Antimalarial Drug Susceptibility and Molecular Characterization of Plasmodium Vivax Isolates in Vietnam

Study Overview
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Brief Summary
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This is a study of drug effectiveness for 2 treatments of vivax malaria, which is one of the two main types of malaria in Viet Nam. There are two important drugs used in Viet Nam for treating vivax malaria, Chloroquine and Artemisinin. Sometimes, when medicines are used for many years they become less effective at treating a disease, especially when they are not used at adequate doses according to national guidelines or when counterfeit drugs are available in the market. The purpose of this study is to check that Chloroquine and Artemisinin, are still effective for patients in Viet Nam. Participants in this study will be treated with either Dihydroartemisinin-Piperaquine (DHA-PPQ) or Chloroquine (CQ) for 3 days. Both drugs are recommended by the national guidelines to treat vivax malaria. The investigators would like to know if both of these treatments are equally effective so half of the patients in the study will be treated with DHA-PPQ and the other half will be treated with CQ. This way the investigators can compare the drugs to find out if one is better than the other. Participants will be followed for 3 days in hospital, then regularly by follow-up visits until the 63rd day. Tests will be done to determine the amount of drug and malaria parasites in the participant's body and how the blood cells react to the malaria. The parasite will be tested to determine what type it is and how it reacts to the treatment. The results of the study will be used to inform malaria treatment guidelines in Viet Nam.

Official Title
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A Randomised Controlled Trial to Assess the Antimalarial Drug Susceptibility and Molecular Characterization of Plasmodium Vivax Isolates in Vietnam

Conditions
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Plasmodium Vivax Malaria

Intervention / Treatment
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* Drug: Chloroquine
* Drug: Dihydroartemisinin/Piperaquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 3 years; Mono-infection with P. vivax, parasitemia > 250/µl asexual forms for in vivo and >8000 asexual parasites/µl blood for in vitro testing; Presence of axillary or tympanic temperature ≥ 37.5 °C or history of fever during the past 24 h; Ability to swallow oral medication; Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; Informed consent/assent Exclusion Criteria: Presence of general danger signs or severe malaria according to the definitions of WHO (2000); Mixed infection with P.falciparum and P.vivax of other plasmodium species; Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS); Regular medication, which may interfere with antimalarial pharmacokinetics; Received antimalarial drugs in the previous 48 hours; History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s); Splenectomy; First trimester of pregnancy.

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chloroquine<br>25mg base/kg for 3 days | Drug: Chloroquine<br> <br> |
| Active Comparator: Dihydroartemisinin/Piperaquine<br>Dihydroartemisinin 40 mg + piperaquine phosphate 320 mg per tablet; once daily for three days, doses depend on weight | Drug: Dihydroartemisinin/Piperaquine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with adequate response to treatment | Adequate response = adequate clinical and parasitological response. Absence of parasitaemia on day 63, irrespective of temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure. | Day 63 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients classified as Early Treatment Failures | One or more of the following: danger signs or severe malaria on day 1, 2 or 3 in the presence of parasitaemia; parasitaemia on day 2 higher than on day 0, irrespective of temperature; parasitaemia on day 3 with temperature ≥ 37.5 ºC; parasitaemia on day 3 ≥ 25% of count on day 0. | Day 63 | 
| The parasite clearance time | Defined as the time in hours from the first treatment dose to the first of two consecutive parasitemia counts of zero. | Assessed every 6 hours until Day 3, or two consecutive parasite negative slides. | 
| Fever clearance time | Defined as the time in hours from the first treatment dose to the start of the first sustained period of 24 hours without fever | Assessed every 6 hours until Day 3, or 24 hours without fever | 
| Frequency of adverse and serious adverse events |  | Day 63 | 
| Proportion of patients classified as Late Clinical Failures | One or more of the following: danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 63 in patients who did not previously meet any of the criteria of early treatment failure; presence of parasitaemia on any day between day 4 and day 63 with temperature ≥ 37.5 ºC (or history of fever) in patients who did not previously meet any of the criteria of early treatment failure | Day 63 | 
| Proportion of patients classified as Late Parasitological Failures | Presence of parasitaemia on any day between day 7 and day 63 with temperature < 37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure | Day 63 |