Parenteral Artesunate Compared to Quinine as a Cause of Late Anaemia in African Children With Malaria (DHART)

University of Oxford

Status and phase: Completed; Phase 4

Conditions: Anaemia

Treatments: Drug: artesunate; Drug: quinine

Study type: Interventional

Funder types: Other

Identifiers

NCT02092766

KIMORU005

Details and patient eligibility

About

Delayed anaemia has been reported in European travellers with malaria cured by artesunate. Although no deaths related to this delayed anaemia have been reported so far, blood transfusion has been necessary in some affected patients. Recent observations suggest that this episodes of anaemia also occurs in endemic countries. The aim of this trial is to assess the incidence of late onset anaemia after treatment with intravenous artesunate compared to intravenous quinine, to identify patients at risk and to clarify the causes of this delayed anaemia.

Enrollment: 217 patients

Sex: All

Ages: 6 months to 14 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age > 6 months and ≤ 14 years
• Acute uncomplicated P. falciparum malaria, confirmed by positive blood smear with asexual forms of P. falciparum or mixed with non-falciparum species
• Asexual P. falciparum parasitaemia ≥ 100,000/uL and ≤500,000/uL
• Haemoglobin ≥5.0 g/dL
• Parents/guardians agree to hospitalize the child for the length of treatment (3 days) and bring the patient for planned follow-up visits at day 7, 14, 21, 28, 35, 42
• Signed consent from the guardian/parents

Exclusion criteria

• Body weight ≤ 5 kg
• Severe malaria or signs of severe malaria as defined by WHO Guidelines 2013
• History of hypersensitivity or contraindication to quinine or artesunate
• A clear history of adequate antimalarial treatment in the preceding 24 hours with drugs expected to be effective
• Presence of intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the patient treatment or results of the study
• Participation in another clinical trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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217 participants in 2 patient groups

IV artesunate

Experimental group

Description:

Intravenous artesunate 2.4 mg/kg body weight STAT, then 2.4 mg/kg at 12, 24, 48 and 72 hours (5 doses total)

Treatment:

Drug: artesunate

IV quinine

Active Comparator group

Description:

Intravenous quinine dihydrochloride 20 mg salt/kg body weight loading dose over 4 hours, then 10 mg/kg over 2 hours 8 hourly until 72 hours (9 doses total)

Treatment:

Drug: quinine