Efficacy and Tolerability of Artesunate Amodiaquine Versus Chloroquine in the Treatment of Uncomplicated Plasmodium Vivax Malaria
Primary Purpose
Malaria
Status
Completed
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
ARTESUNATE + AMODIAQUINE
Chloroquine
Sponsored by
About this trial
This is an interventional treatment trial for Malaria
Eligibility Criteria
Inclusion criteria:
- Adults and children over 6 months old and bodyweight > 5 kg
- Able to be treated by oral route
- Axillary temperature ≥ 37,5 C or history of fever during the previous 2 days
- Symptomatic biologically confirmed Plasmodium vivax mono-infection, with parasitemia from 250 to 100000 parasites /µl of blood
- Written informed consent of the patients and for children written informed consent of the parents/legal representative for children. Children able to understand the objectives and the risks of the study will sign an assent form.
Exclusion criteria:
- Known project of leaving the investigator site area during the follow-up period (42 days)
- Hypersensitivity to one of the investigational medicinal products or to any of the excipients
- Intake of an antimalarial treatment in the previous 30 days
- History of hepatic and (or) haematological impairment during treatment with amodiaquine
- Blurred vision suggesting a retinopathy
- Presence of at least one danger sign of malaria
- Pregnant or breast-feeding women
- Women with childbearing potential not willing to use an effective contraceptive method(s) for the duration of the study
- Known severe concomitant or underlying disease
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Administrative office
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
artesunate/amodiaquine
chloroquine
Arm Description
artesunate (AS) / amodiaquine (AQ) as fixed dose combination 1 tablet of AS 25mg/ AQ 67,5mg or AS 50mg/AQ 135mg or AS 100mg/ AQ 270mg or 2 tablets of AS 100mg/ AQ 270mg dose according to bodyweight Once daily 3 days of treatment
150mg tablets 25mg/kg in 3 days (10mg/kg on day 1 and 7,5 mg/kg on days 2 and 3) dose according to bodyweight Once daily 3 days of treatment
Outcomes
Primary Outcome Measures
Assessment of clinical and parasitological efficacy based on temperature and parasitemia after Polymerase chain reaction (PCR) correction
Secondary Outcome Measures
Assessment of clinical and parasitological efficacy based on temperature and parasitemia before and after PCR correction at D14 and D42 and before PCR correction at D28
Number of patients without parasite
Number of patients without fever
Number of patients with gametocytes
Change from baseline in Haemoglobin levels
Incidence and severity of adverse events collected
ECG (QTc) changes in patients group aged >= 10 years from baseline
Assessment of biological tolerability (bilirubin, ALAT, Creatinine, Leukocytes, Neutrophils and platelets count) from baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01378286
Brief Title
Efficacy and Tolerability of Artesunate Amodiaquine Versus Chloroquine in the Treatment of Uncomplicated Plasmodium Vivax Malaria
Official Title
A Randomised Comparative Study to Assess the Efficacy and Tolerability of Blood Schizonticidal Treatments With Artesunate Amodiaquine Winthrop® / Coarsucam (ASAQ) Versus Chloroquine (CQ) for Uncomplicated Plasmodium Vivax Monoinfection Malaria
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Primary Objective:
- To demonstrate the non-inferiority of corrected adequate clinical and parasitological response at Day 28 of Artesunate Amodiaquine (ASAQ) versus chloroquine
Secondary Objectives:
To assess the non inferiority on the same way as the main criteria:
at Day 28 before corrected cure rate
at Day 14 and Day 42 before and after corrected cure rate
To compare the two groups of treatment in terms of:
Efficacy:
Proportion of aparasitaemic patients at 24, 48 an 72 hours
Proportion of afebrile patients at 24, 48 and 72 hours
Percentage of gametocyte carriers during follow-up
Evolution of the mean of gametocytes during the 42 days of follow-up
Evolution of haemoglobin value between Day 0 and Day 7, Day 0 and Day 28
Clinical and biological tolerability:
Proportion of any adverse event
Biological safety: haematology (Red blood cells, Haemoglobin, White Blood Cells, neutrophils, platelets), biochemistry (creatinine, transaminases (alanine amino transferase/ALT), bilirubins)
ECG (electro encephalogram) (Day 0, Day 3,Day 28) only for patients 10 years old and above
Detailed Description
Each patient will be followed for a period of 42 days
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 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
380 (Actual)
8. Arms, Groups, and Interventions
Arm Title
artesunate/amodiaquine
Arm Type
Experimental
Arm Description
artesunate (AS) / amodiaquine (AQ) as fixed dose combination
1 tablet of AS 25mg/ AQ 67,5mg or AS 50mg/AQ 135mg or AS 100mg/ AQ 270mg or 2 tablets of AS 100mg/ AQ 270mg dose according to bodyweight Once daily 3 days of treatment
Arm Title
chloroquine
Arm Type
Active Comparator
Arm Description
150mg tablets 25mg/kg in 3 days (10mg/kg on day 1 and 7,5 mg/kg on days 2 and 3) dose according to bodyweight Once daily 3 days of treatment
Intervention Type
Drug
Intervention Name(s)
ARTESUNATE + AMODIAQUINE
Intervention Description
Pharmaceutical form:
Route of administration:
Intervention Type
Drug
Intervention Name(s)
Chloroquine
Intervention Description
Pharmaceutical form:tablet Route of administration: oral
Primary Outcome Measure Information:
Title
Assessment of clinical and parasitological efficacy based on temperature and parasitemia after Polymerase chain reaction (PCR) correction
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Assessment of clinical and parasitological efficacy based on temperature and parasitemia before and after PCR correction at D14 and D42 and before PCR correction at D28
Time Frame
up to a maximum of 42 days
Title
Number of patients without parasite
Time Frame
up to a maximum of 42 days
Title
Number of patients without fever
Time Frame
up to a maximum of 42 days
Title
Number of patients with gametocytes
Time Frame
up to a maximum of 42 days
Title
Change from baseline in Haemoglobin levels
Time Frame
Day 7, Day 28
Title
Incidence and severity of adverse events collected
Time Frame
up to a maximum of 42 days
Title
ECG (QTc) changes in patients group aged >= 10 years from baseline
Time Frame
Day 3, Day 28
Title
Assessment of biological tolerability (bilirubin, ALAT, Creatinine, Leukocytes, Neutrophils and platelets count) from baseline
Time Frame
up to a maximum of 42 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Adults and children over 6 months old and bodyweight > 5 kg
Able to be treated by oral route
Axillary temperature ≥ 37,5 C or history of fever during the previous 2 days
Symptomatic biologically confirmed Plasmodium vivax mono-infection, with parasitemia from 250 to 100000 parasites /µl of blood
Written informed consent of the patients and for children written informed consent of the parents/legal representative for children. Children able to understand the objectives and the risks of the study will sign an assent form.
Exclusion criteria:
Known project of leaving the investigator site area during the follow-up period (42 days)
Hypersensitivity to one of the investigational medicinal products or to any of the excipients
Intake of an antimalarial treatment in the previous 30 days
History of hepatic and (or) haematological impairment during treatment with amodiaquine
Blurred vision suggesting a retinopathy
Presence of at least one danger sign of malaria
Pregnant or breast-feeding women
Women with childbearing potential not willing to use an effective contraceptive method(s) for the duration of the study
Known severe concomitant or underlying disease
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
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Administrative office
City
Sao Paulo
Country
Brazil
12. IPD Sharing Statement
Citations:
PubMed Identifier
27988484
Citation
Siqueira AM, Alencar AC, Melo GC, Magalhaes BL, Machado K, Alencar Filho AC, Kuehn A, Marques MM, Manso MC, Felger I, Vieira JL, Lameyre V, Daniel-Ribeiro CT, Lacerda MV. Fixed-Dose Artesunate-Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial. Clin Infect Dis. 2017 Jan 15;64(2):166-174. doi: 10.1093/cid/ciw706. Epub 2016 Oct 20. Erratum In: Clin Infect Dis. 2017 May 15;64(10):1468.
Results Reference
derived
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Efficacy and Tolerability of Artesunate Amodiaquine Versus Chloroquine in the Treatment of Uncomplicated Plasmodium Vivax Malaria
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