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| Name | Class |
|---|---|
| University of British Columbia | OTHER |
| Muhimbili University of Health and Allied Sciences | OTHER |
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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.
Background:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Blood Transfusion and Dopamine arm | Active Comparator | 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) |
|
| Blood Transfusion and Adrenaline arm | Experimental | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood and Dopamine | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Case fatality rate | Number of mortalities among acutely malnourished children presenting with diarrhea and fluid refractory shock who would receive WHO standard fluid therapy followed by blood transfusion with either dopamine or adrenaline. | 28 days (± 3 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment failure rates | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Monira Sarmin, MBBS, MCPS | Contact | +8801718596947 | 2186 | drmonira@icddrb.org |
| Name | Affiliation | Role |
|---|---|---|
| Tahmeed Ahmed, PhD | International Centre for Diarrhoeal Disease Research, Bangladesh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icddr,B | Recruiting | Dhaka | 1000 | Bangladesh |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24006557 | Background | Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Childhood Illnesses. 2nd edition. Geneva: World Health Organization; 2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK154447/ | |
| Background | AABB. Technical Manual. 19th ed. Fung MK, Eder AF, Spitalnik SL, Westhoff CM, editors. United States. | ||
| Background | Green REB, Klostermann DA. The Antiglobulin Test. In: Harmening D, editor. Modern Blood Banking & Transfusion Practices. 6th ed. Philadelphia: F.A. Davis. p. 107-10. | ||
| 21627690 |
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| ID | Term |
|---|---|
| D012769 | Shock |
| D012772 | Shock, Septic |
| D000067011 | Severe Acute Malnutrition |
| D002771 | Cholera |
| D013851 | Thinness |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018805 | Sepsis |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D004298 | Dopamine |
| D004837 | Epinephrine |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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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
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|
|
| Blood and adrenaline | 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) |
|
|
Number of children who would require mechanical ventilation
| Through study completion, an average of 7 days |
| Heart failure | 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 a child stays in ICU | Through study completion, an average of 7 days |
| Time-to-achieve recovery | Required times (minutes) for resuscitation of a child after randomization to a specific arms | 3-4 hours |
| Left ventricular function of the study participants | 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 | 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 | 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 a child stays in the hospital | variable (days to months) |
| Mean arterial pressure (MAP) stabilization at 48 hours | Number of children whose MAP was stabilized at 48 hours | 48 hours from the point of inclusion in the study |
| Result |
| Chisti MJ, Pietroni MA, Smith JH, Bardhan PK, Salam MA. Predictors of death in under-five children with diarrhoea admitted to a critical care ward in an urban hospital in Bangladesh. Acta Paediatr. 2011 Dec;100(12):e275-9. doi: 10.1111/j.1651-2227.2011.02368.x. Epub 2011 Jun 21. |
| 24661049 | Result | Sarmin M, Ahmed T, Bardhan PK, Chisti MJ. Specialist hospital study shows that septic shock and drowsiness predict mortality in children under five with diarrhoea. Acta Paediatr. 2014 Jul;103(7):e306-11. doi: 10.1111/apa.12640. Epub 2014 Apr 11. |
| 10371570 | Result | Ahmed T, Ali M, Ullah MM, Choudhury IA, Haque ME, Salam MA, Rabbani GH, Suskind RM, Fuchs GJ. Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol. Lancet. 1999 Jun 5;353(9168):1919-22. doi: 10.1016/S0140-6736(98)07499-6. |
| 26440279 | Result | Chisti MJ, Salam MA, Bardhan PK, Faruque AS, Shahid AS, Shahunja KM, Das SK, Hossain MI, Ahmed T. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study. PLoS One. 2015 Oct 6;10(10):e0139966. doi: 10.1371/journal.pone.0139966. eCollection 2015. |
| 29318195 | Result | Sarker AR, Sultana M, Mahumud RA, Ali N, Huda TM, Salim Uzzaman M, Haider S, Rahman H, Islam Z, Khan JAM, Van Der Meer R, Morton A. Economic costs of hospitalized diarrheal disease in Bangladesh: a societal perspective. Glob Health Res Policy. 2018 Jan 5;3:1. doi: 10.1186/s41256-017-0056-5. eCollection 2018. |
| 1632474 | Result | Guerrant RL, Schorling JB, McAuliffe JF, de Souza MA. Diarrhea as a cause and an effect of malnutrition: diarrhea prevents catch-up growth and malnutrition increases diarrhea frequency and duration. Am J Trop Med Hyg. 1992 Jul;47(1 Pt 2):28-35. doi: 10.4269/ajtmh.1992.47.28. |
