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Kintampo Trial of Combination Therapy for Malaria

This study has been completed.
Sponsor:
Collaborator:
Kintampo Health Research Centre, Ghana
Information provided by:
Gates Malaria Partnership
ClinicalTrials.gov Identifier:
NCT00119145
First received: July 4, 2005
Last updated: February 7, 2008
Last verified: February 2008
  Purpose

Case management is one of the key strategies for malaria control in most endemic countries. Plasmodium falciparum malaria is becoming resistant to commonly used and cheap antimalarial drugs such as chloroquine, amodiaquine, and sulfadoxine-pyrimethamine (SP). Thus the safety and efficacy of new anti-malarial drugs need to be tested in sites with well-characterised malariometric indices in order to make appropriate treatment policies.

Artemisinin-based combination chemotherapies have been documented to consistently produce faster relief of clinical symptoms and parasite clearance in uncomplicated falciparum malaria than any other currently used antimalarial drugs. So far, artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AR-LM) are the only two registered fixed-dose artemisinin combination chemotherapies produced at industrial scale, with good manufacturing practices and already used in Africa. Several African countries, including Ghana, are therefore introducing either AS-AQ or AR-LM as first-line antimalarials or evaluating the case for such a change. Clearly, a direct comparison of both the safety and efficacy profiles of the two combinations under different epidemiological conditions is urgently needed to guide informed decisions on the most appropriate antimalarial first-line treatment regimen.

This study aims to evaluate the efficacy and safety of artesunate-amodiaquine combination therapy, artemether-lumefantrine, and artesunate-lapdap in an open-labelled, randomised, non-inferiority drug trial.

The study results will inform future decisions on first- and second-line treatments for uncomplicated P. falciparum malaria with respect to efficacy and safety in Ghana.


Condition Intervention Phase
Malaria
Drug: artesunate-amodiaquine
Drug: coartem
Drug: artesunate-lapdap
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 Non-Inferiority, Open-Labelled, Randomised Trial Of The Efficacy And Safety Of Artesunate-Amodiaquine, Artemether-Lumefantrine, And Artesunate-Lapdap For Treatment Of Uncomplicated P. Falciparum Malaria Among Children In Ghana

Resource links provided by NLM:


Further study details as provided by Gates Malaria Partnership:

Primary Outcome Measures:
  • adequate clinical and Parasitological response (ACPR)by day 28.

Secondary Outcome Measures:
  • Parasitological cure rate by day 14
  • Parasitological cure rate by day 28
  • Clinical cure rates by days 14 and 28
  • Incidence rates of adverse events
  • Gametocyte carriage at days 7, 14 and 28

Estimated Enrollment: 510
Study Start Date: June 2005
Study Completion Date: May 2006
  Hide Detailed Description

Detailed Description:

A study funded by the GMP-LSHTM in the Kintampo district of Ghana is currently assessing the efficacy of SP as part of a comprehensive process of characterising the site into the patterns of seasonal dynamics of P. falciparum transmission, infection, and morbidity. The initial results from this study have demonstrated a high parasitological failure rate(18%) on day 14 of treatment, an indication that SP is no longer suitable for use in Ghana. Artesunate combination therapies (ACTs) have been found to be efficacious and safe, producing rapid clearance of parasites and malaria symptoms; they are very well tolerated. Lapdap is a newly registered, relatively cheap antimalarial with short half-life and has been found to be highly efficacious in strict trial conditions for treatment of acute uncomplicated falciparum infections in endemic sites in Africa. Despite the rapid clearance of lapdap, children treated with this drug did not have higher incidence of malaria episodes than those treated with SP though haematological adverse effects have been documented to be more common with lapdap than with SP. At present, the fixed-dose combination regimens of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AR-LM) are the only two registered artemisinin combination chemotherapies produced at industrial scale, with good manufacturing practices and already used in Africa. Several African countries are introducing either AS-AQ or AR-LM as first-line antimalarials or evaluating the case for such a change. Ghana, has just changed its antimalarial drug policy to artesunate-amodiaquine combination therapy (AS-AQ) as first line drug. The selection of this new ACT has been driven partly by cost of treatment, but a critical look at the safety and efficacy of ACTs in Ghana has yet to be done.

