Clinical trial NCT02434952: Safety and Tolerability of Low Dose Primaquine
Official title: The Tolerability and Safety of Low Dose Primaquine for Transmission Blocking in Symptomatic Falciparum Infected Cambodians
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria, Falciparum
G6PD Deficiency
Keywords: Malaria, Falciparum
G6PD deficiency
Primaquine
Asia
Lead sponsor: Malaria Consortium
Sponsor class: OTHER
Collaborators: name: National Centre for Parasitology, Entomology and Malaria Control, Cambodia
name: Institute Pasteur, Cambodia
name: World Health Organization
name: Centers for Disease Control and Prevention
First posted: 2015-05-06
Enrollment: 109
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Haemoglobin concentration
timeFrame: Day 7
Secondary outcomes:
measure: Determine G6PD enzyme activity
timeFrame: Day 0
measure: Assess usefulness of field adapted WHO haemoglobin colour card vs. Hemocue
timeFrame: Day 0
measure: Assess usefulness of rapid test for G6PDd in predicting acute intravascular haemolysis
timeFrame: Day 0
measure: Proportion patients with ≥25% change in haemoglobin as a marker of intravascular haemolysis
timeFrame: Change from Day 0 to Day 7
measure: Plasma haemoglobin concentration as a marker of intravascular haemolysis
timeFrame: Day 7
measure: Urine colour change as a marker of intravascular haemolysis
timeFrame: Change from Day 0 to Day 7
measure: Fractional change in haemoglobin as a marker of intravascular haemolysis
timeFrame: Change from Day 0 to Day 7
measure: Clearance rate of primaquine
timeFrame: Day 0-7
measure: Half life of primaquine
timeFrame: Day 0-7
measure: Primaquine volume of distribution
timeFrame: Day 0-7
measure: Clearance rate of piperaquine
timeFrame: Day 0-28
measure: Half life of piperaquine
timeFrame: Day 0-28
measure: Piperaquine volume of distribution
timeFrame: Day 0-28
measure: Peak plasma concentration (Cmax) of primaquine
timeFrame: Day 0-7
measure: Peak plasma concentration (Cmax) of piperaquine
timeFrame: Day 0-28
measure: Time to primquine peak plasma concentration (Tmax)
timeFrame: Day 0-7
measure: Time to piperaquine peak plasma concentration (Tmax)
timeFrame: Day 0-28
measure: Area under the plasma concentration versus time curve - primaquine
timeFrame: Day 0-7
measure: Area under the plasma concentration versus time curve - piperaquine
timeFrame: Day 0-28
Other outcomes:
Locations:
city: Ratanakiri
country: Cambodia
facility: Ratanakiri Provincial Hospital
Study officials:
affiliation: National Centre for Parasitology, Entomology and Malaria Control, Cambodia
name: Dysoley Lek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vantaux A, Kim S, Piv E, Chy S, Berne L, Khim N, Lek D, Siv S, Mukaka M, Taylor WR, Menard D. Significant Efficacy of a Single Low Dose of Primaquine Compared to Stand-Alone Artemisinin Combination Therapy in Reducing Gametocyte Carriage in Cambodian Patients with Uncomplicated Multidrug-Resistant Plasmodium falciparum Malaria. Antimicrob Agents Chemother. 2020 May 21;64(6):e02108-19. doi: 10.1128/AAC.02108-19. Print 2020 May 21.
citation: Dysoley L, Kim S, Lopes S, Khim N, Bjorges S, Top S, Huch C, Rekol H, Westercamp N, Fukuda MM, Hwang J, Roca-Feltrer A, Mukaka M, Menard D, Taylor WR. The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians. BMC Infect Dis. 2019 Mar 12;19(1):250. doi: 10.1186/s12879-019-3862-1.