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Safety and Efficacy of Primaquine for P. Vivax

Primary Purpose

Malaria

Status
Unknown status
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Primaquine
delayed primaquine
Sponsored by
Menzies School of Health Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria

Eligibility Criteria

12 Months - 60 Years (Child, Adult)All SexesDoes not accept 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.

Sites / Locations

  • Tetere Hospital, Guadalcanal Province
  • Aoki Hospital, Malaita Province
  • Northern Provincial Hospital, Nambauk Aid Post, V.F.H.A Dispensary and Fanafo Dispensary
  • Toroa Dispensary, NTM Health Centre and Vila Central Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Other

Arm Label

Standard dose

High dose

Control

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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).
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).
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).
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
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%

Full Information

First Posted
March 25, 2013
Last Updated
November 7, 2013
Sponsor
Menzies School of Health Research
Collaborators
Walter and Eliza Hall Institute of Medical Research, Ministry of Health, Vanuatu, Ministry of Health, Solomon Islands, World Health Organization
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1. Study Identification

Unique Protocol Identification Number
NCT01837992
Brief Title
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

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Unknown status
Study Start Date
May 2013 (undefined)
Primary Completion Date
May 2014 (Anticipated)
Study Completion Date
May 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Menzies School of Health Research
Collaborators
Walter and Eliza Hall Institute of Medical Research, Ministry of Health, Vanuatu, Ministry of Health, Solomon Islands, World Health Organization

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard dose
Arm Type
Active Comparator
Arm 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.
Arm Title
High dose
Arm Type
Active Comparator
Arm 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.
Arm Title
Control
Arm Type
Other
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Primaquine
Intervention Type
Drug
Intervention Name(s)
delayed primaquine
Primary Outcome Measure Information:
Title
Efficacy: Numbers of Plasmodium vivax relapses per person-years of follow-
Description
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 Outcome Measure Information:
Title
Safety and toxicity (1): Numbers with mild adverse events
Description
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
Title
Safety and toxicity (2) Numbers with moderate adverse events
Description
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
Title
Safety and toxicity (3) Numbers with severe adverse events
Description
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
Title
Safety and toxicity (4) Numbers with any adverse events
Description
Numbers in each treatment arm experiencing any documented event (defined as either mild, moderate or severe as above).
Time Frame
12 months
Title
Safety and toxicity (5) Numbers with assumed significant haemolysis
Description
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
Time Frame
12 months
Title
Safety and toxicity (6) Numbers with significant methaemoglobinaemia
Description
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%
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ivo Mueller, PhD
Phone
+61 3 9345 2555
Email
mueller@wehi.edu.au
Facility Information:
Facility Name
Tetere Hospital, Guadalcanal Province
City
Honiara
State/Province
Guadalcanal Province
Country
Solomon Islands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lyndes Wini
First Name & Middle Initial & Last Name & Degree
Albino Bobogare
Facility Name
Aoki Hospital, Malaita Province
City
Auki
State/Province
Malaita Province
Country
Solomon Islands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Albino Bobogare
First Name & Middle Initial & Last Name & Degree
Lyndes Wini
Facility Name
Northern Provincial Hospital, Nambauk Aid Post, V.F.H.A Dispensary and Fanafo Dispensary
City
Luganville
State/Province
Sanma Province
Country
Vanuatu
Facility Contact:
First Name & Middle Initial & Last Name & Degree
George Taleo
First Name & Middle Initial & Last Name & Degree
Edward Tambisari
Facility Name
Toroa Dispensary, NTM Health Centre and Vila Central Hospital
City
Port Vila
State/Province
Shefa Province
Country
Vanuatu
Facility Contact:
First Name & Middle Initial & Last Name & Degree
George Taleo
First Name & Middle Initial & Last Name & Degree
Edward Tambisari, MD

12. IPD Sharing Statement

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Safety and Efficacy of Primaquine for P. Vivax

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