The purpose of this trial is to determine if dichloroacetate (DCA) in combination with standard antimalarial drug therapy will decrease the mortality of African children infected with Plasmodium falciparum complicated by lactic acidosis. The rationale for this phase III clinical trial is based on the fact that lactic acidosis is the major clinical predictor of mortality in severely infected African children and the fact that DCA acutely lowers circulating lactate. It is therefore hypothesized that this adjunct therapy may """"""""buy time"""""""" for the patient until specific antimalarial therapy becomes effective. This trial seeks to establish: 1) if DCA administration will prolong survival time of recipients; 2) if the kinetics of DCA metabolism are important in predicting its therapeutic efficacy, 3) if DCA will ameliorate the various morbid complications of malaria and lactic acidosis; and, 4) if DCA interferes with the pharmacokinetics of quinine which is commonly used to treat malaria in African hospitals. These questions will be addressed in a masked, placebo- controlled clinical trial in which patients will be randomized to receive either intravenous DCA or placebo. Inclusion criteria for the trial will include lactate more than 5mM and parasitologic proof of severe malaria infection. Patients will be studied at the Komofo-Anokye Teaching Hospital in Kumasi, Ghana where personnel and resources exist to conduct the patient oriented aspects of the study. Core facilities exist in the U.S. (Univ Florida School of medicine, Gainesville) and U.K. (St. George's Hospital, London) to formulate, code and disperse intravenous preparations of DCA and placebo, analyze DCA and quinine in plasma, investigate autopsy specimens, and quantitate parasitemia. All relevant clinical, biochemical, pharmacologic and pathologic data will be collected and analyzed by a Biostatistics Coordinating Center (BCC). The overall progress of the trial will be monitored by two standing committees: 1) a Steering and planning Committee that includes the Study Chairmen and members of the Clinical Center, Core Laboratories and the BCC, and 2) an External Advisory Committee comprised of experts in malaria, lactic acidosis and biostatistics who, together with a representative of the lay public, will periodically review the unmasked data and oversee ethical aspects of the trial.
| Planche, Tim; Agbenyega, Tsiri; Bedu-Addo, George et al. (2003) A prospective comparison of malaria with other severe diseases in African children: prognosis and optimization of management. Clin Infect Dis 37:890-7 |
