Cohort Study in Uganda Comparing Artesunate + Amiodaquine (Coarsucam) Versus Artemether + Lumenfantrine (Coartem) in the Treatment of Repeated Uncomplicated Plasmodium Falciparum Malaria Attacks (SMART-CURE)

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00699920
First received: June 16, 2008
Last updated: June 28, 2010
Last verified: June 2010
  Purpose

Primary objective is to demonstrate the non-inferiority of PCR (Polymerase Chain Reaction) adjusted adequate clinical and parasitological response at Day 28 of Coarsucam versus Coartem, based on the first malaria attack of each patient.

Secondary objectives:

For the first attack:

To compare the 2 groups of treatment in terms of:

  • Day 42 efficacy
  • Parasitological and fever clearance
  • Clinical and Biological tolerability
  • Evolution of gametocyte carriage

For attack 2nd and following:

To compare the 2 groups of treatment in terms of:

  • Day 28 and Day 42 clinical and parasitological effectiveness
  • Clinical and Biological tolerability
  • Proportion of patients without fever at Day 3
  • Proportion of patients without parasites at Day 3
  • Evolution of gametocyte carriage
  • Compliance

During the total follow up of the cohort:

To compare the 2 groups of treatment in terms of:

  • Treatment incidence density
  • Impact of repeated treatment on clinical and biological tolerability
  • Impact on anaemia
  • Impact on Hackett score.

Condition Intervention Phase
Malaria
Drug: Coarsucam
Drug: Coartem
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 Randomised Study to Compare a Fixed Dose Combination of Artesunate Plus Amiodaquine (Coarsucam) Versus a Fixed Dose Combination of Artemether Plus Lumefantrine (Coartem) in the Treatment of Repeated Uncomplicated Plasmodium Falciparum Malaria Attacks Occurring During the 2 Years of Follow-up, in Children in Uganda.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • PCR corrected and uncorrected clinical and parasitological cure rate [ Time Frame: At Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fever and parasitological clearance evaluation by measuring the axillary temperature and monitoring paratesimia [ Time Frame: At the first attack ] [ Designated as safety issue: No ]
  • Proportion of afebrile patients and proportion of patients without parasites [ Time Frame: At Day 3 (following attacks) ] [ Designated as safety issue: No ]
  • Evolution of baseline symptoms (Clinical efficacy measure) [ Time Frame: During the study conduct ] [ Designated as safety issue: No ]
  • Number of residual tablets in blisters (compliance) [ Time Frame: At the end of the study treatment ] [ Designated as safety issue: No ]
  • Treatment incidence density: comparison of the number of malaria attacks between the 2 arms [ Time Frame: During the 2 years of follow-up ] [ Designated as safety issue: No ]
  • Mean delay between 2 attacks [ Time Frame: during the 2 years of follow-up ] [ Designated as safety issue: No ]
  • Incidence and intensity of recorded AE [ Time Frame: from the informed consent signed up to the end of the study ] [ Designated as safety issue: No ]
  • Biological tolerability (Hb, Bilirubin, ALAT, Creatinine, Leucocytes, Neutrophils and Platelets count) [ Time Frame: During the study conduct ] [ Designated as safety issue: No ]
  • PCR corrected and uncorrected clinical and parasitological cure rate [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

Enrollment: 413
Study Start Date: June 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Coarsucam double-layer artesunate/amiodaquine tablets
Drug: Coarsucam
Oral route, once daily, dose according to bodyweight range Duration of treatment: 3 days
Active Comparator: 2
Coartem (artemether/lumefantrine) fixed-dose combination tablets
Drug: Coartem
Oral route, twice daily, dose according to bodyweight range Duration of treatment: 3 days

  Eligibility

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

Inclusion Criteria:

Specific inclusion criteria for initial enrollment:

  • Confirmed mono infection with Plasmodium falciparum, with parasite density ≥2000 asexual forms per µl of blood,

Inclusion criteria for each attacks:

  • Body weight ≥5 kg
  • Able to be treated by oral route
  • Fever (axillary temperatur ≥37.5 degrees Celsius) at D0 or history of fever within the previous 24 hours
  • Confirmed Plasmodium falciparum infection with positive paratesimia
  • Haemoglobin value ≥5.0 g/dl

Exclusion Criteria:

Specific exclusion criteria for initial enrollment:

  • Patient participating in another ongoing clinical trial
  • Allergy to one of the investigational medicinal products
  • History of hepatic and (or) haematological impairment during treatment with amodiaquine
  • History of cardiac disease
  • Concomitant febrile illness

Exclusion criteria for each attacks:

  • Presence of at least one danger sign of malaria: recent history of convulsions (1-2 within 24h), unconsciousness state, lethargy, unable to drink or breast feed, vomiting everything, unable to stand/sit due to weakness
  • Severe concomitant disease or known disturbances of electrolyte balance such as hypokalaemia or hypomagnesaemia
  • Intake of medication metabolized by cytochrome CYP 2D6 (e.g. metoprolol, flecainide, imipramine, amitriptyline, clomipramine) at the time of inclusion
  • Intake of drugs known to inhibit CYP 2A6 (e.g. methoxsalem, pilocarpine, tranylcypromine) and/or 2C8 cytochromes (e.g. trimethoprim, ritonavir, ketoconazole, montelukast, gemfibrozil) at the time of inclusion
  • Intake of medication known to prolong the QTc interval, such as class IA and III antiarrythmics, neuroleptics, antidepressant agents, certain antibiotics including drugs in the macrolide class, fluoroquinolones, imidazole and triazole, antifungal agents, certain non-sedative anthistamines (terfenadine, astemizole) and cisapride at the time of inclusion
  • Patient having received artesunate + amiodaquine or artemether + lumefantrine at suitable dosage within the previous 2 weeks.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  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: NCT00699920

Locations
Uganda
Sanofi-aventis administrative office
Kampala, Uganda
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Valerie Lemeyre Sanofi
  More Information

No publications provided

Responsible Party: Medical Affairs Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00699920     History of Changes
Other Study ID Numbers: ARAMF_L_02661
Study First Received: June 16, 2008
Last Updated: June 28, 2010
Health Authority: Uganda: National Council for Science and Technology
Uganda: National Drug Authority

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artemether
Artesunate
Lumefantrine
Artemether-lumefantrine combination
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Amebicides

ClinicalTrials.gov processed this record on August 27, 2014