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Malaria, FalciparumPhase 4NCT00374205

Randomized Trial on Effectiveness of ACTs in Ghana

A Phase 4 study testing Artesunate plus Amodiaquine and Artemether-Lumefantrine in people with Malaria, Falciparum, run by Bernhard Nocht Institute for Tropical Medicine at 1 site in Ghana.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to compare the effectiveness and safety of two Artemisinin Combination Therapies (ACTs) for the treatment of children with uncomplicated Plasmodium falciparum malaria Read more about this study

Who is it for?
Ages 6 to 59 months
Conditions the study is for
Malaria, Falciparum
What is being tested?
Artesunate plus Amodiaquine and Artemether-Lumefantrine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
245 participants
Where
1 siteGhana
Study dates
Sep 2006to Oct 2007
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 to 59 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Male and female outpatients aged 6 months to 59 months
  • Absence of severe malnutrition
  • A slide-confirmed P. falciparum asexual parasitaemia between 2,000/µl and 200,000/µl
  • A measured axillary temperature ≥ 37.5 °C or rectal/tympanic temperature ≥ 38.0 °C
  • Absence of general danger signs (unable to drink; repeated vomiting; recent history of convulsions; lethargic or unconscious state; unable to stand up or to sit)
  • Ability to tolerate oral therapy
  • Permanent residence in study area
  • Informed consent by the legal representative of the subject, if possible, the parents

Who cannot join

  • Adequate anti-malarial treatment within the previous 7 days
  • Antibiotic treatment for a current infection
  • Previous participation in a clinical trial
  • Haemoglobin < 5 g/dl
  • Leucocyte count: > 15000/µl
  • Mixed plasmodial infection
Show all 9Show fewer
  • Severe malaria as defined by WHO recommendations
  • Any other severe underlying disease (cardiac, renal, hepatic diseases, malnutrition, known HIV infection) or concomitant disease masking assessment of response
  • History of allergy or intolerance against trial medication

Trial locations and contacts

1 site in 1 country.

Ghana1 site

  • Agogo Presbyterian Hospital

    Agogo, Asante Akim North District

Other trials in Ghana

About this study

Official title: A Comparative Assessment of the Effectiveness of Artemether Plus Lumefantrine Versus Artesunate Plus Amodiaquine for the Treatment of Children With Uncomplicated Plasmodium Falciparum Malaria

The purpose of this study is to compare the effectiveness and safety of two Artemisinin Combination Therapies (ACTs) for the treatment of children with uncomplicated Plasmodium falciparum malaria

Read the detailed description

Childhood mortality related to Plasmodium falciparum malaria is on the rise with more than 1 million deaths per year in Sub-Saharan Africa. In the context of growing drug-resistance to antimalarials health officials are calling for rapid replacement of failing drugs by combining antimalarial drugs. Artemisinin Combination Antimalarial Therapies (ACTs) are in the focus of malaria control programmes and are recommended for first-line treatment in African countries. ACTs have been reported to be highly effective as artemisinin derivatives cause a rapid and substantial decrease in the parasite load when used for treating patients with malaria and resistance to artemisinin is still lacking. However, the short half-lives of artemisinins result in frequent recrudescent infections when used alone and therefore, much interest lays on the choice of the combination partner drug. ACTs also have been proposed as a means of reducing transmission by the reduction of gametocytes and of delaying the spread of drug resistance and prolonging the therapeutic life span of. Nevertheless, drug resistance of parasites to the respective partner drug is a matter of concern. Artesunate-amodiaquine (AQ) and artemether-lumefantrine (AL) are two registered fixed-dose artemisinin combination chemotherapies used in Africa which are GMP-manufactured at industrial scale. There is still limited data from randomised, controlled trials to support the general effectiveness of these two ACTs in Africa, including Ghana. More data is needed to compare these two therapies to make evidence-based first-line treatment decisions. Importantly, it is difficult to predict how combination therapy may affect the spread of drug resistance and monitoring drug resistance markers should be embedded in these trials to guide drug policy decision.

The aim of this open-labelled, randomised drug trial is to compare the effectiveness and safety of artesunate-amodiaquine (Arsucam®) against artemether plus lumefantrine (Coartem®) for the treatment of children under five years of age with uncomplicated Plasmodium falciparum malaria.