| 19593244 | Result | Chisti MJ, Saha S, Roy CN, Salam MA. Predictors of bacteremia in infants with diarrhea and systemic inflammatory response syndrome attending an urban diarrheal treatment center in a developing country. Pediatr Crit Care Med. 2010 Jan;11(1):92-7. doi: 10.1097/PCC.0b013e3181b063e1. |
| 24196006 | Result | Ranjit S, Aram G, Kissoon N, Ali MK, Natraj R, Shresti S, Jayakumar I, Gandhi D. Multimodal monitoring for hemodynamic categorization and management of pediatric septic shock: a pilot observational study*. Pediatr Crit Care Med. 2014 Jan;15(1):e17-26. doi: 10.1097/PCC.0b013e3182a5589c. |
| 28509730 | Result | Davis AL, Carcillo JA, Aneja RK, Deymann AJ, Lin JC, Nguyen TC, Okhuysen-Cawley RS, Relvas MS, Rozenfeld RA, Skippen PW, Stojadinovic BJ, Williams EA, Yeh TS, Balamuth F, Brierley J, de Caen AR, Cheifetz IM, Choong K, Conway E Jr, Cornell T, Doctor A, Dugas MA, Feldman JD, Fitzgerald JC, Flori HR, Fortenberry JD, Graciano AL, Greenwald BM, Hall MW, Han YY, Hernan LJ, Irazuzta JE, Iselin E, van der Jagt EW, Jeffries HE, Kache S, Katyal C, Kissoon N, Kon AA, Kutko MC, MacLaren G, Maul T, Mehta R, Odetola F, Parbuoni K, Paul R, Peters MJ, Ranjit S, Reuter-Rice KE, Schnitzler EJ, Scott HF, Torres A Jr, Weingarten-Arams J, Weiss SL, Zimmerman JJ, Zuckerberg AL. American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock. Crit Care Med. 2017 Jun;45(6):1061-1093. doi: 10.1097/CCM.0000000000002425. |
| 21615299 | Result | Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM; FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011 Jun 30;364(26):2483-95. doi: 10.1056/NEJMoa1101549. Epub 2011 May 26. |
| 9842034 | Result | Seri I, Abbasi S, Wood DC, Gerdes JS. Regional hemodynamic effects of dopamine in the sick preterm neonate. J Pediatr. 1998 Dec;133(6):728-34. doi: 10.1016/s0022-3476(98)70141-6. |
| 23496872 | Result | Maitland K, George EC, Evans JA, Kiguli S, Olupot-Olupot P, Akech SO, Opoka RO, Engoru C, Nyeko R, Mtove G, Reyburn H, Brent B, Nteziyaremye J, Mpoya A, Prevatt N, Dambisya CM, Semakula D, Ddungu A, Okuuny V, Wokulira R, Timbwa M, Otii B, Levin M, Crawley J, Babiker AG, Gibb DM; FEAST trial group. Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Med. 2013 Mar 14;11:68. doi: 10.1186/1741-7015-11-68. |
| 8194289 | Result | Phornphatkul C, Pongprot Y, Suskind R, George V, Fuchs G. Cardiac function in malnourished children. Clin Pediatr (Phila). 1994 Mar;33(3):147-54. doi: 10.1177/000992289403300304. |
| 26323041 | Result | Ventura AM, Shieh HH, Bousso A, Goes PF, de Cassia F O Fernandes I, de Souza DC, Paulo RL, Chagas F, Gilio AE. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med. 2015 Nov;43(11):2292-302. doi: 10.1097/CCM.0000000000001260. |
| 27673385 | Result | Ramaswamy KN, Singhi S, Jayashree M, Bansal A, Nallasamy K. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med. 2016 Nov;17(11):e502-e512. doi: 10.1097/PCC.0000000000000954. |
| 32032273 | Result | Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, Nadel S, Schlapbach LJ, Tasker RC, Argent AC, Brierley J, Carcillo J, Carrol ED, Carroll CL, Cheifetz IM, Choong K, Cies JJ, Cruz AT, De Luca D, Deep A, Faust SN, De Oliveira CF, Hall MW, Ishimine P, Javouhey E, Joosten KFM, Joshi P, Karam O, Kneyber MCJ, Lemson J, MacLaren G, Mehta NM, Moller MH, Newth CJL, Nguyen TC, Nishisaki A, Nunnally ME, Parker MM, Paul RM, Randolph AG, Ranjit S, Romer LH, Scott HF, Tume LN, Verger JT, Williams EA, Wolf J, Wong HR, Zimmerman JJ, Kissoon N, Tissieres P. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med. 2020 Feb;21(2):e52-e106. doi: 10.1097/PCC.0000000000002198. |
| 30065491 | Result | Sun JT. New Advances in Emergency Ultrasound Protocols for Shock. J Med Ultrasound. 2017 Oct-Dec;25(4):191-194. doi: 10.1016/j.jmu.2017.09.005. Epub 2017 Dec 6. No abstract available. |
| 28144779 | Result | Sekiguchi H, Harada Y, Villarraga HR, Mankad SV, Gajic O. Focused cardiac ultrasound in the early resuscitation of severe sepsis and septic shock: a prospective pilot study. J Anesth. 2017 Aug;31(4):487-493. doi: 10.1007/s00540-017-2312-8. Epub 2017 Jan 31. |
| 31821418 | Result | McQuilten ZK, Cooper DJ. Age of Red Blood Cells for Transfusion in Critically Ill Pediatric Patients. JAMA. 2019 Dec 10;322(22):2175-2176. doi: 10.1001/jama.2019.17476. No abstract available. |
| 28316439 | Result | Tiwari AK, Aggarwal G, Dara RC, Arora D, Gupta GK, Raina V. First Indian study to establish safety of immediate-spin crossmatch for red blood cell transfusion in antibody screen-negative recipients. Asian J Transfus Sci. 2017 Jan-Jun;11(1):40-44. doi: 10.4103/0973-6247.200774. |
| 37045565 | Derived | Sarmin M, Shaly NJ, Sultana T, Tariqujjaman M, Shikha SS, Mariam N, Jeorge DH, Tabassum M, Nahar B, Afroze F, Shahrin L, Hossain MI, Alam B, Faruque ASG, Islam MM, Osmany DMF, Ahmed CM, Manji K, Kissoon N, Chisti MJ, Ahmed T. Efficacy of dopamine, epinephrine and blood transfusion for treatment of fluid refractory shock in children with severe acute malnutrition or severe underweight and cholera or other dehydrating diarrhoeas: protocol for a randomised controlled clinical trial. BMJ Open. 2023 Apr 12;13(4):e068660. doi: 10.1136/bmjopen-2022-068660. |
| D018746 |
| Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D014735 | Vibrio Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |