Effect of Paracetamol on Renal Function in Plasmodium Knowlesi Malaria

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.

Conditions

• Malaria

Interventions

DRUG

Paracetamol

\>50kg: Paracetamol 1gm PO/NG 6 hourly for 72 hours (maximum dose 4g/24h) plus IV artesunate or oral artemether/lumefantrine. \<50kg: Paracetamol 12.5-15mg/kg/dose 6 hourly for 72 hours (maximum total dose 5doses/24hours;75mg/kg) plus IV artesunate or oral artemether/lumefantrine.

Sponsors & Collaborators

• Menzies School of Health Research

  lead OTHER

Principal Investigators

• Giri M Rajahram, MD · Clinical Research Center, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

• Bridget Barber, MBBS · Menzies School of Health Research

• Nicholas Anstey, PhD · Menzies School of Health Research

• Matthew Grigg, MBBS · Menzies School of Health Research

• Timothy William, MBBS · Jesselton Medical Centre

• Jayaram Menon, MBBS · Ministry of Health, Malaysia

• Tsin Yeo, MBBS · Menzies School of Health Research

• Katherine Plewes, MD · Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand

• Arjen Dondorp, MD · Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand

• Daniel Cooper, MBChB · Menzies School of Health Research

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

5 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-10-31

Primary Completion

2018-02-01

Completion

2018-02-01

Countries

• Malaysia

Study Locations