This study aims to evaluate the efficacy and safety of artesunate-amodiaquine combination therapy (AS-AQ), Artemether-lumefantrine (Coartem), and Artesunate-lapdap) in a drug non-inferiority study.

Objectives

Primary objective:

• To evaluate the efficacy of artesunate-amodiaquine versus artemether-lumefantrine, versus artesunate-lapdap in the treatment of children aged 6 months to ten years, infected with uncomplicated falciparum malaria, at the paediatric outpatient clinic in the Kintampo hospital.

Secondary objectives:

• To evaluate the safety of artesunate-amodiaquine versus artemether-lumefantrine, versus artesunate-lapdap in the treatment of children 6 months to ten years with uncomplicated falciparum malaria.

Study design and methods

Study site: This study is being conducted in Kintampo district in the middle belt of Ghana where the investigators in the Kintampo Health Research Centre are located. Kintampo Health Research Centre (KHRC), one of three research centres under the Health Research Unit (HRU) of the Ghana Health Service, Ghana, lies within the forest-savannah, transitional ecological zone in the Brong Ahafo Region of Ghana.

Study design:

This is a randomised, open-labelled, non-inferiority drug trial. At the Kintampo district hospital, 510 paediatric outpatients (refer sample size calculation) with uncomplicated P. falciparum malaria and aged between 6 months and 10 years will be recruited and randomly assigned to one of the three study arms: (i) Artesunate-Amodiaquine (AS-AQ), (ii) Artemether-Lumefantrine (AR-LM), or (iii) Artesunate-lapdap (AS-LP). The classification of clinical and parasitological responses will follow the relevant WHO protocol for areas of intense transmission. Follow-up, however, will be extended beyond day 14 up to day 28 to increase the sensitivity of the in vivo test. PCR-based genotyping comparing pairs of parasite isolates from day 0 and day of asexual parasite reappearance will be used to distinguish between recrudescence and re-infection.

  Eligibility

Ages Eligible for Study:   6 Months to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 6 months to 10 years
  • Body weight >5 kg
  • Uncomplicated P. falciparum malaria
  • Mono-infection with P. falciparum
  • Asexual parasite density 2,000 to 200,000 parasites/µl
  • Haemoglobin ≥7.0 g/dL
  • Axillary temperature ≥37.5ºC or history of fever in preceding 24 hr
  • Ability to tolerate oral therapy
  • Residence in study area

Exclusion Criteria:

  • Haemoglobin <7.0 g/dL
  • Leucocyte count: >15,000/µL
  • G6PD deficiency
  • Mixed malaria infections
  • Danger signs (unable to drink; repeated vomiting; recent history of convulsions; lethargic or unconscious state; unable to stand up or to sit) and signs of severe malaria as defined by WHO
  • Any other severe underlying disease (cardiac, renal, hepatic diseases, malnutrition, known HIV infection)
  • Concomitant disease masking assessment of response, e.g. known or suspected hearing impairments
  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: NCT00119145

Locations
Ghana
Kintampo Health Research Centre
Kintampo, Brong Ahafo Region, Ghana
Sponsors and Collaborators
Gates Malaria Partnership
Kintampo Health Research Centre, Ghana
Investigators
Principal Investigator: Seth Owusu-Agyei, PhD London School of Hygiene and Tropical Medicine
Principal Investigator: Daniel Chandramohan, MBBS, PhD London School of Hygiene and Tropical Medicine
Principal Investigator: Brian M Greenwood, FRCP, FRS London School of Hygiene and Tropical Medicine
  More Information

No publications provided by Gates Malaria Partnership

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00119145     History of Changes
Other Study ID Numbers: ITDCVG44
Study First Received: July 4, 2005
Last Updated: February 7, 2008
Health Authority: Ghana: Ministry of Health

Keywords provided by Gates Malaria Partnership:
antimalarial drugs
efficacy
safety
trial

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Amodiaquine
Artemisinins
Artesunate
Amebicides
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014