Dihydroartemisinin-piperaquine With Low Dose Primaquine to Reduce Malaria Transmission

NCT ID: NCT02259426

Last Updated: 2016-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2015-12-31

Brief Summary

Primaquine (PQ) is currently the only available drug that can clear the mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. A major caveat to the use of primaquine in mass adminsitrations for the reduction of malaria transmission is that metabolism of the drug in individuals with glucose-6 phosphate dehydrogenase (G6PD) deficiency can lead to transient haemolysis. The haemolytic side effect of PQ is dose-related. Haemolysis is more commonly observed after prolonged PQ treatment but has also been observed in African populations following a single dose of PQ. This haemolysis was self-limiting, largely restricted to G6PD deficient individuals and did not lead to clinical symptoms. Nevertheless, any drug-induced haemolysis is reason for concern and the World Health Organization has therefore reduced the recommended dose of single low dose primaquine from 0.75mg/kg to 0.25mg/kg. This dosage is deemed safe without prior G6PD or Hb screening. However, there is limited direct evidence on the extent to which this dosage of PQ prevents malaria transmission to mosquitoes.

In the current study, the investigators will assess the efficacy of DP in combination with low-dose PQ to prevent onward malaria transmission. The investigators will perform the investigators study in individuals aged 5-15 years who are carry microscopically detectable densities of P. falciparum gametocytes. This age group is chosen because asexual parasite carriage and gametocyte carriage are common in this age group. All enrolled individuals will receive a full three-day course of DP, and will be randomized to receive a dose of primaquine or placebo with their third dose. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For all individuals, the effect of treatment on infectivity to mosquitoes will be assessed by membrane feeding assays at two time points.

Conditions

Malaria; Asymptomatic Malaria; Plasmodium Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dihydroartemisínin-piperaquine (Artekin)

Dihydroartemisínin-piperaquine combination alone

Group Type: ACTIVE_COMPARATOR

Dihydroartemisinin-piperaquine combination (Artekin)

Intervention Type: DRUG

Dihydroartemisinin-piperaquine, Primaquine

Dihydroartemisinin-piperaquine with single-dose 0.25mg/kg Primaquine

Group Type: EXPERIMENTAL

Dihydroartemisinin-piperaquine combination (Artekin)

Intervention Type: DRUG

Primaquine

Intervention Type: DRUG

Single-dose 0.25mg/kg

Interventions

Dihydroartemisinin-piperaquine combination (Artekin)

Intervention Type: DRUG

Primaquine

Single-dose 0.25mg/kg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Microscopically detectable P. falciparum gametocyte carriage

Exclusion Criteria

• Age < 5 years or > 15 years
• Non-falciparum malaria co-infection
• Malaria parasite density ≥ 200,000 parasites/µL
• Clinical symptoms indicating severe malaria
• Axillary temperature ≥ 39°C
• Body Mass Index (BMI) below 16 or above 32 kg/m2
• Haemoglobin concentration below 9.5 g/dL
• Anti-malarials taken in last 2 days
• For women: Pregnancy (assessed by clinical examination and urine pregnancy test) or lactation
• Known hypersensitivity to DP or PQ
• History and/or symptoms indicating chronic illness
• Current use of tuberculosis or anti-retroviral medication
• Unable to give written informed consent
• Unwillingness to participate in two membrane feeding assays
• Travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, - Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan
• Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
• Taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes - macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole) and cisapride
• Known disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia
• Taking drugs which may be metabolized by cytochrome enzyme CYP2D6 (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine)
• Blood transfusion within last 90 days

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

International Centre of Insect Physiology and Ecology (ICIPE)

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teun Bousema, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud university medical center, London School of hygiene and tropical medicine

Patrick Sawa, MD

Role: PRINCIPAL_INVESTIGATOR

ICIPE

Locations

ICIPE

Mbita, Nyanza, Kenya

Countries

Kenya

Other Identifiers

DAPPI-1

Identifier Type: -

Identifier Source: org_study_id