Study on the Treatment of Vivax Malaria (VHX)

This study has been completed.
Sponsor:
Collaborator:
Mahidol University
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01074905
First received: February 23, 2010
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

This is a randomised open label trial with follow up for 1 year. 660 adults and children above 6 months diagnosed with acute Plasmodium vivax will be randomised into 3 groups, either chloroquine, artesunate, or chloroquine/primaquine therapy. Participants will be screened on the day of inclusion then followed weekly for 8 visits and every 4 weeks until week 52. The primary objective of the study is to compare the efficacy of the WHO and Thai Ministry of Public Health recommended radical curative regimen of chloroquine and primaquine with the currently used monotherapy regimens of chloroquine and artesunate along the Thai-Burmese border.


Condition Intervention Phase
Vivax Malaria
Drug: Artesunate
Drug: Chloroquine
Drug: Chloroquine/Primaquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Open Label Study Comparing the Efficacy of Chloroquine/Primaquine, Chloroquine and Artesunate in the Treatment of Vivax Malaria Along the Thai-Burmese Border

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • The first recurrence of Plasmodium vivax malaria [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    The first recurrence of Plasmodium vivax malaria within 28 days


Secondary Outcome Measures:
  • Any recurrence of Plasmodium vivax parasitemia [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Any recurrence of Plasmodium vivax parasitemia within the follow up period

  • Time to first recurrence, median time between episodes of vivax infections and total number of episodes [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Time to first recurrence, median time between episodes of vivax infections and total number of episodes in the follow up period

  • Overall number of days of illness and haematocrit below 30% [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Overall number of days of illness and haematocrit below 30% within the follow up period

  • Chloroquine level [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
    Whole blood chloroquine level at day 7 and any day of recurrence of Plasmodium vivax malaria

  • Adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Adverse event profiles of artesunate, chloroquine and primaquine


Enrollment: 655
Study Start Date: May 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Artesunate
2 mg/kg/day as single daily dose given for 5 days; maximum dose range is 1.6 to 2.4 mg/kg/day or a total of 8 to 12 mg/kg.
Drug: Artesunate
2 mg/kg/day as single daily dose given for 5 days; maximum dose range is 1.6 to 2.4 mg/kg/day or a total of 8 to 12 mg/kg.
Active Comparator: Chloroquine
25 mg base/kg given in divided doses (10,10,5) over 3 days; Absolute range 20-30 mg/kg.
Drug: Chloroquine
25 mg base/kg given in divided doses (10,10,5) over 3 days; Absolute range 20-30 mg/kg.
Experimental: Chloroquine/Primaquine
Chloroquine 3 days and Primaquine 14 days
Drug: Chloroquine/Primaquine
Chloroquine 3 days and Primaquine 14 days

Detailed Description:

Considerably less attention has been paid to Plasmodium vivax epidemiology than Plasmodium falciparum. In areas of relatively low unstable transmission, which comprise the majority of P.vivax affected areas, vivax malaria is predominantly a disease of children (Luxemburger et al 1999). Chloroquine has long been the standard treatment for vivax malaria. Primaquine is recommended for radical cure of vivax malaria, but is difficult to administer due to dosing duration and side effects.

This study aims to characterize the epidemiologic history comparing the efficacy of 3 antimalarial regimens (chloroquine, artesunate, and chloroquine/primaquine) for plasmodium vivax in western Thailand. Chloroquine is currently the standard of treatment for Plasmodium vivax. Due to the long half-life or chloroquine, the first relapse of vivax malaria may be delayed. In contrast, artesunate has a very short half-life, thus, having no impact on first relapse. It is not known whether chloroquine reduces the overall number of relapses, or only delays the first relapse. There are many important questions about the biology of vivax malaria of relevance to treatment that remain unanswered. For example is the number of relapses per infection (i.e. per successful inoculation) predetermined or adaptive? If it is predetermined then suppression of the first relapse (as with chloroquine, mefloquine or piperaquine) will reduce the total number of relapses and this is a clear benefit. If it is adaptive then these drugs will simply delay the relapses and there is less clear benefit. These various uncertainties illustrate the importance of detailed comparative longitudinal evaluations. In order to characterize the biology of vivax malaria, it will be necessary to compare regimens with and without primaquine. Because of the challenges that face primaquine prescription (side effects, toxicity in G6PD deficient patients and duration of treatment), it is not commonly deployed along the Thai Burma border. In effect, we will be comparing usual practice (non primaquine regimens) with the recommended WHO and Thai MOPH practice (use of primaquine for 14 days). The information we will gather is crucial to the understanding of chloroquine and its effect on the vivax parasite. This will lead to future studies and invariably change the way we treat vivax malaria.

  Eligibility

Ages Eligible for Study:   6 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults and children > 6 months
  • Weight > 7 kg for children
  • Have not had primaquine since last Pv episode
  • Participant (or parent/guardian if < 18 years old) is willing and able to give written informed consent
  • Microscopic diagnosis of Plasmodium vivax mono-infection
  • Ability (in the investigators opinion) and willingness of patient or parent/guardian to comply with all study requirements

Exclusion Criteria

  • Allergy to artesunate, chloroquine or primaquine
  • Severe malaria
  • Patients with microscopic diagnosis of co-infection with Plasmodium falciparum
  • Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study
  • Inability to tolerate oral medication
  • Pregnancy
  • Blood transfusion in the last 3 months
  • Antimalarial in last 2 months
  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: NCT01074905

Locations
Thailand
Shoklo Malaria Research Unit
Mae Sot, Thailand
Sponsors and Collaborators
University of Oxford
Mahidol University
Investigators
Principal Investigator: Francois Nosten, MD Shoklo Malaria Research Unit
  More Information

No publications provided by University of Oxford

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01074905     History of Changes
Other Study ID Numbers: SMRU0908
Study First Received: February 23, 2010
Last Updated: August 27, 2013
Health Authority: Thailand: Ethical Committee

Keywords provided by University of Oxford:
vivax malaria
artesunate
chloroquine
primaquine
relapse

Additional relevant MeSH terms:
Malaria
Malaria, Vivax
Parasitic Diseases
Protozoan Infections
Artesunate
Chloroquine
Chloroquine diphosphate
Primaquine
Amebicides
Analgesics
Analgesics, Non-Narcotic
Anthelmintics
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimalarials
Antinematodal Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Central Nervous System Agents
Filaricides
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014