Safety and Efficacy of Primaquine for P. Vivax

November 7, 2013 updated by: Menzies School of Health Research

Evaluation of Safety and Efficacy of Two Primaquine Dosing Regimens for the Radical Treatment of Plasmodium Vivax Malaria in Vanuatu and Solomon Islands

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
180

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 56 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard dose
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.
Drug: Primaquine
Active Comparator: High dose
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.
Drug: Primaquine
Other: Control
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.
Drug: delayed primaquine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy: Numbers of Plasmodium vivax relapses per person-years of follow-
Time Frame: 12 months
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety and toxicity (1): Numbers with mild adverse events
Time Frame: 12 months
Numbers in each treatment arm experiencing any documented adverse event defined as "mild" (not severe enough to interfere with daily activities).
12 months
Safety and toxicity (2) Numbers with moderate adverse events
Time Frame: 12 months
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
Safety and toxicity (3) Numbers with severe adverse events
Time Frame: 12 months
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
Safety and toxicity (4) Numbers with any adverse events
Time Frame: 12 months
Numbers in each treatment arm experiencing any documented event (defined as either mild, moderate or severe as above).
12 months
Safety and toxicity (5) Numbers with assumed significant haemolysis
Time Frame: 12 months

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
12 months
Safety and toxicity (6) Numbers with significant methaemoglobinaemia
Time Frame: 12 months

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%
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Menzies School of Health Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
World Health Organization
Walter and Eliza Hall Institute of Medical Research
Ministry of Health, Vanuatu
Ministry of Health, Solomon Islands

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2013

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2014

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 25, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 23, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 8, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VanSI_2013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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