Safety and Efficacy of Primaquine for P. Vivax

Malaria Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01837992
• Other study ID #: VanSI_2013
• Status: Not yet recruiting
• Phase: N/A
• First received: March 25, 2013
• Last updated: November 7, 2013
• Start date: May 2013
• Est. completion date: May 2015

Study information

• Verified date: November 2013
• Source: Menzies School of Health Research
• Contact: Ivo Mueller, PhD
• Phone: +61 3 9345 2555
• Email: mueller[@]wehi.edu.au
• Is FDA regulated: No
• Health authority: Australia: Menzies School of Health ResearchAustralia: Walter and Eliza Hall InstituteAustralia: Western HealthVanuatu: Ministry of HealthVanuatu: World Health OrganizationSolomon Islands: Ministry of HealthSolomon Islands: World Health OrganizationPhilippines: World Health Organization
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 180
• Est. completion date: May 2015
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Primaquine

• delayed primaquine

Locations

Country	Name	City	State
Solomon Islands	Aoki Hospital, Malaita Province	Auki	Malaita Province
Solomon Islands	Tetere Hospital, Guadalcanal Province	Honiara	Guadalcanal Province
Vanuatu	Northern Provincial Hospital, Nambauk Aid Post, V.F.H.A Dispensary and Fanafo Dispensary	Luganville	Sanma Province
Vanuatu	Toroa Dispensary, NTM Health Centre and Vila Central Hospital	Port Vila	Shefa Province

Sponsors (5)

Lead Sponsor	Collaborator
Menzies School of Health Research	Ministry of Health, Solomon Islands, Ministry of Health, Vanuatu, Walter and Eliza Hall Institute of Medical Research, World Health Organization

Countries where clinical trial is conducted

Solomon Islands,  Vanuatu, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months	No
Secondary	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).	12 months	Yes
Secondary	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).	12 months	Yes
Secondary	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).	12 months	Yes
Secondary	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).	12 months	Yes
Secondary	Safety and toxicity (5) Numbers with assumed significant haemolysis	Numbers in each treatment arm experiencing any of the following: Haemoglobinuria on dipstick examination; Scleral icterus; Haemoglobin concentration fall by more than 25% of baseline or absolute concentration <5g/dL	12 months	Yes
Secondary	Safety and toxicity (6) Numbers with significant methaemoglobinaemia	Numbers in each treatment arm experiencing any of the following: Cyanosis (blue tongue, lips and peripheries); Measured methaemoglobin saturation (using Masimo Rad-57 plus oximeter) >15%; Measured oxygen saturation <85%	12 months	Yes