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Eight Week Primaquine Regimen for the Treatment of Vivax Malaria

Primary Purpose

Malaria, Vivax Malaria

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
primaquine
Sponsored by
London School of Hygiene and Tropical Medicine
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria focused on measuring Vivax, Treatment, Primaquine, Asia

Eligibility Criteria

3 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients diagnosed with P. vivax parasitaemia Patients over 3 years Patients with G6PD deficiency to a safety trial Patients without G6PD deficiency to all other groups. Exclusion Criteria: Children under the age of three Pregnant / breast feeding women Patients with severe clinical anaemia [Hb<7g/dl] Patients with P. falciparum Patients unavailable for the duration of study. Patients who have taken antimalarial drugs in the 2 weeks prior to consultation. Patients with concomitant infections or whose general health is considered too poor.

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Primary Efficacy Variable: Proportion with relapse(s) of P. vivax in 12 months of follow-up.

    Secondary Outcome Measures

    Secondary Efficacy Variables: Time to subsequent relapse episode
    Number of relapse episodes in 12 months
    Side effects / adverse events

    Full Information

    First Posted
    September 9, 2005
    Last Updated
    January 11, 2017
    Sponsor
    London School of Hygiene and Tropical Medicine
    Collaborators
    HealthNet TPO
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00158587
    Brief Title
    Eight Week Primaquine Regimen for the Treatment of Vivax Malaria
    Official Title
    A Placebo Controlled, Randomised Evaluation of an Eight Week Primaquine Regimen for the Treatment of Vivax Malaria.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2004 (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    March 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    London School of Hygiene and Tropical Medicine
    Collaborators
    HealthNet TPO

