Condition category
Infections and Infestations
Date applied
03/10/2008
Date assigned
09/10/2008
Last edited
31/03/2015
Prospective/Retrospective
Retrospectively 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

7071

Study information

Scientific title

A phase IV randomised study to assess the tolerability of artesunate-amodiaquine (AS-AQ) (Winthrop® fixed dose combination [FDC]) and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia

Acronym

Study hypothesis

1. To describe clinical tolerability of a fixed dose of AS-AQ (Winthrop® FDC) in adults and children over 6 years with uncomplicated Plasmodium falciparum malaria compared to a non-AQ containing reference therapy, i.e. artemether-lumefantrine
2. To describe serious adverse and drug related adverse events occurring within 1 month of drug administration for both treatments
3. To assess efficacy of treatment at 28 days
4. To describe day 0 and day 7 blood levels of desethyl-amodiaquine and lumefantrine
5. To promote awareness of drug safety issues and pharmacovigilance amongst health-care workers
6. To evaluate the ability of this method to detect serious adverse events and other safety information in the post-registration phase

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 31/05/2009.

Ethics approval

1. French CPP, approval on 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

Hospitals

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 (AS-AQ Winthrop®, Sanofi-Aventis): tablet strength AS/AQ 100/270 mg. Participants will be dosed according to body weight:
18 - 35.9 kg = 1 x 100/270 mg tablet once daily
Greater than 36 kg = 2 x 100/270 mg tablets once daily
2. Artemether-lumefantrine (Coartem, Novartis): tablet strength A/L 20/120 mg. Participants will be dosed according to body weight:
15 - 24.9 kg = 2 x 20/120 mg tablets twice daily, 8 - 12 hour between dosages
25 - 34.9 kg = 3 x 20/120 mg tablets twice daily, 8 - 12 hour between dosages
Greater than 35 kg = 4 x 20/120 mg tablets twice daily, 8 - 12 hour between dosages

For both arms: 3 days of treatment + 25 follow-up days (study duration/patient = 28 days).

Intervention type

Drug

Phase

Not Applicable

Drug names

Artesunate-amodiaquine (AS-AQ) (Winthrop® fixed dose combination [FDC]), artemether-lumefantrine

Primary outcome measures

To describe clinical tolerability of a fixed dose of AS-AQ (Winthrop® FDC) in adults and children over 6 years with uncomplicated P. falciparum malaria compared to a non-AQ containing reference therapy, i.e. artemether-lumefantrine. The clinical tolerability will be defined as the occurrence of most common adverse events.

Secondary outcome measures

1. To describe serious adverse and drug related adverse events occurring within 1 month of drug administration for both treatment
2. To assess efficacy of treatment at 28 days (polymerase chain reaction [PCR] genotyping corrected)
3. To describe day 0 and day 7 blood levels of desethyl-amodiaquine and lumefantrine

Overall trial start date

29/09/2008

Overall trial end date

01/04/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged greater than or equal to 6 years, either sex
2. Weight greater than or equal to 18 kg
3. Symptoms of malaria defined as fever (axillary temperature greater than or equal to 37.5°C), or history of fever in previous 48 hours
4. Microscopic confirmation of asexual stages of P. falciparum or mixed infection
5. Willingness to attend for follow-up
6. Signed informed consent by patient or responsible caregiver

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

1000 patients

Participant exclusion criteria

1. Pregnancy (pregnancy test to be performed in women of childbearing age)
2. Severe malaria
3. AS-AQ or AL treatment at appropriate dose or more than two doses of another antimalarial in the previous 4 weeks
4. Known hypersensitivity to artemisinin derivates or amodiaquine, or artemether-lumefantrine
5. Severe anaemia (less than 5 g/dl haemoglobin)
6. Concomitant febrile illness if additional medication is required other than antipyretics

Recruitment start date

29/09/2008

Recruitment end date

01/04/2009

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