Title
Safety and Efficacy of Primaquine for P. Vivax
Evaluation of Safety and Efficacy of Two Primaquine Dosing Regimens for the Radical Treatment of Plasmodium Vivax Malaria in Vanuatu and Solomon Islands
Phase
N/ALead Sponsor
Menzies School of Health ResearchStudy Type
InterventionalStatus
Unknown statusIndication/Condition
MalariaIntervention/Treatment
primaquine ...Study Participants
180The Melanesian states of the Western Pacific (Papua New Guinea, Solomon Islands and Vanuatu) represent a unique and especially prescient challenge to malaria control and elimination.
While the use of bed nets and other vector control and case management measures have achieved major advances in overall malaria control, the P. vivax and P. ovale species account for an ever-increasing burden of clinical disease.
The lack of effective treatment of the hypnozoite stages of infection with these species result in ongoing relapses and a continuing reservoir of infection.
The only known drug effective for treatment of the hypnozoite stage is primaquine; however the safe and effective dose of this drug in malaria treatment is still unclear.
A recent study evaluated the safety and efficacy of two primaquine dosing regimens (0.25mg/kg and 0.5mg/kg) in a population in New Ireland province, PNG. This study aims to replicate this methodology in Vanuatu and Solomon Islands, to provide a more complete picture of primaquine efficacy and safety in each of the three countries of this region.
Study Aims
Primary To define and compare the efficacy of standard (0.25mg/kg/day for 14 days) and high-dose (0.5mg/kg/day for 14 days) primaquine in preventing early relapses from P. vivax in Solomon Islands and Vanuatu.
Secondary To measure safety and toxicity of primaquine when administered as a standard or high-dose regimen in Melanesian adults and children in Solomon Islands and Vanuatu.
Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, and will be administered the standard recommended primaquine dose of 0.25mg/kg for 14 consecutive days.
Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, and will be administered a primaquine dose of 0.5mg/kg/day for 14 consecutive days.
Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, but will not receive primaquine until the time of confirmed recurrent parasitaemia or completion of 3 months follow up.
Inclusion Criteria: Age 12 months to 60 years Melanesian background and living in local area Microscopically (based on field microscopy) or RDT confirmed P.vivax regardless of parasite density. Mixed infections (P.falciparum-P.vivax and P.malariae-P.vivax) can be included. Exclusion Criteria: Any signs of severe malaria (see WHO definitions) including: impaired consciousness, respiratory distress, severe anaemia (Hb<5), multiple seizures, frequent vomiting/ inability to swallow tablets, prostration, jaundice, hypotension, abnormal bleeding or hypoglycaemia. Clinical evidence of non-malarial illness (such as pneumonia or otitis media) Severe malnutrition (weight-for-age nutritional Z score [WAZ] <60th percentile) Permanent disability, which prevents or impedes study participation. Treatment with primaquine in the previous 14 days Residence or planned travel outside the study area during the follow-up period (precluding supervised treatment and follow-up procedures) Known or suspected pregnancy Currently breastfeeding A positive rapid test for G6PD deficiency (Binax or Carestart RDT) Following later PCR-based confirmation of malaria speciation, there may be some post-hoc exclusion of subjects in whom it is thought the initial field-based microscopic diagnosis may have been incorrect.
