Clinical trial NCT01837992: Safety and Efficacy of Primaquine for P. Vivax
Official title: Evaluation of Safety and Efficacy of Two Primaquine Dosing Regimens for the Radical Treatment of Plasmodium Vivax Malaria in Vanuatu and Solomon Islands
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Malaria
Lead sponsor: Menzies School of Health Research
Sponsor class: OTHER
Collaborators: name: Walter and Eliza Hall Institute of Medical Research
name: Ministry of Health, Vanuatu
name: Ministry of Health, Solomon Islands
name: World Health Organization
First posted: 2013-04-23
Enrollment: 180
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy: Numbers of Plasmodium vivax relapses per person-years of follow-
timeFrame: 12 months
Secondary outcomes:
measure: Safety and toxicity (1): Numbers with mild adverse events
timeFrame: 12 months
measure: Safety and toxicity (2) Numbers with moderate adverse events
timeFrame: 12 months
measure: Safety and toxicity (3) Numbers with severe adverse events
timeFrame: 12 months
measure: Safety and toxicity (4) Numbers with any adverse events
timeFrame: 12 months
measure: Safety and toxicity (5) Numbers with assumed significant haemolysis
timeFrame: 12 months
measure: Safety and toxicity (6) Numbers with significant methaemoglobinaemia
timeFrame: 12 months
Other outcomes:
Locations:
city: Honiara
country: Solomon Islands
facility: Tetere Hospital, Guadalcanal Province
state: Guadalcanal Province
city: Auki
country: Solomon Islands
facility: Aoki Hospital, Malaita Province
state: Malaita Province
city: Luganville
country: Vanuatu
facility: Northern Provincial Hospital, Nambauk Aid Post, V.F.H.A Dispensary and Fanafo Dispensary
state: Sanma Province
city: Port Vila
country: Vanuatu
facility: Toroa Dispensary, NTM Health Centre and Vila Central Hospital
state: Shefa Province
Study officials:
References: