Artemisinin-based Combination Therapy for Treatment of Plasmodium Falciparum Malaria in North Sumatera, Indonesia

London School of Hygiene and Tropical Medicine338 enrolled

Overview

This is a prospective, open label, randomised controlled trial to assess the safety and efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria infection. Molecular markers for antimalarial resistance will also be assessed and the presence of molecular markers in the parasites will be associated with treatment outcomes.

Artemisinin-based combination therapy (ACT) is the current recommended treatment by WHO for uncomplicated falciparum malaria. It is highly effective with few adverse effects. The artemisinin component is combined with a partner drug with a longer half-life to ensure the clearance of the remaining parasites after rapid reduction by artemisinin. ACT is used as first-line treatment for uncomplicated P. falciparum infection in Indonesia since 2004. There are 3 combinations available in the country including artesunate-amodiaquine (AS-AQ), dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL). Studies at different sites across Indonesia have shown various efficacy. Yet, there is an increased concern of reduced susceptibility of P. falciparum to artemisinin in neighbouring countries. Therefore, there is a need to evaluate and monitor the efficacies of these combinations in Indonesia. Molecular markers are an important tool for detecting and monitoring the presence of antimalarial resistance. Their significant implication is to geographically map the extent of resistant-parasites, thus enabling strategies for their control and elimination to be applied before the inevitably increase in the disease burden occurs. Different markers have been used to identify antimalarial resistance and recently a molecular marker for artemisinin susceptibility in P. falciparum has also been proposed. The presence of these markers in parasites from our study will also be investigated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

338

Conditions

Malaria, Falciparum

Interventions

Dihydroartemisinin-PiperaquineDRUG

Artemether-lumefantrineDRUG

Eligibility

Sex: ALLMin age: 6 Months

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female * All patients per 6 months of age * Fever as defined by axillary temperature \> 37.5 C or history of fever during the 48 hours before recruitment * Infection with P. falciparum detected by microscopy * Parasitaemia \> 250 /uL blood * Ability to swallow oral medication * Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule * Informed consent from the patient or from a parent or guardian in the case of children * Absence of history to hypersensitive reactions or contraindication to antimalarial drugs * Not currently consuming antibiotic with antimalarial activity (such as cotrimoxazole, macrolides, tetracycline or doxycycline) Exclusion Criteria: * Presence of general danger signs in children under 5 years or signs of severe falciparum malaria according to the definitions of WHO (2000) * Presence of severe malnutrition according to WHO child growth standards * Presence of febrile conditions caused by diseases other than malaria * Presence of severe anemia (Hemoglobin \< 7 gr/dL) * Received any of the study drugs within the past 4 weeks * Received any antimalarial within the last 2 weeks * Recurrent vomiting )necessitating more than a single repeat dose) * Pregnant (demonstrated by positive result of b-HCG in women of childbearing age * Lactating mother

Locations (3)

Primary health centres

Kuala Langkat, North Sumatera, Indonesia

Primary health centres

Tanjung Tiram, North Sumatera, Indonesia

Pulau-pulau Batu health centres

Tello Island, North Sumatera, Indonesia

Outcomes

Primary Outcomes

Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine

Early treatment failure, late treatment failure, adequate clinical and parasitological response Proportion of participants with Adequate Clinical and Parasitological Response

Time frame: 42 days

Secondary Outcomes

Parasite clearance times

Parasite reduction ratio, parasite clearance half-life

Time frame: 3 days

Fever clearance times

Time frame: 3 days

Prevalence of molecular markers and the impact on treatment outcomes

Pfcrt, Pfmdr1, Pfk13 and any other important molecular markers

Time frame: 42 days

Prevalence of gametocyte

Proportion of patients with gametocyte

Time frame: 42 days

Presence of other Plasmodium species

Plasmodium vivax, Plasmodium malariae, Plasmodium ovale spp, Plasmodium knowlesi

Time frame: 42 days

Haematological recovery

Haemoglobin

Time frame: 28 days

Data from ClinicalTrials.gov

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