Condition category
Infections and Infestations
Date applied
03/10/2008
Date assigned
09/10/2008
Last edited
31/03/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Richard Smith

ORCID ID

Contact details

Saclepea CHC
Nimba county
-
Liberia

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

7070

Study information

Scientific title

Efficacy of amodiaquine-artesunate and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Nimba county, Liberia

Acronym

Study hypothesis

1. To evaluate the efficacy of amodiaquine-artesunate and artemether-lumefantrine among children between 6 and 59 months old suffering from uncomplicated malaria defined as the polymerase chain reaction (PCR)-adjusted cure rates at day 42
2. To assess the safety of amodiaquine-artesunate and artemether-lumefantrine treatment among children between 6 and 59 months old suffering from uncomplicated malaria
3. To assess inter-patient absorption differences possibly influencing efficacy
4. To formulate recommendations for adapted case management in Nimba county

As of 13/05/2010, this record was updated to include the actual last patient visit date; the overall trial end date at the time of registration was 30/04/2009.

Ethics approval

1. French CPP, 03/07/2008
2. Liberian Ministry of Health and Social Welfare, approval on 23/09/2008

Study design

Randomised single-blind two-armed single-centre comparative study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Malaria

Intervention

Patients will be equally randomised into the following treatment groups:
1. Artesunate-amodiaquine fixed dose combination (AS/AQ FDC) (artesunate amodiaquine Winthrop® Sanofi Aventis):
1.1. Artesunate 25 mg/amodiaquine 67.5 mg 1 tablet/day for 3 days in children 5 kg to 8.9 kg
1.2. Artesunate 50 mg/amodiaquine 135 mg 1 tablet/day for 3 days in children 9 kg to 17.9 kg
1.3. Artesunate 100 mg/amodiaquine 270 mg 1 tablet/day for 3 days in children 18 kg to 35.9 kg
2. Coartem®: artemether 20 mg - lumefantrine 120 mg co-formulated tabs (Coartem®, Novartis) given as six twice-daily doses over three days:
2.1. One tablet/dose for weight 5 - 14.9 kg (total 6 tablets)
2.2. Two tablets/dose for weight 15 - 24.9 kg (total 12 tablets)
2.3. Three tablets/dose for weight 25 - 34.9 kg (total 18 tablets)
2.4. Four tablets/dose for weight greater than or equal to 35 kg (total 24 tablets)
The second dose will be given 8 to 12 hours after the first dose, given at inclusion. Patients will be given milk, or encouraged to breastfeed, before each dose is taken.

For both arms: 3 days of treatment + 39 follow-up days (study duration/patient = 42 days).

Intervention type

Drug

Phase

Not Applicable

Drug names

Amodiaquine-artesunate, artemether-lumefantrine

Primary outcome measures

1. To evaluate the efficacy of both drugs uncorrected by PCR genotyping at day 42 and to compare the re-infection rates
2. To evaluate the PCR corrected and uncorrected efficacy of amodiaquine-artesunate and artemether-lumefantrine on day 28 of follow up

Secondary outcome measures

1. To assess the safety of amodiaquine-artesunate and artemether-lumefantrine treatment among children between 6 and 59 months old suffering from uncomplicated malaria by documenting adverse events that occurred during the study, before:
1.1. Day 28
1.2. Day 42
1.3. By documenting serious adverse events (SAE)
2. To assess inter patient absorption differences possibly influencing efficacy by measuring the pharmacokinetic (PK) of amodiaquine and lumefantrine at day 0 and day 7

Overall trial start date

17/11/2008

Overall trial end date

01/07/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age group of 6 and 59 months, either sex
2. Weight greater than or equal to 5 kg
3. Slide-confirmed infection with Plasmodium falciparum only (no mixed infections)
4. Asexual parasite density between 2,000 and 200,000/µl of blood, and
5. Measured axillary temperature greater than or equal to 37.5°C or history of fever in the last 48 hours, and
6. High probability of respecting the follow-up visits (residence within 1 hour walking distance from the OPD, no upcoming travel plans, etc.), and
7. Informed consent from a parent or guardian aged at least 18 years

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

300

Participant exclusion criteria

1. General danger signs according to the World Health Organization (WHO) definition, or
2. Signs of severe/complicated malaria according to the WHO definition, or
3. Severe anaemia (haemoglobin less than 5 g/dL), or
4. Known history of hypersensitivity to any of the study drugs, or
5. Severe malnutrition (as defined by a weight-for-height below 70% of median and/or symmetrical oedemas involving at least the feet), or
6. Concomitant febrile illness judged as due to causes other than malaria with the potential to confound study outcome (measles, acute lower tract respiratory infection, otitis media, tonsillitis, abscesses, severe diarrhoea with dehydration, etc.; mild flu shouldn't lead to exclusion)
7. Having received already a full course of the treatment (or one of the treatments) under study in the previous 10 days

Recruitment start date

17/11/2008

Recruitment end date

01/07/2009

Locations

Countries of recruitment

Liberia

Trial participating centre

Saclepea CHC
Nimba county
-
Liberia

Sponsor information

Organisation

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Sponsor details

15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland

Sponsor type

Research organisation

Website

http://www.dndi.org/

Funders

Funder type

Research organisation

Funder name

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23866774
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23866736

Publication citations

  1. Results

    Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, Pinoges L, Dhorda M, Boum Y, Sundaygar T, Zolia YM, Jones JJ, Comte E, Houzé P, Jullien V, Carn G, Kiechel JR, Ashley EA, Guérin PJ, Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial., Malar. J., 2013, 12, 251, doi: 10.1186/1475-2875-12-251.

  2. Results

    Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, Pinoges L, Sundaygar T, Zolia YM, Jones JJ, Comte E, Bruneel A, Branger M, Jullien V, Carn G, Kiechel JR, Ashley EA, Guérin PJ, Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia, Malar J, 2013 , 12, 250, doi: 10.1186/1475-2875-12-250.

Additional files

Editorial Notes