Clinical trial NCT04750070: Management of Shock in Children With SAM or Severe Underweight and Diarrhea
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Shock Hypovolemic
Shock, Septic
Blood Transfusion
Adrenaline
Dopamine
Keywords: Severe acute malnutrition
Children
Shock
Cholera
Dehydrating diarrhea
Severe underweight
Acute malnutrition
Lead sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
Sponsor class: OTHER
Collaborators: name: University of British Columbia
name: Muhimbili University of Health and Allied Sciences
First posted: 2021-02-11
Enrollment: 135
Sex: ALL
Minimum age (years): 1
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Systematic evaluation of the effects of blood transfusion and inotrope(s) and vasopressor in children with dehydrating diarrhea (for example, in cholera) and acute malnutrition having fluid refractory shock and unresponsive to WHO standard fluid therapy
Primary purpose: TREATMENT

Brief summary: 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.

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 blood transfusion and adrenaline compared to blood transfusion and dopamine, 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 blood transfusion with either dopamine or adrenaline.

Methods: This will be a randomized, two-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 blood transfusion and dopamine versus blood transfusion and adrenaline. Children in both groups will also receive inj hydrocortisone. After parental written informed consent, children, in addition to usual supportive care, will be allocated to the study interventions following randomization.

Eligibility criteria: Inclusion Criteria:

1. Children of either sex with acute malnutrition and diarrhea
2. Age: 1-59 months
3. Children with cerebral palsy (CP) and/or developmental delay, Down Syndrome with or without heart diseases
4. Fluid refractory shock
5. Consent from the caregivers/parents

Exclusion Criteria:

1. Having a rare blood group (Rh negative blood groups provided that donor is not available)
2. A child requiring cardio-pulmonary resuscitation during screening or having gasping respiration

Primary outcomes:
measure: Case fatality rate
timeFrame: 28 days (± 3 days)
Secondary outcomes:
measure: Treatment failure rates
timeFrame: Through study completion, an average of 7 days
measure: Need for mechanical ventilation
timeFrame: Through study completion, an average of 7 days
measure: Heart failure
timeFrame: Through study completion, an average of 7 days
measure: Length of ICU stay
timeFrame: Through study completion, an average of 7 days
measure: Time-to-achieve recovery
timeFrame: 3-4 hours
measure: Left ventricular function of the study participants
timeFrame: Through study completion, an average of 7 days
measure: Right ventricular function of the study participants
timeFrame: Through study completion, an average of 7 days
measure: Inferior vena cava collapsibility of the study participants
timeFrame: Through study completion, an average of 7 days
measure: Length of hospital stay
timeFrame: variable (days to months)
measure: Mean arterial pressure (MAP) stabilization at 48 hours
timeFrame: 48 hours from the point of inclusion in the study
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Icddr,B
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Tahmeed Ahmed, PhD
role: PRINCIPAL_INVESTIGATOR
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