Safety and Tolerability of Low Dose Primaquine

Malaria Consortium

Status and phase: Completed; Phase 4

Conditions: Malaria, Falciparum; G6PD Deficiency

Treatments: Drug: Dihydroartemisinin piperaquine (DHA PP); Drug: Primaquine

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02434952

015NECHR

Details and patient eligibility

About

In Cambodia, falciparum is becoming more difficult to treat because drugs are becoming less effective. The investigators can help to try to prevent the spread of this resistant malaria by adding a drug that will make it more difficult for the mosquito to drink up the malaria in people's blood. If the mosquito cannot drink up the malaria, then the malaria cannot develop in the mosquito so it will not be able to inject malaria back into people when it bites. The drug the investigators will use is called primaquine.

Primaquine commonly causes the red cells in the blood to break apart if they are weak. Red cells need enzymes to work properly and weak red cells have low amounts of an enzyme called glucose 6 phosphate dehydrogenase (G6PD). The investigators want to know if treating malaria with primaquine will be safe for the red cells. To do this study, the investigators need to know if a subject has low G6PD or not.

Enrollment: 109 patients

Sex: All

Ages: 1+ year old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 1 year
• Presentation with a confirmed fever (≥ 38⁰C axilla or ≥ 37.5⁰C aural) or history of fever in previous 48 hours +/- other clinical features of uncomplicated malaria
• Plasmodium falciparum monoinfection ≥ 1 asexual form / 500 white blood cells
• Informed consent (written/verbal) provided by patient or relative/legal guardian
• Signed Assent form for children aged 12 to < 18 years

Exclusion criteria

• Clinical signs of severe malaria or danger signs
• Pregnant or breast feeding
• Unable or unwilling to take a pregnancy test (for women of child-bearing age)
• Women intending to become pregnant in the next 3 months
• Allergic to primaquine or DHA PP
• Patients taking drugs known to cause acute intravascular haemolytic anaemia (AIHA) in G6PD deficiency e.g. dapsone, nalidixic acid
• Patients on treatment for a significant illness e.g. HIV, tuberculosis (TB) treatment, steroids
• On drugs that could interfere with anti-malarial pharmacokinetics like antiretrovirals, cimetidine, ketoconazole, antiepileptic drugs, rifampicin

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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109 participants in 4 patient groups

DHA PP plus primaquine, G6PD deficiency

Experimental group

Description:

Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (\<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP. Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children \<18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (\<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.

Treatment:

Drug: Primaquine

Drug: Dihydroartemisinin piperaquine (DHA PP)

DHA PP plus primaquine, G6PD normal

Active Comparator group

Description:

Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (\<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP. Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children \<18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (\<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.

Treatment:

Drug: Primaquine

Drug: Dihydroartemisinin piperaquine (DHA PP)

DHA PP alone, G6PD deficiency

Active Comparator group

Description:

Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (\<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.

Treatment:

Drug: Dihydroartemisinin piperaquine (DHA PP)

DHA PP alone, G6PD normal

Active Comparator group

Description:

Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (\<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.

Treatment:

Drug: Dihydroartemisinin piperaquine (DHA PP)