Study on the Treatment of Vivax Malaria

Vivax Malaria Clinical Trial

— VHX  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01074905
• Other study ID #: SMRU0908
• Status: Completed
• Phase: Phase 3
• First received: February 23, 2010
• Last updated: August 27, 2013
• Start date: May 2010
• Est. completion date: October 2012

Study information

• Verified date: August 2013
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ethical Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 655
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Vivax
• Vivax Malaria

Intervention

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.
• Chloroquine
25 mg base/kg given in divided doses (10,10,5) over 3 days; Absolute range 20-30 mg/kg.
• Chloroquine/Primaquine
Chloroquine 3 days and Primaquine 14 days

Locations

Country	Name	City	State
Thailand	Shoklo Malaria Research Unit	Mae Sot

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	Mahidol University

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The first recurrence of Plasmodium vivax malaria	The first recurrence of Plasmodium vivax malaria within 28 days	Day 28	No
Secondary	Any recurrence of Plasmodium vivax parasitemia	Any recurrence of Plasmodium vivax parasitemia within the follow up period	1 year	No
Secondary	Time to first recurrence, median time between episodes of vivax infections and total number of episodes	Time to first recurrence, median time between episodes of vivax infections and total number of episodes in the follow up period	1 year	No
Secondary	Overall number of days of illness and haematocrit below 30%	Overall number of days of illness and haematocrit below 30% within the follow up period	1 year	No
Secondary	Chloroquine level	Whole blood chloroquine level at day 7 and any day of recurrence of Plasmodium vivax malaria	Day 7	No
Secondary	Adverse events	Adverse event profiles of artesunate, chloroquine and primaquine	1 year	Yes