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Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: a randomized, open-label study.

Chandra R, Ansah P, Sagara I, Sie A, Tiono AB, Djimde AA, Zhao Q, Robbins J, Penali LK, Ogutu B - Malar. J. (2015)

Bottom Line: Non-inferiority was concluded if the lower bound of the 95% confidence interval comparing the two groups was 10 percentage points or greater.Adverse events were more common in subjects treated with AZCQ.In this study, non-inferiority of AZCQ to AL was not demonstrated.

View Article: PubMed Central - PubMed

Affiliation: Novartis, Cambridge, MA, USA. richa.chandra@novartis.com.

ABSTRACT

Background: This randomized, open-label study was conducted to establish the non-inferiority of a combination of azithromycin (AZ) and chloroquine (CQ) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in children from six sites in sub-Saharan Africa.

Methods: Children with uncomplicated Plasmodium falciparum malaria between six and 59 months of age were randomized 1:1 to either AZCQ (30 mg/kg AZ + 10 mg/kg CQ base) or AL per prescribing information for three days (Days 0, 1, 2). Each site could enrol in the study population once the treatment of uncomplicated malaria in five children five to 12 years of age was deemed to be effective and well tolerated. The primary efficacy evaluation was the proportion of subjects in both the modified intent-to-treat (MITT) and per-protocol (PP) populations with an adequate clinical and parasitological response (PCR corrected) at Day 28. Non-inferiority was concluded if the lower bound of the 95% confidence interval comparing the two groups was 10 percentage points or greater.

Results: A total of 255 children were enrolled in the efficacy analysis (AZCQ, n = 124; AL, n = 131). The PCR corrected clearance rates were 89% (AZCQ) versus 98% (AL) for MITT, a difference of -9.10 (95% confidence interval; -16.02, -2.18) and 93% (AZCQ) versus 99% (AL) for PP, a difference of -6.08 (-12.10, -0.05). Early and late treatment failures were more common in subjects receiving AZCQ. Adverse events were more common in subjects treated with AZCQ. Drug concentrations obtained at specified time points following AZCQ administration had a large coefficient of variation partially due to sparse sampling with sample collection time window.

Conclusions: In this study, non-inferiority of AZCQ to AL was not demonstrated.

Trial registration: ClinicalTrials.gov NCT00677833 .

No MeSH data available.


Related in: MedlinePlus

Subject disposition (Cohort 2). AE = adverse event, AL = artemether-lumefantrine, AZCQ = azithromycin-chloroquine fixed-dose combination, MITT = modified intent-to-treat, PP = per protocol. *Includes 1 subject who discontinued treatment due to an AE.
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Fig1: Subject disposition (Cohort 2). AE = adverse event, AL = artemether-lumefantrine, AZCQ = azithromycin-chloroquine fixed-dose combination, MITT = modified intent-to-treat, PP = per protocol. *Includes 1 subject who discontinued treatment due to an AE.

Mentions: The primary study population included 255 subjects who were screened and randomized (Figure 1). After excluding subjects from the Ivory Coast, the MITT population included 246 subjects. One subject or their parent/legal guardian in the AZCQ group was no longer willing to participate and discontinued from the study, and one subject was lost to follow-up. Treatment discontinuation due to AEs occurred in seven subjects in the AZCQ group. Three subjects or their parent/legal guardian in the AL treatment group were no longer willing to participate and discontinued from the study, and one subject stopped treatment because of AEs.Figure 1


Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: a randomized, open-label study.

Chandra R, Ansah P, Sagara I, Sie A, Tiono AB, Djimde AA, Zhao Q, Robbins J, Penali LK, Ogutu B - Malar. J. (2015)

Subject disposition (Cohort 2). AE = adverse event, AL = artemether-lumefantrine, AZCQ = azithromycin-chloroquine fixed-dose combination, MITT = modified intent-to-treat, PP = per protocol. *Includes 1 subject who discontinued treatment due to an AE.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4358906&req=5

Fig1: Subject disposition (Cohort 2). AE = adverse event, AL = artemether-lumefantrine, AZCQ = azithromycin-chloroquine fixed-dose combination, MITT = modified intent-to-treat, PP = per protocol. *Includes 1 subject who discontinued treatment due to an AE.
Mentions: The primary study population included 255 subjects who were screened and randomized (Figure 1). After excluding subjects from the Ivory Coast, the MITT population included 246 subjects. One subject or their parent/legal guardian in the AZCQ group was no longer willing to participate and discontinued from the study, and one subject was lost to follow-up. Treatment discontinuation due to AEs occurred in seven subjects in the AZCQ group. Three subjects or their parent/legal guardian in the AL treatment group were no longer willing to participate and discontinued from the study, and one subject stopped treatment because of AEs.Figure 1

Bottom Line: Non-inferiority was concluded if the lower bound of the 95% confidence interval comparing the two groups was 10 percentage points or greater.Adverse events were more common in subjects treated with AZCQ.In this study, non-inferiority of AZCQ to AL was not demonstrated.

View Article: PubMed Central - PubMed

Affiliation: Novartis, Cambridge, MA, USA. richa.chandra@novartis.com.

ABSTRACT

Background: This randomized, open-label study was conducted to establish the non-inferiority of a combination of azithromycin (AZ) and chloroquine (CQ) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in children from six sites in sub-Saharan Africa.

Methods: Children with uncomplicated Plasmodium falciparum malaria between six and 59 months of age were randomized 1:1 to either AZCQ (30 mg/kg AZ + 10 mg/kg CQ base) or AL per prescribing information for three days (Days 0, 1, 2). Each site could enrol in the study population once the treatment of uncomplicated malaria in five children five to 12 years of age was deemed to be effective and well tolerated. The primary efficacy evaluation was the proportion of subjects in both the modified intent-to-treat (MITT) and per-protocol (PP) populations with an adequate clinical and parasitological response (PCR corrected) at Day 28. Non-inferiority was concluded if the lower bound of the 95% confidence interval comparing the two groups was 10 percentage points or greater.

Results: A total of 255 children were enrolled in the efficacy analysis (AZCQ, n = 124; AL, n = 131). The PCR corrected clearance rates were 89% (AZCQ) versus 98% (AL) for MITT, a difference of -9.10 (95% confidence interval; -16.02, -2.18) and 93% (AZCQ) versus 99% (AL) for PP, a difference of -6.08 (-12.10, -0.05). Early and late treatment failures were more common in subjects receiving AZCQ. Adverse events were more common in subjects treated with AZCQ. Drug concentrations obtained at specified time points following AZCQ administration had a large coefficient of variation partially due to sparse sampling with sample collection time window.

Conclusions: In this study, non-inferiority of AZCQ to AL was not demonstrated.

Trial registration: ClinicalTrials.gov NCT00677833 .

No MeSH data available.


Related in: MedlinePlus