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

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.

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: Coarsucam; Drug: Coartem

• Study Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 4

Contacts and Locations

Study Locations

• Uganda
  • Kampala, Uganda
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PCR corrected and uncorrected clinical and parasitological cure rate	At Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Fever and parasitological clearance evaluation by measuring the axillary temperature and monitoring paratesimia	At the first attack
Proportion of afebrile patients and proportion of patients without parasites	At Day 3 (following attacks)
Evolution of baseline symptoms (Clinical efficacy measure)	During the study conduct
Number of residual tablets in blisters (compliance)	At the end of the study treatment
Treatment incidence density: comparison of the number of malaria attacks between the 2 arms	During the 2 years of follow-up
Mean delay between 2 attacks	during the 2 years of follow-up
Incidence and intensity of recorded AE	from the informed consent signed up to the end of the study
Biological tolerability (Hb, Bilirubin, ALAT, Creatinine, Leucocytes, Neutrophils and Platelets count)	During the study conduct
PCR corrected and uncorrected clinical and parasitological cure rate	At Day 42

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Valerie Lemeyre, Sanofi

Publications and helpful links

General Publications

• Yeka A, Lameyre V, Afizi K, Fredrick M, Lukwago R, Kamya MR, Talisuna AO. Efficacy and safety of fixed-dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children. PLoS One. 2014 Dec 1;9(12):e113311. doi: 10.1371/journal.pone.0113311. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: June 16, 2008
• First Submitted That Met QC Criteria: June 17, 2008
• First Posted (Estimate): June 18, 2008

Study Record Updates

• Last Update Posted (Estimate): June 29, 2010
• Last Update Submitted That Met QC Criteria: June 28, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: ARAMF_L_02661