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Malaria, FalciparumPhase 4NCT02325180

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

A Phase 4 study testing Dihydroartemisinin-Piperaquine and Artemether-lumefantrine in people with Malaria, Falciparum, run by London School of Hygiene and Tropical Medicine at 3 sites in Indonesia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months and older
Conditions the study is for
Malaria, Falciparum
What is being tested?
Dihydroartemisinin-Piperaquine and Artemether-lumefantrine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
338 participants
Where
3 sitesIndonesia
Study dates
Jan 2015to Jun 2015
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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)

Who cannot join

  • 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
Show all 9Show fewer
  • Recurrent vomiting )necessitating more than a single repeat dose)
  • Pregnant (demonstrated by positive result of b-HCG in women of childbearing age
  • Lactating mother

Trial locations and contacts

3 sites in 1 country.

Indonesia3 sites

  • Primary health centres

    Kuala Langkat, North Sumatera

  • Primary health centres

    Tanjung Tiram, North Sumatera

  • Pulau-pulau Batu health centres

    Tello Island, North Sumatera

Other trials in Indonesia

About this study

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

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.

Read the 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.

Being tested
Dihydroartemisinin-Piperaquine, Artemether-lumefantrine
Keywords
ACT, Plasmodium falciparum, malaria, efficacy, Indonesia
Medical subject headings
Malaria, Falciparum, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dihydroartemisinin-PiperaquineDrug

    Also called Duo-Cotecxin, Artekin

  • Artemether-lumefantrineDrug

    Also called Coartem

Study groups in NCT02325180
Study groupRoleWhat they receive
DHA-PQExperimentalOne 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).
Receives: Drug: Dihydroartemisinin-Piperaquine
ALActive comparatorHalf 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).
Receives: Drug: Artemether-lumefantrine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 42 days

Secondary outcomes (6)

  1. Parasite clearance times

    Parasite reduction ratio, parasite clearance half-life

    Measured: 3 days

  2. Fever clearance times

    Measured: 3 days

  3. Prevalence of molecular markers and the impact on treatment outcomes

    Pfcrt, Pfmdr1, Pfk13 and any other important molecular markers

    Measured: 42 days

  4. Prevalence of gametocyte

    Proportion of patients with gametocyte

    Measured: 42 days

  5. Presence of other Plasmodium species

    Plasmodium vivax, Plasmodium malariae, Plasmodium ovale spp, Plasmodium knowlesi

    Measured: 42 days

  6. Haematological recovery

    Haemoglobin

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2014 (estimated)
  2. Study startJan 2015
  3. Primary completionJun 2015
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
338 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02325180
Sponsor's protocol ID
QA620
Status last verified
Sep 2015
First submitted
19 Dec 2014
Last updated
2 Sep 2015
Results posted
No
Data monitoring committee
Yes

Publications

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

    PubMed 25473692

  • 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.

    PubMed 23953767

  • 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.

    PubMed 22855752

  • 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.

    PubMed 19064625

  • 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.

    PubMed 19641202

  • 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.

    PubMed 24766952

  • 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.

    PubMed 24352242

  • 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.

    PubMed 32420402

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dihydroartemisinin-Piperaquine and Artemether-lumefantrine in people with Malaria, Falciparum, run by London School of Hygiene and Tropical Medicine at 3 sites in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine (time frame: 42 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02325180, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2015.

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