Gametocytocidal and Transmission-blocking Efficacy of ASAQ and ALAQ With or Without PQ in Mali (NECTAR4)

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 2

Conditions: Malaria,Falciparum

Treatments: Drug: Primaquine Phosphate; Drug: Artesunate-amodiaquine combination; Drug: Artemether-lumefantrine; Drug: Amodiaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT05550909

28041

Details and patient eligibility

About

The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine-amodiaquine (ALAQ) with and without a single dose of 0.25mg/kg primaquine (PQ). Outcome measures will include infectivity to mosquitoes at 2, 7 and 14 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density and the frequency of adverse events.

Full description

Full protocol available on request

Enrollment: 100 patients

Sex: All

Ages: 10 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age ≥ 10 years and ≤ 50 years
• Absence of symptomatic falciparum malaria, defined by fever on enrolment
• Presence of P. falciparum gametocytes on thick blood film at a density >16 gametocytes/µL (i.e. ≥ gametocytes recorded in the thick film against 500 white blood cells)
• Absence of other non-P. falciparum species on blood film
• Haemoglobin ≥ 10 g/dL
• Individuals weighing < = 80 kg
• No evidence of acute severe or chronic disease
• Written, informed consent

Exclusion criteria

• Women who are pregnant or lactating (tested at baseline). Urine and/or serum pregnancy testing (β-hCG) will be used.
• Detection of a non-P. falciparum species by microscopy
• Previous reaction to study drugs / known allergy to study drugs, such as sudden high fevers, shaking or severe sore throat or ulcers in the mouth during treatment with Amodiaquine
• Current eye disease with retinal damage
• Signs of severe malaria, including hyperparasitaemia (defined as asexual parasitaemia > 100,000 parasites / µL)
• Signs of acute or chronic illness, including hepatitis
• The use of other medication (except for paracetamol and/or aspirin), including antacids, other medicines used to treat malaria, abnormal heart rhythm, depression or mental illness or HIV/AIDS, and medicines that have antibiotic/antifungal properties
• Use of antimalarial drugs over the past 7 days (as reported by the participant)
• Clinically significant illness (intercurrent illness e.g., pneumonia, pre-existing condition e.g., renal disease or HIV/AIDS, malignancy or conditions that may affect absorption of study medication e.g., severe diarrhoea or any signs of malnutrition as defined clinically)
• Signs of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e., decompensated cirrhosis, Child Pugh stage B or C)
• Signs, symptoms or known renal impairment
• Clinically significant abnormal laboratory values as determined by history, physical examination, or routine blood chemistries and haematology values (laboratory guideline values for exclusion are haemoglobin < 10 g/dL, platelets < 50,000/μl, White Blood Cell count (WBC) < 2000/μl, serum creatinine >2.0mg/dL, or ALT more than 3 times the upper limit of normal for age.
• Blood transfusion in the last 90 days.
• Known Electrocardiogram (ECG) corrected QT interval of more than 450 ms
• Documented or self-reported history of cardiac conduction problems
• Documented or self-reported history of epileptic seizures

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 5 patient groups

artesunate-amodiaquine (ASAQ)

Active Comparator group

Description:

Subjects will receive artesunate-amodiaquine (ASAQ) daily for 3 days.

Treatment:

Drug: Artesunate-amodiaquine combination

ASAQ with 0.25mg/kg primaquine (PQ)

Experimental group

Description:

Subjects will receive artesunate-amodiaquine (ASAQ) daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ASAQ treatment.

Treatment:

Drug: Artesunate-amodiaquine combination

Drug: Primaquine Phosphate

Artemether-Lumefantrine (AL)

Active Comparator group

Description:

Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days.

Treatment:

Drug: Artemether-lumefantrine

Artemether-Lumefantrine-Amodiaquine (ALAQ)

Experimental group

Description:

Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days.

Treatment:

Drug: Amodiaquine

Drug: Artemether-lumefantrine

Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)

Experimental group

Description:

Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ALAQ treatment.

Treatment:

Drug: Amodiaquine

Drug: Artemether-lumefantrine

Drug: Primaquine Phosphate