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

Sponsor

London School of Hygiene and Tropical Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT02325180

Collaborator

Universitas Sumatera Utara (Other)

338

Enrollment

Locations

Arms

Duration (Months)

112.7

Patients Per Site

22.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria, Falciparum	Drug: Dihydroartemisinin-Piperaquine Drug: Artemether-lumefantrine	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

338 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

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: Duo-Cotecxin Artekin
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

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:

Duo-Cotecxin

Artekin

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

Outcome Measures

Primary Outcome Measures

Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine [42 days]
Early treatment failure, late treatment failure, adequate clinical and parasitological response Proportion of participants with Adequate Clinical and Parasitological Response

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country
1	Primary health centres	Kuala Langkat	North Sumatera	Indonesia
2	Primary health centres	Tanjung Tiram	North Sumatera	Indonesia
3	Pulau-pulau Batu health centres	Tello island	North Sumatera	Indonesia