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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Mahidol University
Sponsor:
Information provided by (Responsible Party):
Mahidol University
ClinicalTrials.gov Identifier:
NCT01662700
First received: August 8, 2012
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Acute Uncomplicated Malaria With P.Vivax Infection
Drug: Artesunate
Drug: Chloroquine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Randomized Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand

Resource links provided by NLM:


Further study details as provided by Mahidol University:

Primary Outcome Measures:
  • Parasite Clearance Rate [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Incidence of relapse in P.vivax infection


Secondary Outcome Measures:
  • Parasite clearance time [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Parasite clearance time assessed by microscopy

  • Parasite density time [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Time of parasite count to fall to 50%, 90% and 99% of initial parasite density

  • Fever clearance time [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    IC0, IC90, IC99 of Plasmodium vivax responses to antimalarial drugs ( ex vivo)


Estimated Enrollment: 120
Study Start Date: October 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Drug: Chloroquine

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01662700

Locations
Thailand
Kraburi Hospital Recruiting
Ranong, Thailand
Contact: Thongchai Keeratihatayagorn, MD    +6681 8952244      
Contact: Prakaykaew Charunwatthana, MD    +6681-844 9678    jib@tropmedres.ac   
Sub-Investigator: Thongchai Keeratihatayagorn, MD         
Khunhan Hospital Recruiting
Srisaket, Thailand
Contact: Ratchadaporn Runchareon, MD    +6681-790-9275      
Contact: Prakaykaew Charunwatthana, MD    +6681-844 9678    jib@tropmedres.ac   
Sub-Investigator: Ratchadaporn Runchareon, MD         
Phusing Hospital Recruiting
Srisaket, Thailand
Contact: Kitipumi Chutasmit, MD    +6687 9654139      
Contact: Prakaykaew Charunwatthan, MD    +6681-844 9678    jib@tropmedres.ac   
Sub-Investigator: Kitipumi Chutasmit, MD         
Kap Choeng Hospital Recruiting
Surin, Thailand
Contact: Satawat Sinprasitkul, MD    +6681 7601087      
Contact: Prakaykaew Charunwatthana, MD    +6681-844 9678    jib@tropmedres.ac   
Sub-Investigator: Satawat Sinprasitkul, MD         
Sub-Investigator: Worawun Kopkitngam, MD         
Sponsors and Collaborators
Mahidol University
  More Information

No publications provided

Responsible Party: Mahidol University
ClinicalTrials.gov Identifier: NCT01662700     History of Changes
Other Study ID Numbers: FTM1202
Study First Received: August 8, 2012
Last Updated: January 24, 2013
Health Authority: Thailand: Ethical Committee

Keywords provided by Mahidol University:
P. vivax infection
Artesunate
Chloroquine
Primaquine

Additional relevant MeSH terms:
Infection
Malaria
Malaria, Vivax
Parasitic Diseases
Protozoan Infections
Antimalarials
Artesunate
Chloroquine
Chloroquine diphosphate
Amebicides
Analgesics
Analgesics, Non-Narcotic
Anthelmintics
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
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 30, 2014