Effectiveness of Artemisinin Combination Regimens in Falciparum Malaria (ACT)

May 14, 2009 updated by: Medecins Sans Frontieres, Netherlands

Comparing the Effectiveness of 5 Artemisinin Combination Treatment Regimens in the Treatment of Uncomplicated Falciparum Malaria

Antimalarial drug resistance is increasing nearly everywhere in the tropical world, confounding global attempts to "Roll Back Malaria." South East Asia has the most resistant malaria parasites in the world. This has limited the options for treatment in this region.

Artemisinin-based combination therapy is now the recommended treatment for uncomplicated falciparum malaria. The success of this policy change in practice will depend on the efficacy of the components of the combination used, the population coverage achieved, high levels of adherence to treatment, low cost of the drugs, and preferably the drugs in a combination treatment should be formulated in a single tablet, to prevent one drug being taken without the partner drug. Until recently there were only two artemisinin-based fixed combinations available, artemether-lumefantrine and dihydroartemisinin-piperaquine; and only the former has international registration. More fixed combinations are needed urgently.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Malaria in Myanmar:

In Myanmar, malaria is the number one cause of morbidity. According to the Department of Health (DoH) and WHO there are approximately 500,000 patients with malaria each year. About 80% of reported infections are due to Plasmodium falciparum and 20% are due to Plasmodium vivax. This is likely to be a severe underestimation. MSF-Holland alone treats already 250,000 slide positive malaria patients per year in an area of mixed endemicity covering a population of less that 1 million patients out of a total population of 54 million in the country.

Chloroquine was the first line treatment for falciparum malaria for the last five decades. In 1996 and 1998 MSF-Holland with support from the Wellcome Trust (Prof N. White) performed studies in the northern and western part of the country, in which very high in-vivo resistance levels to chloroquine and sulfadoxine-pyrimethamine were demonstrated1,2. Combination treatment of mefloquine plus artesunate (loose tablets) [MA(LT)]and treatment with dihydroartemisinin-piperaquine (DP) both proved highly efficacious (99-100%)3,4. The studies performed by MSF provided an important component of the evidence used to convince the health authorities that a change of national protocol was needed. In 2001, the DOH of Myanmar changed the national protocol for the treatment of uncomplicated falciparum malaria; a 3 day treatment of mefloquine-artesunate was chosen to become the first line treatment. Artemether-lumefantrine (AL) and DP are also mentioned in the national protocol as effective treatment regimens, but there is a call in the protocol for more research of these treatments.

These changes in policy are a very good step forward and were widely respected. In practice, some problems remain.

MSF has implemented large malaria activities in Myanmar over the past decade. The programme has performed a diagnostic test for malaria for approximately 3,000,000 patients and approximately 1,500,000 patients have been treated with artemisinin combination treatment (ACT).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
600

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Myanmar
      • Kachin, Myanmar
        • Recruiting
        • Myit Kyi Nar Clinic
        • Contact:
        • Principal Investigator:
          • Mya Nee Nyo, MD
      • Maungdaw, Myanmar
        • Recruiting
        • Myothugyi Rural Health Center, Bu Thee Daung
        • Contact:
        • Principal Investigator:
          • Arkar Linn Naing, MD
      • Shan, Myanmar
        • Recruiting
        • Lashio Clinic
        • Contact:
          • Naing Nyo, MD
        • Principal Investigator:
          • Naing Zaw, MD
    • Rakhine
      • Sittwe, Rakhine, Myanmar
        • Recruiting
        • Dabhine and Mingan Clinic
        • Contact:
        • Principal Investigator:
          • Pyay Phyo Aung, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  • Age over 6 months and
  • Weight ≥ 5 kg, and
  • Slide-confirmed infection with Plasmodium falciparum (including mixed infections), and
  • Asexual parasite density between 500 and 200,000/µl of blood, and
  • Informed consent from a parent or guardian aged at least 18 years.

Exclusion criteria

  • General danger signs according to the WHO definition or
  • Signs of severe/complicated malaria according to the WHO definition or
  • Severe anaemia (haemoglobin < 5 g/dL), or
  • Known history of hypersensitivity to any of the study drugs, or
  • Severe malnutrition (as defined by a weight-for-height below 70% of median and/or symmetrical oedemas involving at least the feet), or
  • Concomitant febrile illness due to causes other than malaria with the potential to confound study outcome (measles, acute lower tract respiratory infection, otitis media, tonsillitis, abscesses, severe diarrhoea with dehydration, etc.; mild flu should not lead to exclusion) or
  • History of psychiatric diseases, or
  • Having received a full course treatment including MQ in the preceding 9 weeks or
  • Having received any other antimalarials in the previous 48 hours.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: AM(LT)
Artesunate (Arsumax®, Sanofi)
Drug: AM(LT)
Artesunate (Arsumax®, Sanofi) 50 mg tabs given at 4 mg/Kg/day on day 0, day 1 and day 2 (total 12 mg/Kg) PLUS Mefloquine 250 mg base tabs given at 25 mg/Kg on day 0. Treatment is given in three equally divided daily doses to the nearest quarter tablet.
Other Names:
  • Lariam®, Roche
Experimental: AM(FDC)
Artesunate-mefloquine fixed dose combination
Drug: AM(FDC)
Artesunate-mefloquine fixed dose combination (artesunate 25mg/mefloquine hydrochloride 55mg, or artesunate 100mg/mefloquine hydrochloride 220mg), according to age-group.
Other Names:
  • Far-Manguinhos, Brazil
Experimental: AL
artemether 20 mg - lumefantrine 120 mg co-formulated tabs
Drug: AL
Coartem®: artemether 20 mg - lumefantrine 120 mg co-formulated tabs (Coartem®, Novartis) given as six twice-daily doses over three days, according to weight-groups. The second dose should be taken 6 to 10 hours after the first dose, given at inclusion. Patients will be advised to take some fatty food (or encouraged to give breast feeding) before each dose is taken. Fatty food or milk will not be provided by the researchers.
Other Names:
  • Coartem®
Experimental: DP
40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/Piperaquine 160 mg tablets
Drug: DP
40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/ Piperaquine 160 mg tablets),. Treatment is given according to age groups. In the age group <6yrs of age, a subdivision according to weight is made
Other Names:
  • DuoCotecxin, Holley Pharm
Experimental: AA (FDC)
Artesunate-amodiaquine fixed dose combination
Drug: AA(FDC)
Artesunate-amodiaquine fixed dose combination (FDC) (Artesunate Amodiaquine Winthrop® Sanofi Aventis); Artesunate 25mg/amodiaquine 67.5mg; Artesunate 50mg/amodiaquine 135mg ; Artesunate 100mg/amodiaquine 270mg
Other Names:
  • Artesunate Amodiaquine Winthrop® Sanofi Aventis

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Cure rate
Time Frame: 63 days
63 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Early treatment failure
Time Frame: Day 6
Day 6
Late treatment failure
Time Frame: Day 63
Day 63
Adequate response
Time Frame: Day 63
Day 63

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medecins Sans Frontieres, Netherlands

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Oxford
Mahidol University
Disease Control, Department of Health, Myanmar

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Frank Smithuis, MD, Medecins Sans Frontieres, Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2008

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2009

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 30, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 15, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 15, 2009

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2009

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • YNG0901

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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