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Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria*

Akech, Samuel O. MBChB; Jemutai, Julie BSc; Timbwa, Molline Higher Dip; Kivaya, Esther BSN; Boga, Mwanamvua Higher Dip; Fegan, Greg PhD; Maitland, Kathryn MRCP, PhD

doi: 10.1097/CCM.0b013e3181e81165
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Objectives: A previous meta-analysis has shown a consistent survival benefit in children with severe malaria receiving human albumin solution compared to other resuscitation fluids. Human albumin solution is expensive and not readily available in Africa. We examined the safety and efficacy of the fluid resuscitation with two synthetic colloids, Dextran 70 and hydroxyethyl starch, to inform future trial design.

Design: An open-label randomized, controlled, phase II safety and efficacy trial.

Setting: High-dependency unit, Kilifi District Hospital, Kenya.

Patients: Children aged >6 months with severe falciparum malaria and acidosis (base deficit >8 mmol).

Interventions: Boluses (20–40 mL/kg) of 6% Dextran 70 and 6% hydroxyethyl starch (130/0.4).

Measurements and Main Results: Primary end point: resolution of shock over 8 hrs. Secondary end points include resolution of acidosis, in-hospital mortality, and adverse events (allergic reactions, pulmonary edema, and neurologic sequelae). A total of 79 children were enrolled: 39 received Dextran 70 and 40 received hydroxyethyl starch. No significant difference was observed in Dextran 70 and hydroxyethyl starch groups for shock resolution at 8 hrs: 23/37 (62%) and 25/39 (64%), respectively (p = .99). Acidosis resolution and respiratory distress were marginally superior in the hydroxyethyl starch group: 3/39 (8%) remained acidotic at 8 hrs versus 10/37 (27%) in the Dextran 70 arm (p = .05). There were four deaths (5%): two per arm, including three deaths in the coma subgroup (3/39, 8%). No other new adverse event was reported.

Conclusions: Correction of shock by volume expansion with either Dextran 70 or hydroxyethyl starch in children with severe malaria acidosis is safe with low mortality, including the highest risk cases admitted in coma. Both solutions present an attractive and practical option for consideration in future volume resuscitation trials in severe malaria.

From the KEMRI-Wellcome Trust Research Programme (SOA, JJ, MT, EK, MB, GF, KM), Centre for Geographic Medicine Research-Coast, Kilifi, Kenya; Department of Epidemiology & Population Health (GF), London School of Hygiene & Tropical Medicine, London, United Kingdom; Department of Paediatrics and Global Health Programme (KM), Faculty of Medicine, Imperial College, London, United Kingdom, and the Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College, London, United Kingdom.

KEMRI-Wellcome Trust Programme received a Wellcome Trust Major Overseas Award to support its core scientific activities (grant number 077092). SA is supported by grant 084538 from the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Registration: ISRCTN REGISTER, registration number 35536139. URL http://controlled-trials.com/ISRCTN35536139. Trial sponsor: Oxford University.

The authors do not have any potential conflicts of interest to disclose.

For information regarding this article, E-mail: Kmaitland@kilifi.kemri-wellcome.org

© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins