Clinical trial NCT01378286: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-06-22
Enrollment: 380
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Assessment of clinical and parasitological efficacy based on temperature and parasitemia after Polymerase chain reaction (PCR) correction
timeFrame: 28 days
Secondary outcomes:
measure: 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
timeFrame: up to a maximum of 42 days
measure: Number of patients without parasite
timeFrame: up to a maximum of 42 days
measure: Number of patients without fever
timeFrame: up to a maximum of 42 days
measure: Number of patients with gametocytes
timeFrame: up to a maximum of 42 days
measure: Change from baseline in Haemoglobin levels
timeFrame: Day 7, Day 28
measure: Incidence and severity of adverse events collected
timeFrame: up to a maximum of 42 days
measure: ECG (QTc) changes in patients group aged >= 10 years from baseline
timeFrame: Day 3, Day 28
measure: Assessment of biological tolerability (bilirubin, ALAT, Creatinine, Leukocytes, Neutrophils and platelets count) from baseline
timeFrame: up to a maximum of 42 days
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Administrative office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
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.