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Plasmodium vivax represents a major health problem throughout the tropics. Outside Africa it accounts for over 50% of cases, affecting an estimated 70-80 million people per year. A substantial proportion of clinical cases are not caused by infective bites of Anopheles spp, but by activation of latent hypnozoites in the liver. These relapses may significantly impede development since each illness may result in 5-15 days of absence from work or school. Primaquine(PQ) is the only drug available that eliminates hypnozoites, though its use is beset by clinical problems; it may precipitate haemolytic anaemia in individuals deficient in the blood enzyme glucose 6 phosphate dehydrogenase (G6PD). Without affordable G6PD testing, primaquine use is precluded. Evidence suggests, however, that a course of 8 weekly doses may be a safe and effective alternative to the traditional 14 day course of the drug. The aim of the proposed study, therefore, is to test whether 8 weekly doses of primaquine is as effective as the 14 day course at preventing relapse malaria, without the risk of hemolysis in G6PD deficient individuals.
    Detailed Description
    Old evidence suggests that successful PQ therapy is not a function of the length of the course of treatment, nor the circulating concentration of the drug, but of the total dosage administered. The same dose administered over 7 days, 14 days, and 8 weeks equally prevented relapse in vivax malaria. The hemolysis seen in shorter courses is often self-limiting, suggesting that feedback mechanisms up-regulate production of red cells in response to haemolytic challenge. The proposed extended course is likely to be well tolerated in G6PD deficient individuals as a result of these safeguards, especially in this population which has been exposed to the 5 day PQ regimen for a number of years without reported adverse effects. The aim of the study, therefore, is to test whether an 8 week regimen proves effective, without the associated risk of haemolysis in G6PD deficient individuals. However, operational concerns remain about adherence to this protracted treatment regimen. Therefore we will compare the 8 week course in 2 different groups; the first to be directly observed dosing, the second to be unsupervised dosing using pre-packaged, foil wrapped PQ in appropriately labelled individual boxes, supplied with strong health education messages. This would be appropriate for deployment in a resource-poor setting if it proved effective and safe. Objectives: To evaluate whether an eight week primaquine regimen, using single weekly doses, can provide adequate radical cure of vivax malaria under experimental and operational conditions and is safe in and acceptable to a population with glucose 6 phosphate dehydrogenase deficiency. The specific objectives of the study are set out below. Determine the efficacy of an eight-week primaquine regime, using single weekly doses, in preventing relapses of P. vivax infections following supervised versus unsupervised administration of the drug. Compare the efficacy and operational aspects (e.g. adherence) between the two week, eight week supervised and eight week blister package regimes. Monitoring of the effect of 8 week PQ on G6PD deficient individuals. Examine the user acceptability and economic advantages of this course of treatment. Study population: Vivax positive individuals from Adizai and Baghicha refugee camps, Pakistan, and Jalalabad, Afghanistan. Laboratory Examination: All suspected malaria cases attending basic health units will have thick and thin blood films taken and examined by conventional light microscopy. Cases diagnosed with P. vivax infection will be asked to participate in the study unless the exclusion criteria are met. All patients will then be tested for G6PD deficiency by near patient testing. The test is a colorimetric qualitative test for G6PD in red cells requiring 0.05 ml of blood. In addition, a filter paper blood spot will be collected to allow molecular typing of the parasite. This will differentiate between a new and a relapse infection. Design Randomised placebo controlled study comparing the following four study groups: Initial 3 day chloroquine with supervised weekly placebo for 8 weeks. Initial 3 day chloroquine followed by supervised 14 day primaquine treatment. Initial 3 day chloroquine followed by supervised 8 week primaquine treatment (45 mg / week). All patients will be given health education messages and strongly advised to complete the course. In addition a safety arm will be used for G6PD deficient patients; this will be used to compare PCV with group 3 (above). This will be an 8 week regimen, administered by direct observation, and will receive close monitoring for haemolysis. Treatment: All patients will be given a full therapeutic course of chloroquine. Primaquine will be administered to the study groups according to the respective protocol schedule. All relapses and new cases will be re-treated using the same regime and procedure as at the time of admission. Monitoring: Patients in treatment groups 1, 2, and 3 will be monitored for the initial 8 weeks of treatment for adverse events; G6PD deficient patients will be monitored for signs of hemolysis every other day for the first 2 weeks of treatment and then once per week (prior to dosing) until completion of the course. Following the treatment period, patients will be monitored for 1 year for the following outcomes: Primary Efficacy Variable: Proportion with relapse(s) of P. vivax in 12 months of follow-up. Secondary Efficacy Variables: Time to subsequent relapse episode, number of relapse episodes in 12 months, side effects / adverse events Patients will be advised to return to the BHU in the event of recurrent symptoms within 12 months following enrolment to the study. A patient will be deemed to have completed the study after 12 months of follow-up. In any event each patient will be contacted once every 2 weeks during the follow-up period in order to collect relevant information. At each episode, a sample of blood will allow molecular typing of the parasite and define whether the patient has a new infection or a relapse.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Malaria, Vivax Malaria
    Keywords
    Vivax, Treatment, Primaquine, Asia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    150 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    primaquine
    Primary Outcome Measure Information:
    Title
    Primary Efficacy Variable: Proportion with relapse(s) of P. vivax in 12 months of follow-up.
    Time Frame
    2004-March 2007
    Secondary Outcome Measure Information:
    Title
    Secondary Efficacy Variables: Time to subsequent relapse episode
    Time Frame
    2004-March 2007
    Title
    Number of relapse episodes in 12 months
    Time Frame
    2004-March 2007
    Title
    Side effects / adverse events
    Time Frame
    2004-March 2007

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients diagnosed with P. vivax parasitaemia Patients over 3 years Patients with G6PD deficiency to a safety trial Patients without G6PD deficiency to all other groups. Exclusion Criteria: Children under the age of three Pregnant / breast feeding women Patients with severe clinical anaemia [Hb<7g/dl] Patients with P. falciparum Patients unavailable for the duration of study. Patients who have taken antimalarial drugs in the 2 weeks prior to consultation. Patients with concomitant infections or whose general health is considered too poor.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Mark Rowland, PhD
    Organizational Affiliation
    LSHTM
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    18682739
    Citation
    Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, Rowland M. A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of plasmodium vivax in Northwest Frontier Province, Pakistan. PLoS One. 2008 Aug 6;3(8):e2861. doi: 10.1371/journal.pone.0002861.
    Results Reference
    derived

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    Eight Week Primaquine Regimen for the Treatment of Vivax Malaria

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