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

This study has been completed.
Sponsor:
Collaborator:
World Health Organization
Information provided by (Responsible Party):
Oxford University Clinical Research Unit, Vietnam
ClinicalTrials.gov Identifier:
NCT01165372
First received: July 15, 2010
Last updated: September 14, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: Artesunate or dihydroartemisinin-piperaquine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Investigation of In-vivo Susceptibility of P. Falciparum to Artesunate in Phuoc Long Hospital, Binh Phuoc Province, Vietnam

Resource links provided by NLM:


Further study details as provided by Oxford University Clinical Research Unit, Vietnam:

Primary Outcome Measures:
  • Slope of the decline in the log parasitemia-time curve relative to historical data [ Time Frame: 03 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clearance rate assessed from the fitted slope of the log-linear parasite curves [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Proportion of patients who have a parasite clearance time >72 hours after initiation of each treatment [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Parasitological efficacy of the three treatment arms [ Time Frame: Over 72 hours and during follow-up treatment over a total follow-up period of 42 days ] [ Designated as safety issue: No ]
  • Relative proportion of patients treated with artesunate 2mg/kg/day versus artesunate 4mg/kg/day versus dihydroartemisinin-piperaquine once daily [ Time Frame: 03 days ] [ Designated as safety issue: No ]
    Patients who result as early treatment failures, late clinical failures, late parasitological failures or adequate clinical and parasitological response as indicators of efficacy

  • Recrudescence and new infection rate defined by polymerase chain reaction (PCR) analysis between treatment arms [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Number of adverse events in each treatment arm [ Time Frame: After initiation and during follow-up treatment over a total follow-up period of 42 days. ] [ Designated as safety issue: Yes ]
  • Assess the pharmacokinetic characteristics of artesunate and dihydroartemisinin-piperaquine by using population pharmacokinetic modeling [ Time Frame: 03 days and upon relapse ] [ Designated as safety issue: No ]
  • Characterize different genetic patterns from different resistant strains [ Time Frame: 03 days ] [ Designated as safety issue: No ]

Enrollment: 166
Study Start Date: August 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Artesunate or dihydroartemisinin-piperaquine
artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily
Experimental: 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.
Drug: Artesunate or dihydroartemisinin-piperaquine
artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily
Experimental: 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.
Drug: Artesunate or dihydroartemisinin-piperaquine
artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily

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.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165372

Locations
Vietnam
Phuoc Long Hospital
Dong Xoai, Binh Phuoc, Vietnam, 84
Sponsors and Collaborators
Oxford University Clinical Research Unit, Vietnam
World Health Organization
Investigators
Principal Investigator: Hien T Tran, MD, PhD Oxford University Clinical Research Unit, Vietnam
  More Information

Additional Information:
No publications provided

Responsible Party: Oxford University Clinical Research Unit, Vietnam
ClinicalTrials.gov Identifier: NCT01165372     History of Changes
Other Study ID Numbers: 02MA
Study First Received: July 15, 2010
Last Updated: September 14, 2011
Health Authority: Viet Nam: Institute of Malaria, Parasitology and Entomology, Ho Chi Minh City

Keywords provided by Oxford University Clinical Research Unit, Vietnam:
Malaria
Drug resistance

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Artemisinins
Artesunate
Dihydroartemisinin
Piperaquine
Amebicides
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014