OBJECTIVESA 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.DESIGNAn open-label randomized, controlled, phase II safety and efficacy trial.SETTINGHigh-dependency unit, Kilifi District Hospital, Kenya.PATIENTSChildren aged >6 months with severe falciparum malaria and acidosis (base deficit >8 mmol).INTERVENTIONSBoluses (20-40 mL/kg) of 6% Dextran 70 and 6% hydroxyethyl starch (130/0.4).MEASUREMENTS AND MAIN RESULTSPrimary 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.CONCLUSIONSCorrection 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.