Randomized Trial on Effectiveness of ACTs in Ghana

This study has been terminated.
(Interim analysis showed more LCFs in one of the treatment arms)
Sponsor:
Collaborators:
Presbyterian Health Service (PHS)
Kumasi Centre for Collaborative Research (KCCR)
School of Medical Sciences Kumasi (SMS/KNUST)
Information provided by:
Bernhard Nocht Institute for Tropical Medicine
ClinicalTrials.gov Identifier:
NCT00374205
First received: September 8, 2006
Last updated: November 26, 2007
Last verified: November 2007
  Purpose

The purpose of this study is to compare the effectiveness and safety of two Artemisinin Combination Therapies (ACTs) for the treatment of children with uncomplicated Plasmodium falciparum malaria


Condition Intervention Phase
Malaria, Falciparum
Drug: Artesunate plus Amodiaquine
Drug: Artemether-Lumefantrine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Comparative Assessment of the Effectiveness of Artemether Plus Lumefantrine Versus Artesunate Plus Amodiaquine for the Treatment of Children With Uncomplicated Plasmodium Falciparum Malaria

Resource links provided by NLM:


Further study details as provided by Bernhard Nocht Institute for Tropical Medicine:

Primary Outcome Measures:
  • Clinical and PCR-controlled parasitological cure rate at day 28 [ Time Frame: 28 days ]

Secondary Outcome Measures:
  • Clinical and PCR-controlled parasitological cure rate at day 14 [ Time Frame: 14 days ]
  • Effect on anaemia [ Time Frame: 28 days ]
  • Molecular Drug Resistance Markers [ Time Frame: 28 days ]
  • Recrudescence and Reinfection [ Time Frame: 28 days ]
  • Effects on Gametocytemia [ Time Frame: 28 days ]
  • Acceptance of Therapies [ Time Frame: 7 days ]
  • Incidences of malaria episodes over a follow-up period of 1 year [ Time Frame: 12 months ]

Enrollment: 245
Study Start Date: September 2006
Study Completion Date: October 2007
Arms Assigned Interventions
Experimental: AL
Artemether plus Lumefantrine 6 dose 3 days treatment
Drug: Artemether-Lumefantrine
Artemether 20 mg/Lumefantrine 120mg fixe-dose-combination tablets: 3 days twice daily weight-adjusted dosing according to manufacturer
Other Name: Coartem®
Active Comparator: ASAQ
Artesunate plus Amodiaquine
Drug: Artesunate plus Amodiaquine
Artesunate 50 mg and Amodiaquine 153 mg co-blister tablets: 3 days once daily weight-adjusted dosing according to manufacturer
Other Name: Arsucam®

Detailed Description:

Childhood mortality related to Plasmodium falciparum malaria is on the rise with more than 1 million deaths per year in Sub-Saharan Africa. In the context of growing drug-resistance to antimalarials health officials are calling for rapid replacement of failing drugs by combining antimalarial drugs. Artemisinin Combination Antimalarial Therapies (ACTs) are in the focus of malaria control programmes and are recommended for first-line treatment in African countries. ACTs have been reported to be highly effective as artemisinin derivatives cause a rapid and substantial decrease in the parasite load when used for treating patients with malaria and resistance to artemisinin is still lacking. However, the short half-lives of artemisinins result in frequent recrudescent infections when used alone and therefore, much interest lays on the choice of the combination partner drug. ACTs also have been proposed as a means of reducing transmission by the reduction of gametocytes and of delaying the spread of drug resistance and prolonging the therapeutic life span of. Nevertheless, drug resistance of parasites to the respective partner drug is a matter of concern. Artesunate-amodiaquine (AQ) and artemether-lumefantrine (AL) are two registered fixed-dose artemisinin combination chemotherapies used in Africa which are GMP-manufactured at industrial scale. There is still limited data from randomised, controlled trials to support the general effectiveness of these two ACTs in Africa, including Ghana. More data is needed to compare these two therapies to make evidence-based first-line treatment decisions. Importantly, it is difficult to predict how combination therapy may affect the spread of drug resistance and monitoring drug resistance markers should be embedded in these trials to guide drug policy decision.

The aim of this open-labelled, randomised drug trial is to compare the effectiveness and safety of artesunate-amodiaquine (Arsucam®) against artemether plus lumefantrine (Coartem®) for the treatment of children under five years of age with uncomplicated Plasmodium falciparum malaria.

  Eligibility

Ages Eligible for Study:   6 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female outpatients aged 6 months to 59 months
  • Absence of severe malnutrition
  • A slide-confirmed P. falciparum asexual parasitaemia between 2,000/µl and 200,000/µl
  • A measured axillary temperature ≥ 37.5 °C or rectal/tympanic temperature ≥ 38.0 °C
  • Absence of general danger signs (unable to drink; repeated vomiting; recent history of convulsions; lethargic or unconscious state; unable to stand up or to sit)
  • Ability to tolerate oral therapy
  • Permanent residence in study area
  • Informed consent by the legal representative of the subject, if possible, the parents

Exclusion Criteria:

  • Adequate anti-malarial treatment within the previous 7 days
  • Antibiotic treatment for a current infection
  • Previous participation in a clinical trial
  • Haemoglobin < 5 g/dl
  • Leucocyte count: > 15000/µl
  • Mixed plasmodial infection
  • Severe malaria as defined by WHO recommendations
  • Any other severe underlying disease (cardiac, renal, hepatic diseases, malnutrition, known HIV infection) or concomitant disease masking assessment of response
  • History of allergy or intolerance against trial medication
  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: NCT00374205

Locations
Ghana
Agogo Presbyterian Hospital
Agogo, Asante Akim North District, Ghana
Sponsors and Collaborators
Bernhard Nocht Institute for Tropical Medicine
Presbyterian Health Service (PHS)
Kumasi Centre for Collaborative Research (KCCR)
School of Medical Sciences Kumasi (SMS/KNUST)
Investigators
Principal Investigator: Daniel Ansong, MD School of Medical Science (SMS), Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana
  More Information

Additional Information:
Publications:

ClinicalTrials.gov Identifier: NCT00374205     History of Changes
Other Study ID Numbers: 01KA22062006
Study First Received: September 8, 2006
Last Updated: November 26, 2007
Health Authority: Ghana: Ministry of Health
Germany: Ethics Commission

Keywords provided by Bernhard Nocht Institute for Tropical Medicine:
Ghana
Effectiveness
Safety
Drug-Resistance
ACT
Coartem
Arsucam

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Amodiaquine
Artemether
Artemisinins
Artesunate
Lumefantrine
Artemether-lumefantrine combination
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 August 20, 2014