Study of Malaria Treatment at Phuoc Long Hospital, Binh Phuoc Province, Vietnam

NCT ID: NCT01165372

Last Updated: 2011-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-05-31

Brief Summary

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.

Detailed Description

This surveillance study is a three-arm prospective evaluation of the efficacy of artesunate and dihydroartemisinin-piperaquine in acute uncomplicated falciparum malaria. This will be an evaluation of the slope of the decline in the log parasitemia-time curve, parasite clearance times in patients randomized to one of two different doses of oral artesunate or dihydroartemisinin-piperaquine. People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with either artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily according to weight for 3 days. The artesunate arms will immediately follow with dihydroartemisinin-piperaquine therapy for 3 days (study days 3 - 6) at the dose defined by national guidelines. Patients on all three arms will be monitored for 42 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. PCR analysis will be used to distinguish between true recrudescence due to treatment failure and reinfection.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Artesunate or dihydroartemisinin-piperaquine

Intervention Type: DRUG

artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily

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.

Group Type: EXPERIMENTAL

Artesunate or dihydroartemisinin-piperaquine

Intervention Type: DRUG

artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily

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.

Group Type: EXPERIMENTAL

Artesunate or dihydroartemisinin-piperaquine

Intervention Type: DRUG

artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily

Interventions

Artesunate or dihydroartemisinin-piperaquine

artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

World Health Organization

OTHER

Sponsor Role: collaborator

Oxford University Clinical Research Unit, Vietnam

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hien T Tran, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oxford University Clinical Research Unit, Vietnam

Locations

Phuoc Long Hospital

Dong Xoai, Binh Phuoc, Vietnam

Countries

Vietnam

Related Links

http://www.oucru.org

Related Info

Other Identifiers

02MA

Identifier Type: -

Identifier Source: org_study_id