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Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand

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ClinicalTrials.gov Identifier: NCT01662700
Recruitment Status : Unknown
Verified January 2013 by Mahidol University.
Recruitment status was:  Recruiting
First Posted : August 10, 2012
Last Update Posted : January 25, 2013
Sponsor:
Information provided by (Responsible Party):
Mahidol University

August 8, 2012
August 10, 2012
January 25, 2013
October 2012
December 2014   (Final data collection date for primary outcome measure)
  • Parasite Clearance Rate [ Time Frame: 7 days ]
    Parasite clearance rate as defined by the slope of the linear portion of the natural logarithm parasite clearance curve
  • Relapse rate of P. vivax [ Time Frame: 3 months ]
    Incidence of relapse in P.vivax infection
Same as current
Complete list of historical versions of study NCT01662700 on ClinicalTrials.gov Archive Site
  • Parasite clearance time [ Time Frame: 7 days ]
    Parasite clearance time assessed by microscopy
  • Parasite density time [ Time Frame: 7 days ]
    Time of parasite count to fall to 50%, 90% and 99% of initial parasite density
  • Fever clearance time [ Time Frame: 7 days ]
    Fever clearance time (i.e. the time taken for temperature to fall below 37 degrees celsius and remain there for at least 24 hrs)
  • Proportion of patients with gametocytemia [ Time Frame: 7 days ]
    Proportion of patients with gametocytemia before, during and after treatment, assessed at admission, on day 3 stratified by presence of gametocytes at enrolment
  • In vitro antimalarial drug susceptibility [ Time Frame: 7 days ]
    IC0, IC90, IC99 of Plasmodium vivax responses to antimalarial drugs ( ex vivo)
  • Parasite clearance time [ Time Frame: 7 days ]
    Parasite clearance time assessed by microscopy
  • Parasite density time [ Time Frame: 7 days ]
    Time of parasite count to fall to 50%, 90% and 99% of initial parasite density
  • Fever clearance time [ Time Frame: 7 days ]
    Fever clearance time (i.e. the time taken for temperature to fall below 37 degrees celcius and remain there for at least 24 hrs)
  • Proportion of patients with gametocytemia [ Time Frame: 7 days ]
    Proportion of patients with gametocytemia before, during and after treatment, assessed at admission, on day 3 stratified by presence of gametocytes at enrolment
  • In vitro antimalarial drug susceptibility [ Time Frame: 7 days ]
    IC0, IC90, IC99 of Plasmodium vivax responses to antimalarial drugs ( ex vivo)
Not Provided
Not Provided
 
Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand
An Open Label Randomized Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand

In Thailand, the proportion of P.vivax infection has now been increasing and is equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts.

Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as anti-relapse therapy. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported . The relapse rates at day 28 are about 50% without primaquine therapy and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days).

Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai-Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand.

The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.

Plasmodium vivax affects 70-80 million cases of malaria worldwide annually, is the major cause of human malaria in parts of Pacific region and South America. In Thailand, the proportion of P.vivax infection has increased and it is now equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts.

Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as antirelapse therapy. However, chloroquine-resistant P.vivax (CRPv) has been emer-ging in different parts of the world. The first report of chloroquine resistant Plasmodium vivax was in 2 Australian soldiers returning from Papua New Guinea in Indonesia and is now spreading over Asia and the Pacific region. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported. Occasional failure of the standard primaquine therapy (15 mg daily for 14 days) to prevent relapse has been observed. However, primaquine resistance has not been confirmed. In Thailand, the relapse rates at day 28 are about 50% without primaquine therapy, and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days).

A number of factors are reportedly associated with relapse, or the reappearance of P.vivax, including inadequate primaquine dosage, high parasitaemia at diagnosis, and short duration of symptoms prior to diagnosis, presence of gametocytes on admission, age, and gender. Because the radical cure of P.vivax hypnozoites requires 14 days of primaquine therapy, adherence to the drug regimen may greatly affect the prevention of relapse. Unfortunately, the effect of patient adherence on 14 day primaquine treatment, and its relation to preventing parasite reappearance, is not well-document.

Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai_Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand.

The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Acute Uncomplicated Malaria With P.Vivax Infection
  • Drug: Artesunate
  • Drug: Chloroquine
  • Experimental: AS2

    Artesunate 2 mg/kg/day for 5 days Combine with

    • Primaquine 15 mg is given daily for 14 days.
    • Or primaquine 45 mg is given once a week for 8 weeks in G6PD deficiency patients.
    Intervention: Drug: Artesunate
  • Active Comparator: Chloroquine

    CH25: Chloroquine 25 mg/kg: 15 mg base/kg on the first days (D0), followed by 5 mg base/kg daily on the second and third day (day1-2) (total 25 mg base/ kg).

    Combine with

    • Primaquine 15 mg is given daily for 14 days.
    • Or primaquine 45 mg is given once a week for 8 weeks in G6PD deficiency patients.
    Intervention: Drug: Chloroquine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Unknown status
120
Same as current
December 2014
December 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female, aged from 18 years to 65 years old who can come to the study hospital for follow up in case of re-infection
  • Acute uncomplicated malaria with P.vivax infection, confirmed by positive blood smear with asexual forms of P. vivax with parasitaemia > 1,000 parasites/microliters
  • Fever defined as temperature > 37.5 degree celsius or a history of fever within the last 24 hours
  • Written informed consent
  • Willingness and ability of the patients/guardians to comply with the study protocol for the duration of the study
  • Communicate with Thai language

Exclusion Criteria:

  • Mixed infection with other plasmodium species
  • For females: pregnancy, breast feeding
  • History of allergy or known contraindication to chloroquine, artesunate or primaquine
  • Any criteria of severe / complicated malaria (WHO 2010)
  • Presence of febrile condition caused by disease other than malaria.
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
 
NCT01662700
FTM1202
No
Not Provided
Not Provided
Mahidol University
Mahidol University
Not Provided
Not Provided
Mahidol University
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP