Effect of Paracetamol on Renal Function in Plasmodium Knowlesi Malaria

• Status: Completed
• Trial end date: 2018-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Acute kidney injury is a common complication of severe Plasmodium knowlesi malaria, and an important contributor to mortality.

The exact pathogenic mechanisms of AKI in knowlesi malaria are not known, however it is hypothesised that haemolysis of red blood cells and subsequent release of cell-free haemoglobin leads to oxidative stress and lipid peroxidation in the renal tubules.

A novel mechanism of paracetamol was recently demonstrated, showing that paracetamol acts as a potent inhibitor of hemoprotein-catalyzed lipid peroxidation. In a proof of concept trial, paracetamol at therapeutic levels was shown to significantly decrease oxidative kidney injury and improve renal function by inhibiting the hemoprotein-catalyzed lipid peroxidation in a rat model of rhabdomyolysis-induced renal injury.

The investigators hypothesize that this novel inhibitory mechanism of paracetamol may provide renal protection in adults with knowlesi malaria by reducing the hemoprotein-induced lipid peroxidation that occurs in haemolytic conditions. As there is currently no consensus that exists concerning adequate medical treatment for severe malaria complicated by intravascular haemolysis and AKI, the potential application of paracetamol would be of benefit, especially as it is safe and widely available.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Menzies School of Health Research
• Treatments: Acetaminophen; Artemether; Artemether-lumefantrine combination; Artemisinins; Artesunate; Lumefantrine

Criteria

Inclusion Criteria:

1. Patient age ≥ 5 years

2. Presence of P. knowlesi malaria, confirmed by positive blood smear with asexual forms of P. knowlesi.

3. Temperature >38C on admission or fever during the preceding 48 hours

4. Enrolled within 18 hours of commencing antimalarial treatment

5. Written informed consent from patient or attending relative able to and willing to give informed consent. Consent form and information sheets will be translated into Malay and copies provided to the patient.

Exclusion Criteria:

1. Patient or relatives unable or unwilling to give informed consent

2. Contraindication or allergy to paracetamol or artesunate therapy

3. Known cirrhosis, or >6 standard alcoholic drinks/day

4. Pregnancy