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

NCT ID: NCT04750070

Last Updated: 2025-04-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-17

Study Completion Date

2025-11-30

Brief Summary

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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

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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.

Conditions

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Shock Hypovolemic Shock, Septic Blood Transfusion Adrenaline Dopamine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Blood Transfusion and Dopamine arm

Children in this group (Treatment plan A) will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. In addition, they 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)

Group Type ACTIVE_COMPARATOR

Blood and Dopamine

Intervention Type DRUG

Children in this group will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. They will also 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)

Blood Transfusion and Adrenaline arm

Children in this group (Treatment plan B) will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. In addition, they 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)

Group Type EXPERIMENTAL

Blood and adrenaline

Intervention Type DRUG

Children in this group will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. They will also 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)

Interventions

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Blood and Dopamine

Children in this group will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. They will also 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)

Intervention Type DRUG

Blood and adrenaline

Children in this group will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. They will also 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)

Intervention Type DRUG

Other Intervention Names

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Dopamine Blood Epinephrine Blood

Eligibility Criteria

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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
Minimum Eligible Age

1 Month

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of British Columbia

OTHER

Sponsor Role collaborator

Muhimbili University of Health and Allied Sciences

OTHER

Sponsor Role collaborator

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tahmeed Ahmed, PhD

Role: PRINCIPAL_INVESTIGATOR

International Centre for Diarrhoeal Disease Research, Bangladesh

Locations

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Icddr,B

Dhaka, , Bangladesh

Site Status RECRUITING

Countries

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Bangladesh

Central Contacts

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Monira Sarmin, MBBS, MCPS

Role: CONTACT

+8801718596947 ext. 2186

Facility Contacts

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Monira Sarmin, MCPS

Role: primary

References

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Other Identifiers

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PR-20021

Identifier Type: -

Identifier Source: org_study_id

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