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


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


METHODS
High-dependency unit, Kilifi District Hospital, Kenya.


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


METHODS
Boluses (20-40 mL/kg) of 6% Dextran 70 and 6% hydroxyethyl starch (130/0.4).


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.
KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.
Samuel O
SO
Akech
Julie
J
Jemutai
Molline
M
Timbwa
Esther
E
Kivaya
Mwanamvua
M
Boga
Greg
G
Fegan
Kathryn
K
Maitland
D000138:Acidosis / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000962:Antimalarials / Q000627:therapeutic use; D002423:Cause of Death; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003906:Developing Countries; D003911:Dextrans / Q000627:therapeutic use*; D005260:Female; D005440:Fluid Therapy / Q000379:methods*; D005500:Follow-Up Studies; D017052:Hospital Mortality / Q000639:trends*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D007630:Kenya; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D012151:Resuscitation / Q000379:methods; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D000962:Antimalarials; D003911:Dextrans; D006895:Hydroxyethyl Starch Derivatives