Falciparum Malaria, Malaria, Vivax Malaria
Conditions
Brief summary
This study is designed as a multi-centre randomized, open label trial to compare the safety and efficacy of a high dose primaquine (PQ) treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.
Detailed description
Plasmodium vivax forms dormant liver stages that reactivate weeks or months following an acute infection. Recurrent infections can be associated with a febrile illness, a cumulative risk of severe anaemia, direct and indirect mortality, and are the most important source of onward transmission of the parasite. In co-endemic areas, there is a very high risk (up to 50%) of patients representing with P. vivax malaria following treatment of P. falciparum. Hence, in co-endemic regions there is a strong rationale for eradicating P. vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infections. The recently completed multicentre IMPROV study compared the efficacy of a 7 day primaquine regimen (1.0 mg/kg/day for 7 days) with a 14 day regimen (0.5 mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5-fold more efficacious at reducing P. vivax recurrence than the control. This study is designed as a multicentre randomized, open label trial to compare the safety and efficacy of a high dose PQ treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.
Interventions
DRUGprimaquine
Primaquine regimen over 7 days (1.0 mg/kg/day for 7 days)
Sponsors
International Centre for Diarrhoeal Disease Research, Bangladesh
Tribhuvan University, Nepal
Arba Minch University
Addis Ababa University
Menzies School of Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* P. falciparum mono-infection * Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours * Age \>1 years (≥ 18 years at the Ethiopia site) * G6PD normal as defined by the Biosensor (SD Biosensor, ROK) at ≥70% of the adjusted male median (AMM) for each site * Written informed consent * Able to comply with all study procedures and timelines
Exclusion criteria
* General danger signs or symptoms of severe malaria * Anaemia, defined as Hb \<8g/dl * Pregnant women as determined by Urine β-HCG pregnancy test * Breast feeding women * Known hypersensitivity to any of the drugs given * Regular use of drugs with haemolytic potential * Blood transfusion within the last 4 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence risk of any P. vivax parasitaemia at day 63 | 63 days | The incidence risk of any P. vivax parasitaemia at day 63 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence risk of all any P. vivax parasitaemia at day 28 and 42 | 28 and 42 days | Incidence risk of all any P. vivax parasitaemia at day 28 and 42 |
| Incidence risk of any P. falciparum malaria at day 28, 42 and 63 | 28/42/63 days | incidence risk of any P. falciparum malaria at day 28, 42 and 63 |
| proportion of patients vomiting their medication within 1 hour of administration | 1 hour | proportion of patients vomiting their medication on the day of enrollment within 1 hour of administration |
| proportion of patients vomiting any of their PQ doses within 1 hour of administration | 7 days | proportion of patients vomiting any of their PQ doses within 1 hour of administration |
| proportion of adverse events and serious adverse events | 63 days | proportion of adverse events and serious adverse events |
| Incidence risk of symptomatic P. vivax parasitaemia at day 63 | 63 days | incidence risk of symptomatic P. vivax parasitaemia at day 63 |
| • The incidence risk of ≥25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7 | 7 days | • The incidence risk of ≥25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7 |
| The incidence risk of ≥25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7 | day 7 | The incidence risk of ≥25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7 |
| Incidence risk of P. falciparum gametocytaemia between day 7 and 63 | 63 days | Incidence risk of P. falciparum gametocytaemia between day 7 and 63 |
| Parasite clearance on day 1, 2 and 3 | 3 days | Parasite clearance on day 1, 2 and 3 |
| Fever clearance on day 1, 2 and 3 | 3 days | Fever clearance on day 1, 2 and 3 |
| incidence risk of severe anaemia (Hb<5g/dl) and moderately severe anaemia (<7g/dl) and/or the risk for blood transfusion between day 3 and 7 | 7 days | incidence risk of severe anaemia (Hb\<5g/dl) and moderately severe anaemia (\<7g/dl) and/or the risk for blood transfusion between day 3 and 7 |
Countries
Bangladesh, Ethiopia, Indonesia
Outcome results
None listed