Artemisinin-Based Combination Therapy: Clinical Trials in Cameroon - Full Text View

Sponsors and Collaborators:	Gates Malaria Partnership University of Yaounde Health Board, Cameroon Baptist Convention, Cameroon
Information provided by:	Gates Malaria Partnership
ClinicalTrials.gov Identifier:	NCT00297882

Purpose

This proposal aims to evaluate the safety and efficacy of artemisinin-based anti-malaria combination drugs (ACTs)for treatment of children aged 1-10 years in different locations in Cameroon. Randomized clinical trials will provide local data on the safety of the test drugs, and on putative marker mutations of the development of resistance to ACT. The study will involve three centres, namely, Banso (Guinea-Savannah region), Limbe(Littoral Forest), and Garoua(Sahel-Savannah). The trial will compare the efficacy and safety of Amodiaquine(AQ)-Artesunate(Art) with Coartem®(Artemether-Lumefantrine). Drug efficacy will be determined using a WHO standardised 28 day protocol. Safety will be monitored through clinical examination, and biochemical and haematological indices. Molecular markers of artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles of the PfATP6 gene in drug failure cases, . Recrudescences or re-infections will be assessed by analysis of the msp1 and msp2 genes. The impact of these combinations on generation of gametocytes will be determined from gametocyte carriage rates measured by microscopy.

Condition	Intervention	Phase
Malaria	Drug: Artemether-Lumefantrine , Amodiaquine-Artesunate	Phase III

MedlinePlus related topics: Malaria

Drug Information available for: Artesunate Artemisinin Artemether Benflumetol Amodiaquine Amodiaquine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase III Clinical Trials of Artemisinin-Based Combination Therapy in Cameroon

Further study details as provided by Gates Malaria Partnership:

Primary Outcome Measures:

Cure rate on Day 28 [ Time Frame: Day 1, 2, 3, 7, 14, 28 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Cure rate on Day 14 [ Time Frame: Day 1, 2, 3, 7, 14 ] [ Designated as safety issue: Yes ]
Adverse Events by Day 28 [ Time Frame: Day 1, 2, 3, 7, 14, 28 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	305
Study Start Date:	July 2006
Estimated Study Completion Date:	July 2008
Estimated Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 Artemether-Lumefantrine: Active Comparator	Drug: Artemether-Lumefantrine , Amodiaquine-Artesunate Artemether-Lumefantrine(Co-Artem)=Artemether, 2mg/kg x 2(12h apart) and Lumefantrine, 12mg/kgx2 (12h apart). Amodiaquine-ArtemetherD0(0H),D1(24H),D2(48H)- Artesunate 4mg/kg and Amodiaquine at 10mg/kg
2 Amodiaquine-Artemether: Active Comparator	Drug: Artemether-Lumefantrine , Amodiaquine-Artesunate Artemether-Lumefantrine(Co-Artem)=Artemether, 2mg/kg x 2(12h apart) and Lumefantrine, 12mg/kgx2 (12h apart). Amodiaquine-ArtemetherD0(0H),D1(24H),D2(48H)- Artesunate 4mg/kg and Amodiaquine at 10mg/kg

Detailed Description:

Out patients will be screened for malaria by blood film examination
Malaria-positive children will be examined by the physician for inclusion or exclusion(see below)
Informed consent will be sought from guardians of potential patients
Patients or guardians will be interviewed and a case record form completed
Patients will be randomised into one of the two arms in the ratio 4:1 AQ/Art: CoArtem and issued a study card
Filter paper and 5ml venous blood samples will be collected
Patients will be hospitalised for three days to allow completion of therapy under observation
The patient will be asked to return on days 7, 14 and 28 for assessment of clearance or recrudescence of parasites
Patient will be examined for parasites and evaluated for early treatment failure (ETF), late treatment failure (LTF), late parasitological failure (LPF) or adequate clinical and parasitological response.(ACPR).
If a patient does not appear for follow up, a community health worker will try to trace them and will collect blood onto filter paper and a microscope slide should the patient have a temperature ≥ 37.5°C
Patients whose parents opt out of the study will be administered quinine sulphate if parasitaemic
Filter paper samples will be air dried and stored with dessicant until required.
Whole blood samples collected into citrate as anticoagulant will be processed for plasma, aliquoted into 300µl lots and stored at -70°C.
Patient information will be entered at the close of each day into laptops and collectively sent to Yaounde at the end of the first month of study and thereafter at the end of each week, along with the hard copies of the case report forms.
Analysis will be performed on the samples within three months of collection for molecular markers of resistance, genetic structure of parasites and for blood drug levels of medications used in the trial

Eligibility

Ages Eligible for Study:	12 Months to 120 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

children aged 1-10 years;
axillary temperature ≥ 37.5°C and/or history of fever within past 24 hours;
P. falciparum asexual parasitaemia between 1000 and 100000/µl;
ability to attend follow-up visits.

Exclusion criteria:

co-infections;
underlying chronic disease;
severe malaria as indicated by hyperparasitaemia, severe anaemia(PCV 15%, Hb 5g/ml), respiratory distress, inability to drink, persistent vomiting in past 24 hours;
recent history of multiple convulsions;
jaundice;
inability to stand or sit;
history of allergy to study drug.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00297882

Contacts

Contact: Wilfred F Mbacham, ScD	237-757 9180	wfmbacham@yahoo.com
Contact: Rose Leke, PhD	237-223 7429	rose.leke@yahoo.com

Locations

Cameroon, Centre
Biotechnology Centre	Recruiting
Yaounde, Centre, Cameroon
Contact: Wilfred F Mbacham, ScD 237-757 9180 wfmbacham@yahoo.com
Contact: Rose Leke, PhD 237-223 7429 rose.leke@yahoo.com
Principal Investigator: Wilfred Mbacham, ScD

Sponsors and Collaborators

Gates Malaria Partnership

University of Yaounde

Health Board, Cameroon Baptist Convention, Cameroon

Investigators

Principal Investigator:

Wilfred F Mbacham, ScD

University of Yaounde

More Information

(Gates Malaria Partnership) This link exits the ClinicalTrials.gov site

Responsible Party:	Biotechnology Centre, University of Yaounde I, Cameroon ( Dr W Mbacham )
Study ID Numbers:	ITCRVG46
Study First Received:	February 28, 2006
Last Updated:	March 12, 2008
ClinicalTrials.gov Identifier:	NCT00297882
Health Authority:	Cameroon: Ministry of Public Health

Keywords provided by Gates Malaria Partnership:

Efficacy
Safety
Children
Cameroon

Study placed in the following topic categories:

Benflumetol
Artesunate
Artemether-lumefantrine combination
Amodiaquine
Artemisinins
Clotrimazole

Miconazole
Artemisinine
Tioconazole
Malaria
Artemether

Additional relevant MeSH terms:

Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Antiplatyhelmintic Agents
Antifungal Agents

Therapeutic Uses
Anthelmintics
Amebicides
Coccidiostats
Schistosomicides
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009