Artemisinin-Based Combination Therapy: Clinical Trials in Cameroon

This study has been completed.
Sponsor:
Collaborators:
University of Yaounde
Health Board, Cameroon Baptist Convention, Cameroon
Information provided by (Responsible Party):
Dr Wilfred Mbacham, Gates Malaria Partnership
ClinicalTrials.gov Identifier:
NCT00297882
First received: February 28, 2006
Last updated: April 28, 2013
Last verified: April 2013
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Phase III Clinical Trials of Artemisinin-based Combination Therapy in Cameroon

Resource links provided by NLM:


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 ]

Enrollment: 900
Study Start Date: July 2006
Study Completion Date: July 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Artemether-Lumefantrine Drug: Artemether-Lumefantrine , Amodiaquine-Artesunate
  1. Artemether-Lumefantrine(Co-Artem)=Artemether, 2mg/kg x 2(12h apart) and Lumefantrine, 12mg/kgx2 (12h apart).
  2. Amodiaquine-ArtemetherD0(0H),D1(24H),D2(48H)- Artesunate 4mg/kg and Amodiaquine at 10mg/kg
Other Name: CoArtem, Arsucam
Active Comparator: 2 Amodiaquine-Artemether Drug: Artemether-Lumefantrine , Amodiaquine-Artesunate
  1. Artemether-Lumefantrine(Co-Artem)=Artemether, 2mg/kg x 2(12h apart) and Lumefantrine, 12mg/kgx2 (12h apart).
  2. Amodiaquine-ArtemetherD0(0H),D1(24H),D2(48H)- Artesunate 4mg/kg and Amodiaquine at 10mg/kg
Other Name: CoArtem, Arsucam

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

No publications provided

Responsible Party: Dr Wilfred Mbacham, PI, Gates Malaria Partnership
ClinicalTrials.gov Identifier: NCT00297882     History of Changes
Other Study ID Numbers: ITCRVG46
Study First Received: February 28, 2006
Last Updated: April 28, 2013
Health Authority: Cameroon: Ministry of Public Health

Keywords provided by Gates Malaria Partnership:
Efficacy
Safety
Children
Cameroon

Additional relevant MeSH terms:
Lumefantrine
Artemether
Artesunate
Amodiaquine
Artemether-lumefantrine combination
Artemisinins
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Amebicides

ClinicalTrials.gov processed this record on October 19, 2014