Safety and Efficacy of Primaquine for P. Vivax

Menzies School of Health Research

Status: Unknown

Conditions: Malaria

Treatments: Drug: Primaquine; Drug: delayed primaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT01837992

VanSI_2013

Details and patient eligibility

About

The 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.

Full description

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.

Enrollment: 180 estimated patients

Sex: All

Ages: 12 months to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 12 months to 60 years
2. Melanesian background and living in local area
3. 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

1. 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.
2. Clinical evidence of non-malarial illness (such as pneumonia or otitis media)
3. Severe malnutrition (weight-for-age nutritional Z score [WAZ] <60th percentile)
4. Permanent disability, which prevents or impedes study participation.
5. Treatment with primaquine in the previous 14 days
6. Residence or planned travel outside the study area during the follow-up period (precluding supervised treatment and follow-up procedures)
7. Known or suspected pregnancy
8. Currently breastfeeding
9. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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180 participants in 3 patient groups

Standard dose

Active Comparator group

Description:

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.

Treatment:

Drug: Primaquine

High dose

Active Comparator group

Description:

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.

Treatment:

Drug: Primaquine

Control

Other group

Description:

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.

Treatment:

Drug: delayed primaquine