepsis when they were treated with boluses. To date, no study has evaluated systematically the effects of inotrope or vasopressor or blood transfusion in children with dehydrating diarrhea (for example, in cholera) and SAM having shock and unresponsive to WHO standard fluid therapy.
  3. Relevance: If this randomized trial signifies survival benefit from a blood transfusion, inotrope or vasopressor in the management of fluid refractory shock in children with severe acute malnutrition and cholera or other dehydrating diarrheas, then this approach would be a good candidate for implementation in the management of such children especially in developing countries

Hypothesis: We hypothesize that the death rates will be significantly lower in children with SAM or severe underweight, dehydrating diarrhea and fluid refractory shock who will be treated with dopamine or adrenaline compared to blood transfusion, after treatment failure with WHO standard bolus intravenous fluid therapy.

Objectives: To reduce mortality of the SAM or severely underweight children presenting with diarrhea and fluid refractory shock who will receive WHO standard fluid therapy followed by dopamine or adrenaline, compared to those receiving blood transfusion after WHO standard fluid therapy.

Methods: This will be a randomized, three-arm, controlled, non-masked clinical trial in children 1- 59 months old with SAM or severely underweight and fluid refractory shock. It will compare the efficacy of WHO-recommended fluid resuscitation followed by dopamine or adrenaline administration versus WHO recommended fluid resuscitation followed by blood transfusion. After parental written informed consent, children, in addition to usual supportive care, will be allocated to the study interventions following randomization.

Study Type

Interventional

Enrollment (Anticipated)

135

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Bangladesh
      • Dhaka, Bangladesh, 1000
        • Recruiting
        • Icddr,b
        • Contact:
        • Principal Investigator:
          • Tahmeed Ahmed, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 3 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Children of either sex with SAM or severe underweight and diarrhea
  2. Age: 1-59 months
  3. Children with cerebral palsy (CP) and/or developmental dealy
  4. Fluid refractory shock

Exclusion Criteria:

  1. Severe anemia (hemoglobin< 5 gm/dl) who will require a blood transfusion
  2. Sclerema
  3. Congenital anomalies (TOF/ASD/VSD/Trisomy 21, etc.)
  4. Having a rare blood group (negative blood groups)
  5. A child requiring cardio-pulmonary resuscitation during screening or having gasping respiration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dopamine arm
Children in the dopamine arm (Treatment plan A) will receive dopamine, 8 microgram/kg/min (increasing the dose after 15 minutes to 12 microgram/kg/min to a maximum of 15 microgram/kg/min)
Drug: Dopamine
Children will receive dopamine, 8 microgram/kg.min (increasing the dose after 15 minutes to 12 microgram/kg/min to a maximum of 15 microgram/kg/min)
Experimental: Adrenaline arm
Children in the adrenaline arm (Treatment plan B) will receive adrenaline, 0.1 microgram/kg/min (increasing the dose after 15 minutes to 0.2 microgram/kg.min to a maximum of 0.3 microgram/kg.min)
Drug: adrenaline
Children will receive adrenaline, 0.1 microgram/kg/min (increasing the dose after 15 minutes to 0.2 microgram/kg.min to a maximum of 0.3 microgram/kg.min)
Other Names:
  • Epinephrine
Active Comparator: Blood transfusion arm
Children in the blood transfusion arm (Treatment plan C) will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. While the blood transfusion is being arranged, IV fluid would be given @ of 3 ml per kg per hour
Drug: Blood Transfusion
Children will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. While the blood transfusion is being arranged, IV fluid would be given @ of 3 ml per kg per hour
Other Names:
  • Blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Case fatality rate
Time Frame: 28 days (± 3 days)
Number of mortalities among SAM or severe underweight children presenting with diarrhea and fluid refractory shock who would receive WHO standard fluid therapy followed by dopamine or adrenaline, compared to those receiving blood transfusion after WHO standard fluid therapy
28 days (± 3 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment failure rates
Time Frame: Through study completion, an average of 7 days
Number of children where we failed to achieve the goal of resuscitation after starting any one of the interventions
Through study completion, an average of 7 days
Need for mechanical ventilation
Time Frame: Through study completion, an average of 7 days
Number of children who would require mechanical ventilation
Through study completion, an average of 7 days
Heart failure
Time Frame: Through study completion, an average of 7 days
Number of children who developed heart failure. Heart failure will be assessed on the basis of - age-specific tachypnea, tachycardia, enlarged tender liver, pedal edema, basal crackles and/or gallop and response to furosemide (combination of findings).
Through study completion, an average of 7 days
Length of ICU stay
Time Frame: Through study completion, an average of 7 days
Time a child stays in ICU
Through study completion, an average of 7 days
Time-to-achieve recovery
Time Frame: 3-4 hours
Required times (minutes) for resuscitation of a child after randomization to a specific arms
3-4 hours
Left ventricular function of the study participants
Time Frame: Through study completion, an average of 7 days
Evaluation of left ventricular function (hyperdynamic or normal) by cardiac USG at enrollment, at time of heart failure (if any)
Through study completion, an average of 7 days
Right ventricular function of the study participants
Time Frame: Through study completion, an average of 7 days
Evaluation of right ventricular function (hyperdynamic or normal) by cardiac ultrasound at enrollment, at time of heart failure (if any)
Through study completion, an average of 7 days
Inferior vena cava collapsibility of the study participants
Time Frame: Through study completion, an average of 7 days
Evaluation of Inferior vena cava collapsibility by cardiac ultrasound at enrollment, at time of heart failure (if any)
Through study completion, an average of 7 days
Length of hospital stay
Time Frame: variable (days to months)
Time a child stays in the hospital
variable (days to months)
Mean arterial pressure (MAP) stabilization at 48 hours
Time Frame: 48 hours from the point of inclusion in the study
Number of children whose MAP was stabilized at 48 hours
48 hours from the point of inclusion in the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

International Centre for Diarrhoeal Disease Research, Bangladesh

Collaborators

University of British Columbia
Muhimbili University of Health and Allied Sciences

Investigators

  • Principal Investigator: Tahmeed Ahmed, PhD, International Centre for Diarrhoeal Disease Research, Bangladesh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 17, 2021

Primary Completion (Anticipated)

February 1, 2023

Study Completion (Anticipated)

April 1, 2023

Study Registration Dates

First Submitted

February 1, 2021

First Submitted That Met QC Criteria

February 7, 2021

First Posted (Actual)

February 11, 2021

Study Record Updates

Last Update Posted (Estimate)

December 20, 2022

Last Update Submitted That Met QC Criteria

December 18, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PR-20021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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