Paracetamol Effect on Oxidative Stress and Renal Function in Severe Malaria

Overview:

Blackwater fever, characterized by intravascular haemolysis and haemoglobinuria, is an important cause of renal impairment and mortality in severe malaria caused by Plasmodium falciparum.

In a recent proof of concept trial, paracetamol at therapeutic levels was shown to significantly decrease oxidant kidney injury, improve renal function and reduce renal damage by inhibiting the haemoprotein-catalyzed lipid peroxidation in a rat model of rhabdomyolysis-induced renal injury. The investigators hypothesize that paracetamol may provide renal protection in severe malaria patients by reducing the haemoprotein-induced lipid peroxidation. As there is currently no consensus that exists concerning adequate medical treatment for blackwater fever, the potential application of this well tolerated and extensively used drug would be of great benefit.

This study measures primarily:

  • The effect of paracetamol concentrations on renal function, peak creatinine levels or trough creatinine clearance in patients with severe and moderately severe falciparum malaria stratified by the level of intravascular haemolysis

Secondarily:

  • The duration of Acute Kidney Injury (AKI) and development of AKI between the treatment and control arm
  • Correlations between oxidative stress, cell-free haemoglobin and renal function
  • Assessment of Blackwater fever and association with renal function
  • Mortality and haemodialysis trends
  • Host factors of Intravascular Haemolysis
  • Fever clearance time
  • Parasite clearance time
  • Parasite sequestration
  • Assessment of Acute Kidney Injury
  • Urine scoring of dehydration and haemolysis
  • Safety assessment
  • Assess the antimalarial drug sensitivity of patients treated with paracetamol
  • Paracetamol pharmacokinetics and pharmacodynamics
  • Area under the plasma concentration versus time curve (AUC)
  • The maximum concentration (Cmax)