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

Malaria Clinical Trial

— SMART-CURE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00699920
• Other study ID #: ARAMF_L_02661
• Status: Completed
• Phase: Phase 4
• First received: June 16, 2008
• Last updated: June 28, 2010
• Start date: June 2008
• Est. completion date: June 2010

Study information

• Verified date: June 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: National Council for Science and TechnologyUganda: National Drug Authority
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 413
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 59 Months

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• Coarsucam
Oral route, once daily, dose according to bodyweight range Duration of treatment: 3 days
• Coartem
Oral route, twice daily, dose according to bodyweight range Duration of treatment: 3 days

Locations

Country	Name	City	State
Uganda	Sanofi-aventis administrative office	Kampala

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PCR corrected and uncorrected clinical and parasitological cure rate		At Day 28	No
Secondary	Fever and parasitological clearance evaluation by measuring the axillary temperature and monitoring paratesimia		At the first attack	No
Secondary	Proportion of afebrile patients and proportion of patients without parasites		At Day 3 (following attacks)	No
Secondary	Evolution of baseline symptoms (Clinical efficacy measure)		During the study conduct	No
Secondary	Number of residual tablets in blisters (compliance)		At the end of the study treatment	No
Secondary	Treatment incidence density: comparison of the number of malaria attacks between the 2 arms		During the 2 years of follow-up	No
Secondary	Mean delay between 2 attacks		during the 2 years of follow-up	No
Secondary	Incidence and intensity of recorded AE		from the informed consent signed up to the end of the study	No
Secondary	Biological tolerability (Hb, Bilirubin, ALAT, Creatinine, Leucocytes, Neutrophils and Platelets count)		During the study conduct	No
Secondary	PCR corrected and uncorrected clinical and parasitological cure rate		At Day 42	No