Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Tolerability of Low Dose Primaquine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02434952
Recruitment Status : Completed
First Posted : May 6, 2015
Last Update Posted : August 23, 2016
Sponsor:
Collaborators:
National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Institute Pasteur, Cambodia
World Health Organization
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
Malaria Consortium

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Malaria, Falciparum G6PD Deficiency Drug: Dihydroartemisinin piperaquine (DHA PP) Drug: Primaquine Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Tolerability and Safety of Low Dose Primaquine for Transmission Blocking in Symptomatic Falciparum Infected Cambodians
Study Start Date : October 2014
Actual Primary Completion Date : July 2016


Arm Intervention/treatment
Experimental: DHA PP plus primaquine, G6PD deficiency

Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.

Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children <18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.

Drug: Dihydroartemisinin piperaquine (DHA PP)
Other Names:
  • Duo-Cotecxin
  • Eurartesim

Drug: Primaquine
Active Comparator: DHA PP plus primaquine, G6PD normal

Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.

Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children <18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.

Drug: Dihydroartemisinin piperaquine (DHA PP)
Other Names:
  • Duo-Cotecxin
  • Eurartesim

Drug: Primaquine
Active Comparator: DHA PP alone, G6PD deficiency
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
Drug: Dihydroartemisinin piperaquine (DHA PP)
Other Names:
  • Duo-Cotecxin
  • Eurartesim

Active Comparator: DHA PP alone, G6PD normal
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
Drug: Dihydroartemisinin piperaquine (DHA PP)
Other Names:
  • Duo-Cotecxin
  • Eurartesim




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02434952


Locations
Layout table for location information
Cambodia
Ratanakiri Provincial Hospital
Ratanakiri, Cambodia
Sponsors and Collaborators
Malaria Consortium
National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Institute Pasteur, Cambodia
World Health Organization
Centers for Disease Control and Prevention
Investigators
Layout table for investigator information
Principal Investigator: Dysoley Lek, MD National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Malaria Consortium
ClinicalTrials.gov Identifier: NCT02434952    
Other Study ID Numbers: 015NECHR
First Posted: May 6, 2015    Key Record Dates
Last Update Posted: August 23, 2016
Last Verified: August 2016
Keywords provided by Malaria Consortium:
Malaria, Falciparum
G6PD deficiency
Primaquine
Asia
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Malaria, Falciparum
Glucosephosphate Dehydrogenase Deficiency
Protozoan Infections
Parasitic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Piperaquine
Primaquine
Dihydroartemisinin
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents