Primaquine's Gametocytocidal Efficacy in Malaria Asymptomatic Carriers (PRINOGAM)

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 3

Conditions: Malaria

Treatments: Drug: PQ (0.75); Drug: PQ (0.4); Drug: PQ (0.2); Drug: DHA-PPQ

Study type: Interventional

Funder types: Other

Identifiers

NCT01838902

SCC 1321

Details and patient eligibility

About

In this study, the investigators are interested to know if lower doses of Primaquine together with dihydroartemisinin-piperaquine can produce a similar effect of clearing both sexual and asexual parasites in asymptomatic carriers compared to the recommended dose of primaquine but with a decreased risk of haemolysis.

Children (> 1 year) and adults with normal Glucose-6-phosphate dehydrogenase enzyme levels but with asexual Plasmodium falciparum parasites on the day of screening will be invited to take part in this study.

Full description

To date, primaquine (PQ), an 8-aminoquinoline, is the only currently registered product able to clear P. falciparum mature gametocytes. However, its use has been and is still limited by its haematological toxicity (haemolytic anaemia), particularly but not exclusively in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd), in whom haemolysis can occur after a single PQ dose. Such an effect is dose-dependent. Considering that the current recommended dose was established several decades ago on a small number of experimentally challenged volunteers, it may be possible to obtain the same effect with a lower dose and hence decrease the risk of haemolysis. The proposed study is a four-arm, open label, randomized, controlled trial. G6PD-normal asymptomatic P. falciparum infected individuals identified through population screening will be randomized to receive either a complete course of dihydroartemisinin-piperaquine (DHA-PPQ) alone (control arm) or a complete course of DHA-PPQ plus a single dose of PQ at 3 differing dose strengths (intervention arms), i.e. 0.75mg/kg, 0.4mg base/kg and 0.2mg base/kg.

The study is planned to enroll 1,200 individuals with an asymptomatic malaria infection during the rainy /transmission season (June - December) from villages around the MRC's field stations at Walikunda and Basse in The Gambia. Asymptomatic parasite carriers identified by qualitative (RDT) and quantitative (parasites counts >20/µl by slide microscopy) methods during population screening exercises at the villages will be invited for a written informed consent and further screening to confirm eligibility, including tests for qualitative G6PD enzyme function (fluorescence spot test) and haemoglobin. If eligible, they will be assigned to one of four study arms using a block randomization scheme in a 1:1:1:1 ratio ensuring a balance in enrollment between the four groups. Enrolled participants will receive ACT treatment on days 0, 1 and 2. On day 2, participants allocated to the PQ arms will receive a dose of primaquine based on determined body weight.

Each participant involvement consists of a maximum of 11 visits over a 42 day period after initiation of treatment. The primary end point is the prevalence of P. falciparum gametocyte carriers at day 7, as determined by QT-NASBA.

Enrollment: 467 patients

Sex: All

Ages: 12+ months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Age ≥1 year

• Weight >10 Kg
• P. falciparum mono-infection, density of at least 20 parasites/μL
• Axillary temperature < 37.5ºC
• Resident in the study area and willingness to reside for the duration of the study
• Written informed consent (plus an assent in children >12years of age)

Exclusion criteria

• G6PD Deficiency Haemoglobin <8g/dl

  • Known allergy to any of the study medications
  • Known Pregnancy or breastfeeding
  • Clear/documented history of anti-malarial treatment 2 weeks before contact with study team
  • History of blood transfusion in the previous 3 months
  • Any chronic or acute conditions that might interfere with the study as judged by the research clinician
  • History of sickle cell anaemia

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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467 participants in 4 patient groups

Eurartesim (control)

Other group

Description:

All participants will receive a complete course of DHA-PPQ (Eurartesim)

Treatment:

Drug: DHA-PPQ

Primaquine 0.75mg base/kg

Experimental group

Description:

Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.75mg/kg body weight

Treatment:

Drug: DHA-PPQ

Drug: PQ (0.75)

Primaquine 0.4mg base /kg

Experimental group

Description:

Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.4mg base/kg Body weight

Treatment:

Drug: DHA-PPQ

Drug: PQ (0.4)

Primaquine 0.2mg base/kg

Experimental group

Description:

Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.2mg base/kg body weight

Treatment:

Drug: DHA-PPQ

Drug: PQ (0.2)