Being tested
Artesunate plus Amodiaquine, Artemether-Lumefantrine
Keywords
Ghana, Effectiveness, Safety, Drug-Resistance, ACT, Coartem, Arsucam
Medical subject headings
Malaria, Falciparum

What participants receive

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

  • Artesunate plus AmodiaquineDrug

    Also called Arsucam®

    Artesunate 50 mg and Amodiaquine 153 mg co-blister tablets: 3 days once daily weight-adjusted dosing according to manufacturer

  • Artemether-LumefantrineDrug

    Also called Coartem®

    Artemether 20 mg/Lumefantrine 120mg fixe-dose-combination tablets: 3 days twice daily weight-adjusted dosing according to manufacturer

Study groups in NCT00374205
Study groupRoleWhat they receive
ALExperimentalArtemether plus Lumefantrine 6 dose 3 days treatment
Receives: Drug: Artemether-Lumefantrine
ASAQActive comparatorArtesunate plus Amodiaquine
Receives: Drug: Artesunate plus Amodiaquine

What is being measured

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

  1. Clinical and PCR-controlled parasitological cure rate at day 28

    Measured: 28 days

Secondary outcomes (7)

  1. Clinical and PCR-controlled parasitological cure rate at day 14

    Measured: 14 days

  2. Effect on anaemia

    Measured: 28 days

  3. Molecular Drug Resistance Markers

    Measured: 28 days

  4. Recrudescence and Reinfection

    Measured: 28 days

  5. Effects on Gametocytemia

    Measured: 28 days

  6. Acceptance of Therapies

    Measured: 7 days

  7. Incidences of malaria episodes over a follow-up period of 1 year

    Measured: 12 months

Timeline

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

  1. First posted11 Sep 2006 (estimated)
  2. Study startSep 2006
  3. Study completionOct 2007

Why it stopped: Interim analysis showed more LCFs in one of the treatment arms

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
245 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00374205
Sponsor's protocol ID
01KA22062006
Status last verified
Nov 2007
First submitted
8 Sep 2006
Last updated
27 Nov 2007
Results posted
No
Data monitoring committee
Yes

Publications

  • Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, Rwakimari JB, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, Staedke SG. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin Trials. 2006 May;1(1):e7. doi: 10.1371/journal.pctr.0010007. Epub 2006 May 19.

    PubMed 16871329

  • Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, Greenwood BM, Whitty CJ. Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet. 2005 Apr 23-29;365(9469):1474-80. doi: 10.1016/S0140-6736(05)66417-3.

    PubMed 15850631

  • Makanga M, Premji Z, Falade C, Karbwang J, Mueller EA, Andriano K, Hunt P, De Palacios PI. Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data. Am J Trop Med Hyg. 2006 Jun;74(6):991-8.

    PubMed 16760509

  • Price RN, Uhlemann AC, van Vugt M, Brockman A, Hutagalung R, Nair S, Nash D, Singhasivanon P, Anderson TJ, Krishna S, White NJ, Nosten F. Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Clin Infect Dis. 2006 Jun 1;42(11):1570-7. doi: 10.1086/503423. Epub 2006 Apr 26.

    PubMed 16652314

  • Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Bjorkman A. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis. 2005 Oct 15;41(8):1079-86. doi: 10.1086/444460. Epub 2005 Sep 13.

    PubMed 16163624

  • Sidhu AB, Uhlemann AC, Valderramos SG, Valderramos JC, Krishna S, Fidock DA. Decreasing pfmdr1 copy number in plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. J Infect Dis. 2006 Aug 15;194(4):528-35. doi: 10.1086/507115. Epub 2006 Jul 11.

    PubMed 16845638

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Artesunate plus Amodiaquine and Artemether-Lumefantrine in people with Malaria, Falciparum, run by Bernhard Nocht Institute for Tropical Medicine at 1 site in Ghana.

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 8 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: stopped early, as of the sponsor's last update on 27 Nov 2007. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Ghana. 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 was stopped early (reason given: Interim analysis showed more LCFs in one of the treatment arms). Results are not available in the source record.

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?

Clinical and PCR-controlled parasitological cure rate at day 28 (time frame: 28 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 NCT00374205, which also lists 6 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 27 Nov 2007.

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