Study of Malaria Treatment at Phuoc Long Hospital, Binh Phuoc Province, Vietnam
Clinical Investigation of In-vivo Susceptibility of P. Falciparum to Artesunate in Phuoc Long Hospital, Binh Phuoc Province, Vietnam
Background: There are worrying signs from Western Cambodia that parasitological responses to artesunate containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world. Delayed parasite clearance and unusually high failure rates with artesunate-mefloquine have been reported. These antimalarials are central to current treatment strategies and spread of significant resistance outside this area would be a global disaster. Radical containment measures are needed. In this context there is an urgent need to proceed quickly to investigate whether there is any evidence of resistance to artemisinin derivatives in Vietnam.
Objective: The primary objective is to assess the slope of the decline in the log parasitemia-time curve in patients treated with artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily, and to compare the results of this study to the pharmacokinetic results and to the recent data from patients in Cambodia and Thailand treated with equivalent therapies.
Methods: The trial will be conducted in Phuoc Long Hospital, Binh Phuoc Province, Vietnam. The participants will be febrile patients (aged > 10 years) with slide confirmed uncomplicated P. falciparum infection. Patients will be treated with either artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily for 3 days. Patients on artesunate therapy arms will then receive 3 days of treatment with dihydroartemisinin-piperaquine with dosages according to the national guidelines. Clinical and parasitological parameters will be monitored over a 42-day follow-up period. The pharmacokinetic characteristics of artesunate and dihydroartemisinin will be assessed by using a population pharmacokinetic modeling.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Binh Phuoc
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Dong Xoai, Binh Phuoc, Vietnam, 84
- Phuoc Long Hospital
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- male and aged > 10 years OR;
- female patients > 10 and <12 years old, provided they have not reached menarche
- mono-infection with P. falciparum detected by microscopy;
- parasitaemia of 10,000 - 100,000/µl asexual forms;
- 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 falciparum malaria according to the definitions of WHO;
- mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe malnutrition (defined as a child whose growth standard is below -3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm);
- 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;
- treatment with 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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Faculteitstoewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: Artesunate 2mg
People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with artesunate 2mg/kg/day for 3 days and followed by DHA-PPQ treatment at doses according to National guidelines for 3 days.
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artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily
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Experimenteel: Artesunate 4mg
People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with artesunate 4mg/kg/day for 3 days and followed by DHA-PPQ treatment at doses according to National guidelines for 3 days.
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artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily
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Experimenteel: DHA-piperaquine
People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with dihydroartemisinin-piperaquine once daily according to weight for 3 days.
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artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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Slope of the decline in the log parasitemia-time curve relative to historical data
Tijdsspanne: 03 days
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03 days
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Clearance rate assessed from the fitted slope of the log-linear parasite curves
Tijdsspanne: 72 hours
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72 hours
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Proportion of patients who have a parasite clearance time >72 hours after initiation of each treatment
Tijdsspanne: 72 hours
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72 hours
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Parasitological efficacy of the three treatment arms
Tijdsspanne: Over 72 hours and during follow-up treatment over a total follow-up period of 42 days
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Over 72 hours and during follow-up treatment over a total follow-up period of 42 days
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Relative proportion of patients treated with artesunate 2mg/kg/day versus artesunate 4mg/kg/day versus dihydroartemisinin-piperaquine once daily
Tijdsspanne: 03 days
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Patients who result as early treatment failures, late clinical failures, late parasitological failures or adequate clinical and parasitological response as indicators of efficacy
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03 days
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Recrudescence and new infection rate defined by polymerase chain reaction (PCR) analysis between treatment arms
Tijdsspanne: 42 days
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42 days
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Number of adverse events in each treatment arm
Tijdsspanne: After initiation and during follow-up treatment over a total follow-up period of 42 days.
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After initiation and during follow-up treatment over a total follow-up period of 42 days.
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Assess the pharmacokinetic characteristics of artesunate and dihydroartemisinin-piperaquine by using population pharmacokinetic modeling
Tijdsspanne: 03 days and upon relapse
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03 days and upon relapse
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Characterize different genetic patterns from different resistant strains
Tijdsspanne: 03 days
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03 days
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Medewerkers en onderzoekers
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Hien T Tran, MD, PhD, Oxford University Clinical Research Unit, Vietnam
Publicaties en nuttige links
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Studie record data
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Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
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Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Infecties
- Vector overgedragen ziekten
- Parasitaire ziekten
- Protozoaire infecties
- Malaria
- Anti-infectieuze middelen
- Antivirale middelen
- Antineoplastische middelen
- Antiprotozoaire middelen
- Antiparasitaire middelen
- Antimalariamiddelen
- Ontwormingsmiddelen
- Schistosomiciden
- Antiplatyhelmintische middelen
- Artesunaat
- Piperaquine
- Artenimol
Andere studie-ID-nummers
- 02MA
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