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

NCT02325180 | Completed Phase 4 DMC

• 1 other identifier: QA620
• Study Type: interventional
• Target: 338
• Locations: 1 country
• Sites: 3

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.

Conditions

Malaria, Falciparum

Keywords

ACT; Plasmodium falciparum; malaria; efficacy; Indonesia

Outcome Measures

Primary Outcomes (1)

• Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine

  Early treatment failure, late treatment failure, adequate clinical and parasitological response Proportion of participants with Adequate Clinical and Parasitological Response

  42 days

Secondary Outcomes (6)

• Parasite clearance times

  3 days

• Fever clearance times

  3 days

• Prevalence of molecular markers and the impact on treatment outcomes

  42 days

• Prevalence of gametocyte

  42 days

• Presence of other Plasmodium species

  42 days

Study Arms (2)

DHA-PQ

EXPERIMENTAL

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

AL

ACTIVE COMPARATOR

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

Interventions

Dihydroartemisinin-Piperaquine DRUG

Also known as: Duo-Cotecxin, Artekin

DHA-PQ

Artemether-lumefantrine DRUG

Also known as: Coartem

AL

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Universitas Sumatera Utara: collaborator

Study Sites (3)

Primary health centres

Kuala Langkat, North Sumatera, Indonesia

Location

Primary health centres

Tanjung Tiram, North Sumatera, Indonesia

Location

Pulau-pulau Batu health centres

Tello Island, North Sumatera, Indonesia

Location

Related Publications (8)

• Guidelines for the Treatment of Malaria. 2nd edition. Geneva: World Health Organization; 2010. Available from http://www.ncbi.nlm.nih.gov/books/NBK254223/

  PMID: 25473692 BACKGROUND

• White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet. 2014 Feb 22;383(9918):723-35. doi: 10.1016/S0140-6736(13)60024-0. Epub 2013 Aug 15.

  PMID: 23953767 BACKGROUND

• Fairhurst RM, Nayyar GML, Breman JG, Hallett R, Vennerstrom JL, Duong S, Ringwald P, Wellems TE, Plowe CV, Dondorp AM. Artemisinin-resistant malaria: research challenges, opportunities, and public health implications. Am J Trop Med Hyg. 2012 Aug;87(2):231-241. doi: 10.4269/ajtmh.2012.12-0025.

  PMID: 22855752 BACKGROUND

• Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM; Artemisinin Resistance in Cambodia 1 (ARC1) Study Consortium. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008 Dec 11;359(24):2619-20. doi: 10.1056/NEJMc0805011. Epub 2008 Dec 8. No abstract available.

  PMID: 19064625 BACKGROUND

• Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.

  PMID: 19641202 BACKGROUND

• White NJ. Malaria: a molecular marker of artemisinin resistance. Lancet. 2014 Apr 26;383(9927):1439-1440. doi: 10.1016/S0140-6736(14)60656-5. No abstract available.

  PMID: 24766952 BACKGROUND

• Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Menard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale JC, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Menard D. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014 Jan 2;505(7481):50-5. doi: 10.1038/nature12876. Epub 2013 Dec 18.

  PMID: 24352242 BACKGROUND

• Lubis IND, Wijaya H, Lubis M, Lubis CP, Beshir KB, Staedke SG, Sutherland CJ. Recurrence of Plasmodium malariae and P. falciparum Following Treatment of Uncomplicated Malaria in North Sumatera With Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine. Open Forum Infect Dis. 2020 Apr 2;7(5):ofaa116. doi: 10.1093/ofid/ofaa116. eCollection 2020 May.

  PMID: 32420402 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Colin J Sutherland, BSc PhD MPH

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: December 24, 2014
• Study Start: January 1, 2015
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: September 2, 2015

Record last verified: 2015-09

Locations

ID (3)