AzTrials
AzTrials

FeverPhase 3NCT00393679

Evaluation of 4 Artemisinin-based Combinations for Treating Uncomplicated Malaria in African Children

A Phase 3 study testing amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ) and artemether-lumefantrine (AL) in people with Fever and Malaria, run by Institute of Tropical Medicine, Belgium at 8 sites in 7 countries.

Completed

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

Official record
Search all trials

Trial summary

The main objective is to compare the safety and efficacy of 4 artemisinin-based combinations (ACT) [amodiaquine-artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) and chlorproguanil/dapsone plus artesunate] for single and repeat treatments of uncomplicated malaria in children. Read more about this study

Who is it for?
Ages 6 to 59 months
Conditions the study is for
Fever, Malaria
What is being tested?
amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ) and artemether-lumefantrine (AL)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4,112 participants
Where
8 sitesin 7 countries
Study dates
Jul 2007to Dec 2009
Phase
Phase 3
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

  • Males and Females aged between 6 months and 59 months inclusive. In the sites where CDA is tested all recruited children will be aged between 12 months and 59 months inclusive (this arm was discontinued on 17th February 2008). This criterion applies only for the recruitment in the first follow up. For the second follow up, children having been included in the first follow up are eligible, regardless of their age.
  • Body weight of 5 Kg and above.
  • Microscopically confirmed, monoinfection of Plasmodium falciparum (parasitaemia ≥ 2,000/μL to 200,000/μL).
  • Fever (axillary temperature at ≥ 37.5°C) or history of fever in the previous 24 hours.
  • Haemoglobin value ≥ 7.0 g/dl;
  • Signed (or thumb-printed whenever parents/guardians are illiterate) informed consent by the parents or guardians. Note the informed consent will be asked only at recruitment and will cover the whole period of the study, including second active follow up and passive case detection.
  • Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the trial.

Who cannot join

  • Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.
  • Known hypersensitivity to the study drugs.
  • Severe malaria.
  • Danger signs: not able to drink or breast-feed, vomiting (> twice in 24hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand.
  • Presence of intercurrent illness or any condition (cardiac, renal, hepatic diseases) which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known G6PD deficiency.
  • Severe malnutrition (defined as weight for height <70% of the median NCHS/WHO reference).
  • Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocystis carinii pneumonia in children born to HIV+ women.

Trial locations and contacts

8 sites in 7 countries.

8 sites in 7 countries

Uganda2 sites
  • Jinja and Tororo

    Kampala

  • Mbarara,

    Mbarara

Other trials in Uganda

Burkina Faso1 site
  • Centre Muraz/IRSS

    Bobo-Dioulasso

Other trials in Burkina Faso

Gabon1 site
  • Albert Schweitzer Hospital

    Lambaréné

Other trials in Gabon

Mozambique1 site
  • Manhiça Health Research Center

    Manhiça

Other trials in Mozambique

Nigeria1 site
  • Hospital

    Calabar

Other trials in Nigeria

Rwanda1 site
  • Mashshesha and Rukara

    Kigali

Other trials in Rwanda

Zambia1 site
  • Tropical Diseases Research Centre, P O Box 71769,

    Ndola

Other trials in Zambia

About this study

The main objective is to compare the safety and efficacy of 4 artemisinin-based combinations (ACT) [amodiaquine-artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) and chlorproguanil/dapsone plus artesunate] for single and repeat treatments of uncomplicated malaria in children. Safety will be determined by registering adverse events and grading, laboratory, and vital signs evaluations. Their incidence will be compared between the different study arms.

TO BE NOTED: following GlaxoSmithKline decision to discontinue the clinical development of the fixed-doses combination of Lapdap (Chlorproguanil-Dapsone) and artesunate, the Lapdap plus Artesunate arm was immediately discontinued in this study, on 17th February 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities. The leading EC approved the amendment on 2nd June 2008.

TO BE NOTED: since the batches of the study drug DHAPQ expire at the end of October 2008, and because of the unavailability of a new batch of DHAPQ from the manufacturer, the recruitment in the DHAPQ arm had to be discontinued on 30th October 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.

Conditions
Fever, Malaria
Being tested
amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), Lapdap (Chlorproguanil-Dapsone) + artesunate (AS)
Keywords
Children 6-59 months, P.falciparum, Haemoglobin, Informed consent, ACT
Medical subject headings
Fever, Malaria

What participants receive

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

  • amodiaquine-artesunate (ASAQ)Drug

    Also called Coarsucam by Sanofi-Aventis

    A fix-dose combination tablet containing artesunate-amodiaquine in three different dosages, to be used according to patient age and weight: 25mg/67.5mg; 50mg/135mg; 100mg/270mg

  • dihydroartemisinin-piperaquine (DHAPQ)Drug

    Also called Artekin, Eurartekin by Sigma Tau, NOTE: batches expire on 31Oct08. Due to unavailability of new batches, recruitment in this arm was discontinued on 30Oct08.

    DHAPQ tablets contain either 20/160mg or 40/320mg of dihydroartemisinin (DHA) and piperaquine phosphate (PQ) respectively.

