VHX: Study on the Treatment of Vivax Malaria

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT01074905

Collaborator

Mahidol University (Other)

655

Enrollment

Location

Arms

Duration (Months)

22.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Vivax Malaria	Drug: Artesunate Drug: Chloroquine Drug: Chloroquine/Primaquine	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

655 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

May 1, 2010

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

The first recurrence of Plasmodium vivax malaria [Day 28]
The first recurrence of Plasmodium vivax malaria within 28 days

Secondary Outcome Measures

Any recurrence of Plasmodium vivax parasitemia [1 year]
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 [1 year]
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% [1 year]
Overall number of days of illness and haematocrit below 30% within the follow up period
Chloroquine level [Day 7]
Whole blood chloroquine level at day 7 and any day of recurrence of Plasmodium vivax malaria
Adverse events [1 year]
Adverse event profiles of artesunate, chloroquine and primaquine

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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