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

NCT01165372 | Completed Phase 2 DMC

• 1 other identifier: 02MA
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

Malaria; Drug resistance

Outcome Measures

Primary Outcomes (1)

• Slope of the decline in the log parasitemia-time curve relative to historical data

  03 days

Secondary Outcomes (8)

• Clearance rate assessed from the fitted slope of the log-linear parasite curves

  72 hours

• Proportion of patients who have a parasite clearance time >72 hours after initiation of each treatment

  72 hours

• Parasitological efficacy of the three treatment arms

  Over 72 hours and during follow-up treatment over a total follow-up period of 42 days

• Relative proportion of patients treated with artesunate 2mg/kg/day versus artesunate 4mg/kg/day versus dihydroartemisinin-piperaquine once daily

  03 days

• Recrudescence and new infection rate defined by polymerase chain reaction (PCR) analysis between treatment arms

  42 days

Study Arms (3)

Artesunate 2mg

EXPERIMENTAL

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.

Drug: Artesunate or dihydroartemisinin-piperaquine

Artesunate 4mg

EXPERIMENTAL

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.

Drug: Artesunate or dihydroartemisinin-piperaquine

DHA-piperaquine

EXPERIMENTAL

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.

Drug: Artesunate or dihydroartemisinin-piperaquine

Interventions

Artesunate or dihydroartemisinin-piperaquine DRUG

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

Artesunate 2mg; Artesunate 4mg; DHA-piperaquine

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oxford University Clinical Research Unit, Vietnam: lead
• World Health Organization: collaborator

Study Sites (1)

Phuoc Long Hospital

Dong Xoai, Binh Phuoc, 84, Vietnam

Location

Related Links

• Related Info

MeSH Terms

Conditions

Malaria

Interventions

Artesunate

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Hien T Tran, MD, PhD

  Oxford University Clinical Research Unit, Vietnam

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 19, 2010
• Study Start: August 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: September 15, 2011

Record last verified: 2011-09

Locations

VN (1)