  • artemether-lumefantrine (AL)Drug

    Also called Coartem, Riamet by Novartis

    Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine.

  • Lapdap (Chlorproguanil-Dapsone) + artesunate (AS)Drug

    Also called Lapdap by GSK., Arsumax by Sanofi and Guilin.

    Lapdap tablets contain 15/18.75mg or 80/100mg of Chlorproguanil Hydrochloride and Dapsone, respectively. Arsumax® tablets contain 50mg Artesunate.

    TO BE NOTED: following GlaxoSmithKline decision to discontinue the clinical development of the fixed-doses combination of Lapdap (Chlorproguanil-Dapsone) and artesunate, the Lapdap plus Artesunate arm was immediately discontinued in this study, on 17th February 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.The leading EC approval was obtained on 2nd June 2008.

Study groups in NCT00393679
Study groupRoleWhat they receive
1ExperimentalAS-AQ
Receives: Drug: amodiaquine-artesunate (ASAQ)
2ExperimentalDHAPQ TO BE NOTED: since the batches of the study drug DHAPQ expire at the end of October 2008, and because of the unavailability of a new batch of DHAPQ from the manufacturer, the recruitment in the DHAPQ arm had to be discontinued on 30th October 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.
Receives: Drug: dihydroartemisinin-piperaquine (DHAPQ)
3ExperimentalAL
Receives: Drug: artemether-lumefantrine (AL)
4ExperimentalLapdap + AS TO BE NOTED: following GlaxoSmithKline decision to discontinue the clinical development of the fixed-doses combination of Lapdap (Chlorproguanil-Dapsone) and artesunate, the Lapdap plus Artesunate arm was immediately discontinued in this study, on 17th February 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.The leading EC approval was obtained on 2nd June 2008.
Receives: Drug: Lapdap (Chlorproguanil-Dapsone) + artesunate (AS)

What is being measured

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

  1. PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.

    Measured: Day 28

  2. PCR adjusted treatment failure up to day 28 (TF28A): all early failures before day 14 plus the recurrent parasitaemias detected at day 14 or later and classified by genotyping as recrudescence.

    Measured: Day 28

Secondary outcomes (11)
  1. PCR unadjusted treatment failure up to day 63 (TF63U): TF28U plus all cases of recurrent parasitaemia (symptomatic or asymptomatic) detected between day 29 and day 63 by passive follow up, regardless of genotyping

    Measured: Day 63

  2. PCR adjusted treatment failure for the whole period of passive surveillance (TFAPS): TF28A plus all episodes of recurrent parasitaemia identified as recrudescence by genotyping.

    Measured: Day 28

  3. Fever clearance time.

  4. Asexual parasite clearance time.

  5. Gametocytaemia (prevalence and density) at day 7, 14, 21 and 28 after treatment (for both active follow-ups);

    Measured: 28 days

  6. Hb changes day 3, 7, 14 and 28 (first and second follow up);

    Measured: 28 days

  7. Clinical malaria after first active follow-up;

    Measured: 28 Days

  8. Clinical malaria after second active follow-up;

    Measured: Up to seven months

  9. TF second clinical episode (D28 and D63);

    Measured: 63 days

  10. Changes in the frequency of mutations in the dihydrofolate reductase (DHFR) gene at day 0 first follow-up and day re-appearance of parasitaemia (for patients treated with CDA - NOTE that CDA arm was discontinued on 17.02.2008).

  11. Safety profiles including significant changes in relevant laboratory values.

    Measured: Up to seven months

Timeline

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

  1. First posted30 Oct 2006 (estimated)
  2. Study startJul 2007
  3. Primary completionDec 2009
  4. Study completionDec 2009

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4,112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00393679
Sponsor's protocol ID
4 ABC
Other IDs
IRB Antwerp: 6/40/187
Status last verified
Jan 2014
First submitted
27 Oct 2006
Last updated
3 Feb 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Ravinetto RM, Talisuna A, De Crop M, van Loen H, Menten J, Van Overmeir C, Tinto H, Gonzalez R, Meremikwu M, Nabasuma C, Ngoma GM, Karema C, Adoke Y, Chaponda M, Van Geertruyden JP, D'Alessandro U. Challenges of non-commercial multicentre North-South collaborative clinical trials. Trop Med Int Health. 2013 Feb;18(2):237-41. doi: 10.1111/tmi.12036. Epub 2012 Dec 10.

    PubMed 23217117
  • Four Artemisinin-Based Combinations (4ABC) Study Group. A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial. PLoS Med. 2011 Nov;8(11):e1001119. doi: 10.1371/journal.pmed.1001119. Epub 2011 Nov 8.

    PubMed 22087077

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ) and artemether-lumefantrine (AL) in people with Fever and Malaria, run by Institute of Tropical Medicine, Belgium at 8 sites in 7 countries.

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 7 inclusion and 7 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 3 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Uganda, Burkina Faso, Gabon, Mozambique, Nigeria and 2 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping. (time frame: Day 28). The study lists 2 primary outcomes in all. 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 NCT00393679, which also lists 2 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 3 Feb 2014.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in