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Completed

NCT Number: NCT02434952

Safety and Tolerability of Low Dose Primaquine

In Cambodia, falciparum is becoming more difficult to treat because drugs are becoming less effective. The investigators can help to try to prevent the spread of this resistant malaria by adding a drug that will make it more difficult for the mosquito to drink up the malaria in people's blood. If the mosquito cannot drink up the malaria, then the malaria cannot develop in the mosquito so it will not be able to inject malaria back into people when it bites. The drug the investigators will use is called primaquine.

Primaquine commonly causes the red cells in the blood to break apart if they are weak. Red cells need enzymes to work properly and weak red cells have low amounts of an enzyme called glucose 6 phosphate dehydrogenase (G6PD). The investigators want to know if treating malaria with primaquine will be safe for the red cells. To do this study, the investigators need to know if a subject has low G6PD or not.

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Key information

Conditions

Malaria, Falciparum Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities G6PD Deficiency Genetic Diseases, Inborn Glucosephosphate Dehydrogenase Deficiency Hematologic Diseases Hemic and Lymphatic Diseases Infections Malaria Metabolic Diseases Metabolism, Inborn Errors Mosquito-Borne Diseases Nutritional and Metabolic Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

1 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Ratanakiri Provincial Hospital

Ratanakiri, Cambodia

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 1 year
  • Presentation with a confirmed fever (≥ 38⁰C axilla or ≥ 37.5⁰C aural) or history of fever in previous 48 hours +/- other clinical features of uncomplicated malaria
  • Plasmodium falciparum monoinfection ≥ 1 asexual form / 500 white blood cells
  • Informed consent (written/verbal) provided by patient or relative/legal guardian
  • Signed Assent form for children aged 12 to < 18 years

Exclusion criteria

  • Clinical signs of severe malaria or danger signs
  • Pregnant or breast feeding
  • Unable or unwilling to take a pregnancy test (for women of child-bearing age)
  • Women intending to become pregnant in the next 3 months
  • Allergic to primaquine or DHA PP
  • Patients taking drugs known to cause acute intravascular haemolytic anaemia (AIHA) in G6PD deficiency e.g. dapsone, nalidixic acid
  • Patients on treatment for a significant illness e.g. HIV, tuberculosis (TB) treatment, steroids
  • On drugs that could interfere with anti-malarial pharmacokinetics like antiretrovirals, cimetidine, ketoconazole, antiepileptic drugs, rifampicin

Treatment and study plan

Dihydroartemisinin piperaquine (DHA PP)

Drug

Other names: Duo-Cotecxin, Eurartesim

Primaquine

Drug

Primary outcomes

  1. Haemoglobin concentration

    Time frame: Day 7

    Compare haemoglobin concentrations in g/dL between the G6PD deficient arm given DHA PP plus primaquine, and the G6PD normal arm receiving the same regimen

Secondary outcomes

  1. Determine G6PD enzyme activity

    Time frame: Day 0

    Quantitative G6PD testing among all participants using the G6PD enzyme assay from Trinity Biologicals, USA, yielding G6PD enzyme results in U/g Hb.

  2. Assess usefulness of field adapted WHO haemoglobin colour card vs. Hemocue

    Time frame: Day 0

    Comparison of quantitative (HemoCue, g/dL HB) and qualitative (WHO haemolglobin colour card) estimates of haemoglobin concentration

  3. Assess usefulness of rapid test for G6PDd in predicting acute intravascular haemolysis

    Time frame: Day 0

    Comparison of rapid G6PD test (AccessBio, USA) qualitative result against quantitative G6PD assay to determine predictive value for clinically significant haemolysis

  4. Proportion patients with ≥25% change in haemoglobin as a marker of intravascular haemolysis

    Time frame: Change from Day 0 to Day 7

    Comparing across all 4 arms: proportion of all patients with fractional change in haemoglobin ≥25% from day 0 to day 7

  5. Plasma haemoglobin concentration as a marker of intravascular haemolysis

    Time frame: Day 7

    Comparing across all 4 arms: plasma haemoglobin concentration at day 7

  6. Urine colour change as a marker of intravascular haemolysis

    Time frame: Change from Day 0 to Day 7

    Change in urine colour grade from day 0 to day 7 (Hillmen, Hall et al. 2004)

  7. Fractional change in haemoglobin as a marker of intravascular haemolysis

    Time frame: Change from Day 0 to Day 7

    Comparing across all 4 arms: fractional change in haemoglobin on day 7 vs. day 0

  8. Clearance rate of primaquine

    Time frame: Day 0-7

    Primaquine elimination clearance rate, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ

  9. Half life of primaquine

    Time frame: Day 0-7

    Primaquine terminal elimination half life, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ

  10. Primaquine volume of distribution

    Time frame: Day 0-7

    Primaquine apparent volume of distribution (Vd), modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ

  11. Clearance rate of piperaquine

    Time frame: Day 0-28

    Piperaquine elimination clearance rate, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ

  12. Half life of piperaquine

    Time frame: Day 0-28

    Piperaquine terminal elimination half life, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ

  13. Piperaquine volume of distribution

    Time frame: Day 0-28

    Piperaquine apparent volume of distribution (Vd), modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ

  14. Peak plasma concentration (Cmax) of primaquine

    Time frame: Day 0-7

    Cmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ

  15. Peak plasma concentration (Cmax) of piperaquine

    Time frame: Day 0-28

    Cmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ

  16. Time to primquine peak plasma concentration (Tmax)

    Time frame: Day 0-7

    Tmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ

  17. Time to piperaquine peak plasma concentration (Tmax)

    Time frame: Day 0-28

    Tmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ

  18. Area under the plasma concentration versus time curve - primaquine

    Time frame: Day 0-7

    Modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ

  19. Area under the plasma concentration versus time curve - piperaquine

    Time frame: Day 0-28

    Modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ

Sponsors and collaborators

Lead sponsor

Malaria Consortium

Other

Collaborators

  • Centers for Disease Control and Prevention
  • Institute Pasteur, Cambodia
  • National Centre for Parasitology, Entomology and Malaria Control, Cambodia
  • World Health Organization

Registry information

Official study title

The Tolerability and Safety of Low Dose Primaquine for Transmission Blocking in Symptomatic Falciparum Infected Cambodians

Important dates

Study start
2014
Primary completion
2016
First posted
May 6, 2015
Registry last updated
Aug 23, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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