Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial

Johan Ursing, Lars Rombo, Amabelia Rodrigues, Poul-Erik Kofoed

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Resumé

BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria.

METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days to children aged 6 months-15 years with uncomplicated P. falciparum mono-infection. Intake was observed and AL was given with milk. Children were seen on days 0, 1, 2 and 3 and then weekly days 7-42. Recurring P. falciparum were classified as recrudescence or new infections by genotyping. Between November 2012 and July 2015, 312 children were randomised to AL (n = 155) or DP (n = 157). The day 42 PCR adjusted per protocol adequate clinical and parasitological responses were 95% and 100% in the AL and DP groups respectively, Mantel-Haenszel weighted odds ratio (OR) 0.22 (95% CI 0-0.68), p = 0.022. In a modified intention to treat analysis in which treatment failures day 0 and reinfections were also considered as treatment failures adequate clinical and parasitological responses were 94% and 97% (OR 0.42 [95% CI, 0.13-1.38], p = 0.15). Parasite clearance and symptom resolution were similar with both treatments.

CONCLUSIONS: Both treatments achieved the WHO recommended efficacy for antimalarials about to be adopted as policy. DP was not inferior to AL for treatment of uncomplicated P. falciparum malaria in Guinea-Bissau.

TRIAL REGISTRATION: ClinicalTrials.gov NTC01704508.

OriginalsprogEngelsk
Artikelnummere0161495
TidsskriftPLOS ONE
Vol/bind11
Udgave nummer9
Antal sider11
ISSN1932-6203
DOI
StatusUdgivet - 2016

Fingeraftryk

dihydroartemisinin
Guinea-Bissau
randomized clinical trials
Falciparum Malaria
Plasmodium falciparum
malaria
Labels
antimalarials
Malaria
odds ratio
Antimalarials
Treatment Failure
infection
genotyping
signs and symptoms (animals and humans)
clinical trials
Odds Ratio
piperaquine
artemether
Non-Randomized Controlled Trials

Citer dette

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title = "Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial",
abstract = "BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria.METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days to children aged 6 months-15 years with uncomplicated P. falciparum mono-infection. Intake was observed and AL was given with milk. Children were seen on days 0, 1, 2 and 3 and then weekly days 7-42. Recurring P. falciparum were classified as recrudescence or new infections by genotyping. Between November 2012 and July 2015, 312 children were randomised to AL (n = 155) or DP (n = 157). The day 42 PCR adjusted per protocol adequate clinical and parasitological responses were 95{\%} and 100{\%} in the AL and DP groups respectively, Mantel-Haenszel weighted odds ratio (OR) 0.22 (95{\%} CI 0-0.68), p = 0.022. In a modified intention to treat analysis in which treatment failures day 0 and reinfections were also considered as treatment failures adequate clinical and parasitological responses were 94{\%} and 97{\%} (OR 0.42 [95{\%} CI, 0.13-1.38], p = 0.15). Parasite clearance and symptom resolution were similar with both treatments.CONCLUSIONS: Both treatments achieved the WHO recommended efficacy for antimalarials about to be adopted as policy. DP was not inferior to AL for treatment of uncomplicated P. falciparum malaria in Guinea-Bissau.TRIAL REGISTRATION: ClinicalTrials.gov NTC01704508.",
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Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial. / Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia; Kofoed, Poul-Erik.

I: PLOS ONE, Bind 11, Nr. 9, e0161495, 2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial

AU - Ursing, Johan

AU - Rombo, Lars

AU - Rodrigues, Amabelia

AU - Kofoed, Poul-Erik

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria.METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days to children aged 6 months-15 years with uncomplicated P. falciparum mono-infection. Intake was observed and AL was given with milk. Children were seen on days 0, 1, 2 and 3 and then weekly days 7-42. Recurring P. falciparum were classified as recrudescence or new infections by genotyping. Between November 2012 and July 2015, 312 children were randomised to AL (n = 155) or DP (n = 157). The day 42 PCR adjusted per protocol adequate clinical and parasitological responses were 95% and 100% in the AL and DP groups respectively, Mantel-Haenszel weighted odds ratio (OR) 0.22 (95% CI 0-0.68), p = 0.022. In a modified intention to treat analysis in which treatment failures day 0 and reinfections were also considered as treatment failures adequate clinical and parasitological responses were 94% and 97% (OR 0.42 [95% CI, 0.13-1.38], p = 0.15). Parasite clearance and symptom resolution were similar with both treatments.CONCLUSIONS: Both treatments achieved the WHO recommended efficacy for antimalarials about to be adopted as policy. DP was not inferior to AL for treatment of uncomplicated P. falciparum malaria in Guinea-Bissau.TRIAL REGISTRATION: ClinicalTrials.gov NTC01704508.

AB - BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria.METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days to children aged 6 months-15 years with uncomplicated P. falciparum mono-infection. Intake was observed and AL was given with milk. Children were seen on days 0, 1, 2 and 3 and then weekly days 7-42. Recurring P. falciparum were classified as recrudescence or new infections by genotyping. Between November 2012 and July 2015, 312 children were randomised to AL (n = 155) or DP (n = 157). The day 42 PCR adjusted per protocol adequate clinical and parasitological responses were 95% and 100% in the AL and DP groups respectively, Mantel-Haenszel weighted odds ratio (OR) 0.22 (95% CI 0-0.68), p = 0.022. In a modified intention to treat analysis in which treatment failures day 0 and reinfections were also considered as treatment failures adequate clinical and parasitological responses were 94% and 97% (OR 0.42 [95% CI, 0.13-1.38], p = 0.15). Parasite clearance and symptom resolution were similar with both treatments.CONCLUSIONS: Both treatments achieved the WHO recommended efficacy for antimalarials about to be adopted as policy. DP was not inferior to AL for treatment of uncomplicated P. falciparum malaria in Guinea-Bissau.TRIAL REGISTRATION: ClinicalTrials.gov NTC01704508.

KW - Journal Article

U2 - 10.1371/journal.pone.0161495

DO - 10.1371/journal.pone.0161495

M3 - Journal article

C2 - 27649561

VL - 11

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 9

M1 - e0161495

ER -