Safety and Efficacy of Primaquine for P. Vivax

Menzies School of Health Research180 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

180

Conditions

Malaria

Eligibility

Sex: ALLMin age: 12 MonthsMax age: 60 Years

Medical Language ↔ Plain English

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.

Locations (4)

Tetere Hospital, Guadalcanal Province

Honiara, Guadalcanal Province, Solomon Islands

Aoki Hospital, Malaita Province

Auki, Malaita Province, Solomon Islands

Northern Provincial Hospital, Nambauk Aid Post, V.F.H.A Dispensary and Fanafo Dispensary

Luganville, Sanma, Vanuatu

Toroa Dispensary, NTM Health Centre and Vila Central Hospital

Port Vila, Shefa Province, Vanuatu

Outcomes

Primary Outcomes

Efficacy: Numbers of Plasmodium vivax relapses per person-years of follow-

Total number of microscopically diagnosed (including both symptomatic and asymptomatic infections), PCR-confirmed relapses with Plasmodium vivax in participants in each treatment arm over the 3-month follow-up period, expressed as number of relapses per person-years of follow-up.

Time frame: 12 months

Secondary Outcomes

Safety and toxicity (1): Numbers with mild adverse events

Numbers in each treatment arm experiencing any documented adverse event defined as "mild" (not severe enough to interfere with daily activities).

Time frame: 12 months

Safety and toxicity (2) Numbers with moderate adverse events

Numbers in each treatment arm experiencing any documented adverse event defined as "moderate" (severe enough to interfere with daily activities but not severe enough to warrant admission to hospital).

Time frame: 12 months

Safety and toxicity (3) Numbers with severe adverse events

Numbers in each treatment arm experiencing any documented adverse event defined as "severe" (severe to warrant admission to hospital or to be considered a risk for death or disability arising from the event).

Time frame: 12 months

Safety and toxicity (4) Numbers with any adverse events

Numbers in each treatment arm experiencing any documented event (defined as either mild, moderate or severe as above).

Time frame: 12 months

Safety and toxicity (5) Numbers with assumed significant haemolysis

Numbers in each treatment arm experiencing any of the following: 1. Haemoglobinuria on dipstick examination 2. Scleral icterus 3. Haemoglobin concentration fall by more than 25% of baseline or absolute concentration \<5g/dL

Time frame: 12 months

Safety and toxicity (6) Numbers with significant methaemoglobinaemia

Numbers in each treatment arm experiencing any of the following: 1. Cyanosis (blue tongue, lips and peripheries) 2. Measured methaemoglobin saturation (using Masimo Rad-57 plus oximeter) \>15% 3. Measured oxygen saturation \<85%

Time frame: 12 months

Safety and Efficacy of Primaquine for P. Vivax

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts