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

NCT ID: NCT01662700

Last Updated: 2013-01-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Acute Uncomplicated Malaria With P.Vivax Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Artesunate

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Chloroquine

Intervention Type: DRUG

Interventions

Artesunate

Intervention Type: DRUG

Chloroquine

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mahidol University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Khunhan Hospital

Si Sa Ket, Changwat Si Sa Ket, Thailand

Site Status: RECRUITING

Kraburi Hospital

Ranong, , Thailand

Site Status: RECRUITING

Phusing Hospital

Si Sa Ket, , Thailand

Site Status: RECRUITING

Kap Choeng Hospital

Surin, , Thailand

Site Status: RECRUITING

Countries

Thailand

Facility Contacts

Ratchadaporn Runchareon, MD

Role: primary

+6681-790-9275

Prakaykaew Charunwatthana, MD

Role: backup

jib@tropmedres.ac

+6681-844 9678

Thongchai Keeratihatayagorn, MD

Role: primary

+6681 8952244

Prakaykaew Charunwatthana, MD

Role: backup

jib@tropmedres.ac

+6681-844 9678

Kitipumi Chutasmit, MD

Role: primary

+6687 9654139

Prakaykaew Charunwatthan, MD

Role: backup

jib@tropmedres.ac

+6681-844 9678

Satawat Sinprasitkul, MD

Role: primary

+6681 7601087

Prakaykaew Charunwatthana, MD

Role: backup

jib@tropmedres.ac

+6681-844 9678

Other Identifiers

FTM1202

Identifier Type: -

Identifier Source: org_study_id