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

Primary Purpose

Malaria

Status

Completed

Phase

Phase 4

Locations

Uganda

Study Type

Interventional

Intervention

Coarsucam

Coartem

About this trial

This is an interventional treatment trial for Malaria

Eligibility Criteria

6 Months - 59 Months (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Sanofi-aventis administrative office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm Description

Coarsucam double-layer artesunate/amiodaquine tablets

Coartem (artemether/lumefantrine) fixed-dose combination tablets

Outcomes

Primary Outcome Measures

PCR corrected and uncorrected clinical and parasitological cure rate

Secondary Outcome Measures

Fever and parasitological clearance evaluation by measuring the axillary temperature and monitoring paratesimia

Proportion of afebrile patients and proportion of patients without parasites

Evolution of baseline symptoms (Clinical efficacy measure)

Number of residual tablets in blisters (compliance)

Treatment incidence density: comparison of the number of malaria attacks between the 2 arms

Mean delay between 2 attacks

Incidence and intensity of recorded AE

Biological tolerability (Hb, Bilirubin, ALAT, Creatinine, Leucocytes, Neutrophils and Platelets count)

PCR corrected and uncorrected clinical and parasitological cure rate

Full Information

NCT ID

NCT00699920

First Posted

June 16, 2008

Last Updated

June 28, 2010

Sponsor

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT00699920

Brief Title

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

Acronym

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.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2010

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

June 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Sanofi

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

413 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Coarsucam double-layer artesunate/amiodaquine tablets

Arm Title

Arm Type

Active Comparator

Arm Description

Coartem (artemether/lumefantrine) fixed-dose combination tablets

Intervention Type

Drug

Intervention Name(s)

Coarsucam

Intervention Description

Oral route, once daily, dose according to bodyweight range Duration of treatment: 3 days

Intervention Type

Drug

Intervention Name(s)

Coartem

Intervention Description

Oral route, twice daily, dose according to bodyweight range Duration of treatment: 3 days

Primary Outcome Measure Information:

Title

PCR corrected and uncorrected clinical and parasitological cure rate

Time Frame

At Day 28

Secondary Outcome Measure Information:

Title

Fever and parasitological clearance evaluation by measuring the axillary temperature and monitoring paratesimia

Time Frame

At the first attack

Title

Proportion of afebrile patients and proportion of patients without parasites

Time Frame

At Day 3 (following attacks)

Title

Evolution of baseline symptoms (Clinical efficacy measure)

Time Frame

During the study conduct

Title

Number of residual tablets in blisters (compliance)

Time Frame

At the end of the study treatment

Title

Treatment incidence density: comparison of the number of malaria attacks between the 2 arms

Time Frame

During the 2 years of follow-up

Title

Mean delay between 2 attacks

Time Frame

during the 2 years of follow-up

Title

Incidence and intensity of recorded AE

Time Frame

from the informed consent signed up to the end of the study

Title

Biological tolerability (Hb, Bilirubin, ALAT, Creatinine, Leucocytes, Neutrophils and Platelets count)

Time Frame

During the study conduct

Title

PCR corrected and uncorrected clinical and parasitological cure rate

Time Frame

At Day 42

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

59 Months

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Valerie Lemeyre

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

Sanofi-aventis administrative office

City

Kampala

Country

Uganda

12. IPD Sharing Statement

Citations:

PubMed Identifier

25436614

Citation

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.

Results Reference

derived

Learn more about this trial

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

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