Effect of Paracetamol on Kidney Function in Severe Malaria

• Status: Not yet recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

Summary

A randomised open labeled, parallel-group, controlled trial to assess the efficacy of paracetamol to reduce kidney dysfunction caused by cell-free haemoglobin-mediated oxidative damage in paediatric patients with falciparum malaria complicated by intravascular haemolysis.

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

Details

• Lead Sponsor: University of British Columbia
• Collaborators: Kinshasa Medical Oxford Research Unit; Mahidol Oxford Tropical Medicine Research Unit
• Treatments: Acetaminophen

Criteria

Inclusion Criteria:

1. Male or Female, patients aged 1 to ≤ 14 years

2. Severe P. falciparum malaria, confirmed by positive blood smear with asexual forms of P. falciparum or positive PfHRP2 rapid diagnostic test (RDT).

Pre-specified modified criteria for severe falciparum malaria

Upon hospital admission, asexual parasitaemia plus at least ONE of the following:

• Glasgow coma score < 11/15 or Blantyre coma score <3/5 in pre-verbal children

• Generalized convulsions (≥2 in 24 hours)

• Jaundice (visible jaundice)

• Severe anaemia (HCT <15%/Hb<5 g/dL: aged <12) Severe anaemia (HCT <20%/Hb<7 g/dL:

aged ≥12)

• Hyperparasitaemia (>10%)

• Hypoglycaemia (glucose < 2.2 mmol/L; <40 mg/dL)

• Kidney dysfunction (blood urea > 20 mmol/L)

• Acidosis (venous bicarbonate <15 mmol/L or base excess less than -3.3mEq/L)

• Venous lactate > 5 mmol/L

• Shock (systolic blood pressure < 70 mmHg (<12 years) <80 mmHg (≥12 years) with cool extremities or capillary refill >3 seconds)

• Respiratory distress (costal indrawing, use of accessory muscles, nasal flaring, deep breathing or severe tachypnea (respiratory rate>ULN for age)

• Spontaneous bleeding

• Prostration (inability to set upright, or drink)* Abbreviations: HCT, haematocrit; Hb, haemoglobin; *cannot be only severity criteria

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

4. Less than 24 hours of antimalarial therapy

5. Attending caregiver of participant willing and able to give informed consent for participation in the study

Exclusion Criteria:

The participant may not enter the trial if ANY of the following apply:

1. Contraindication or known allergy to paracetamol

2. Known chronic liver disease or tender hepatomegaly

3. Known chronic kidney disease, history of renal replacement therapy or renal biopsy

4. Participants who are already enrolled in another research trial involving an investigational product or have participated to the same study before