Safety and Tolerability of Low Dose Primaquine

NCT02434952 | Completed Phase 4 DMC

• 1 other identifier: 015NECHR
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria, Falciparum; G6PD Deficiency

Keywords

Malaria, Falciparum; G6PD deficiency; Primaquine; Asia

Outcome Measures

Primary Outcomes (1)

• Haemoglobin concentration

  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

  Day 7

Secondary Outcomes (19)

• Determine G6PD enzyme activity

  Day 0

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

  Day 0

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

  Day 0

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

  Change from Day 0 to Day 7

• Plasma haemoglobin concentration as a marker of intravascular haemolysis

  Day 7

Study Arms (4)

DHA PP plus primaquine, G6PD deficiency

EXPERIMENTAL

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); Drug: Primaquine

DHA PP plus primaquine, G6PD normal

ACTIVE COMPARATOR

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); Drug: Primaquine

DHA PP alone, G6PD deficiency

ACTIVE COMPARATOR

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)

DHA PP alone, G6PD normal

ACTIVE COMPARATOR

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)

Interventions

Dihydroartemisinin piperaquine (DHA PP) DRUG

Also known as: Duo-Cotecxin, Eurartesim

DHA PP alone, G6PD deficiency; DHA PP alone, G6PD normal; DHA PP plus primaquine, G6PD deficiency; DHA PP plus primaquine, G6PD normal

Primaquine DRUG

DHA PP plus primaquine, G6PD deficiency; DHA PP plus primaquine, G6PD normal

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Ratanakiri Provincial Hospital

Ratanakiri, Ratanakiri, Cambodia

Location

Related Publications (2)

• 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.

  PMID: 32179526 DERIVED

• 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.

  PMID: 30871496 DERIVED

Related Links

• Malaria Consortium
• National Centre for Parasitology, Entomology and Malaria Control Program, Cambodia

MeSH Terms

Conditions

Malaria, Falciparum; Glucosephosphate Dehydrogenase Deficiency

Interventions

Primaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Dysoley Lek, MD

  National Centre for Parasitology, Entomology and Malaria Control, Cambodia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: May 6, 2015
• Study Start: October 1, 2014
• Primary Completion: July 1, 2016
• Last Updated: August 23, 2016

Record last verified: 2016-08

Locations

CA (1)