Artemisinin-based Combination Therapy for Treatment of Plasmodium Falciparum Malaria in North Sumatera, Indonesia

September 1, 2015 updated by: London School of Hygiene and Tropical Medicine

Clinical Efficacy of Artemisinin-based Combination Therapy for Treatment of Uncomplicated Plasmodium Falciparum Malaria in North Sumatera, Indonesia and the Association of Molecular Markers With Treatment Outcomes

This is a prospective, open label, randomised controlled trial to assess the safety and efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria infection. Molecular markers for antimalarial resistance will also be assessed and the presence of molecular markers in the parasites will be associated with treatment outcomes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Artemisinin-based combination therapy (ACT) is the current recommended treatment by WHO for uncomplicated falciparum malaria. It is highly effective with few adverse effects. The artemisinin component is combined with a partner drug with a longer half-life to ensure the clearance of the remaining parasites after rapid reduction by artemisinin.

ACT is used as first-line treatment for uncomplicated P. falciparum infection in Indonesia since 2004. There are 3 combinations available in the country including artesunate-amodiaquine (AS-AQ), dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL). Studies at different sites across Indonesia have shown various efficacy. Yet, there is an increased concern of reduced susceptibility of P. falciparum to artemisinin in neighbouring countries. Therefore, there is a need to evaluate and monitor the efficacies of these combinations in Indonesia.

Molecular markers are an important tool for detecting and monitoring the presence of antimalarial resistance. Their significant implication is to geographically map the extent of resistant-parasites, thus enabling strategies for their control and elimination to be applied before the inevitably increase in the disease burden occurs. Different markers have been used to identify antimalarial resistance and recently a molecular marker for artemisinin susceptibility in P. falciparum has also been proposed. The presence of these markers in parasites from our study will also be investigated.

Study Type

Interventional

Enrollment (Actual)

338

Phase

  • 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 Locations

  • Indonesia
    • North Sumatera
      • Kuala Langkat, North Sumatera, Indonesia
        • Primary Health Centres
      • Tanjung Tiram, North Sumatera, Indonesia
        • Primary Health Centres
      • Tello island, North Sumatera, Indonesia
        • Pulau-pulau Batu health centres

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

Ages Eligible for Study

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

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female
  • All patients per 6 months of age
  • Fever as defined by axillary temperature > 37.5 C or history of fever during the 48 hours before recruitment
  • Infection with P. falciparum detected by microscopy
  • Parasitaemia > 250 /uL blood
  • Ability to swallow oral medication
  • Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule
  • Informed consent from the patient or from a parent or guardian in the case of children
  • Absence of history to hypersensitive reactions or contraindication to antimalarial drugs
  • Not currently consuming antibiotic with antimalarial activity (such as cotrimoxazole, macrolides, tetracycline or doxycycline)

Exclusion Criteria:

  • Presence of general danger signs in children under 5 years or signs of severe falciparum malaria according to the definitions of WHO (2000)
  • Presence of severe malnutrition according to WHO child growth standards
  • Presence of febrile conditions caused by diseases other than malaria
  • Presence of severe anemia (Hemoglobin < 7 gr/dL)
  • Received any of the study drugs within the past 4 weeks
  • Received any antimalarial within the last 2 weeks
  • Recurrent vomiting )necessitating more than a single repeat dose)
  • Pregnant (demonstrated by positive result of b-HCG in women of childbearing age
  • Lactating mother

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DHA-PQ
One tablet of dihydroartemisinin-piperaquine consists of 40 mg of dihydroartemisinin and 320 mg of piperaquine. DHA-PQ is administered once daily for 3 days (at enrolment, hour 24 and you 48). Dosing should be given based on body weight. Daily dose for dihydroartemisinin is 2.25 mg/kg (total 6.75 mg/kg) and for piperaquine is 18 mg/kg (total 54 mg/kg).
Drug: Dihydroartemisinin-Piperaquine
Other Names:
  • Artekin
  • Duo-Cotecxin
Active Comparator: AL
Half a tablet of artemether-lumefantrine consists of 20 mg of artemether and 120 mg of lumefantrine is given per 5 kg body weight. AL is administered as 6-dose regimens given twice daily for 3 days (at enrolment, hour 8, hour 24, hour 36, hour 48 and hour 60).
Drug: Artemether-lumefantrine
Other Names:
  • Coartem

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine
Time Frame: 42 days
Early treatment failure, late treatment failure, adequate clinical and parasitological response Proportion of participants with Adequate Clinical and Parasitological Response
42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Parasite clearance times
Time Frame: 3 days
Parasite reduction ratio, parasite clearance half-life
3 days
Fever clearance times
Time Frame: 3 days
3 days
Prevalence of molecular markers and the impact on treatment outcomes
Time Frame: 42 days
Pfcrt, Pfmdr1, Pfk13 and any other important molecular markers
42 days
Prevalence of gametocyte
Time Frame: 42 days
Proportion of patients with gametocyte
42 days
Presence of other Plasmodium species
Time Frame: 42 days
Plasmodium vivax, Plasmodium malariae, Plasmodium ovale spp, Plasmodium knowlesi
42 days
Haematological recovery
Time Frame: 28 days
Haemoglobin
28 days

Collaborators and Investigators

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

Sponsor

London School of Hygiene and Tropical Medicine

Collaborators

Universitas Sumatera Utara

Investigators

  • Principal Investigator: Colin J Sutherland, BSc PhD MPH, London School of Hygiene and Tropical Medicine

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

January 1, 2015

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

December 19, 2014

First Submitted That Met QC Criteria

December 19, 2014

First Posted (Estimate)

December 24, 2014

Study Record Updates

Last Update Posted (Estimate)

September 2, 2015

Last Update Submitted That Met QC Criteria

September 1, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QA620

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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