Four artemisinin-based treatments in African pregnant women with malaria

A. A. Pekyi, H. Ampromfi, M. Tinto, M. C. Traor Coulibaly, I. Tahita, V. Val, L. Mwapasa, G. Kalilani-Phiri, M. Kalanda, R. Madanitsa, T. Ravinetto, P Mutabingwa, H. Gbekor, G. Tagbor, J. Antwi, M. Menten, Y. De Crop, C. Claeys, Caroline Schurmans, K. Van Overmeir & 7 others J. P. Thriemer, U. Van Geertruyden, M. Dalessandro, Michael Nambozi, S. Mulenga, J. B B Hachizovu, J. Kabuya

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa.

METHODS: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chainreaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes.

RESULTS: The PCR-Adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin- piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-Adjusted cure rates in the intention-To-Treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin- piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-Treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine- artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups).

CONCLUSIONS: Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-Treatment prophylaxis, whereas dihydroartemisinin- piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.)

Original languageEnglish
Pages (from-to)913-927
Number of pages15
JournalNew England Journal of Medicine
Volume374
Issue number10
DOIs
Publication statusPublished - 10 Mar 2016
Externally publishedYes

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dihydroartemisinin
Mefloquine
Malaria
Pregnant Women
Safety
Therapeutics
Asthenia
Intention to Treat Analysis
Falciparum Malaria
Africa South of the Sahara
Third Pregnancy Trimester
Dizziness
Second Pregnancy Trimester
Appetite
Infection
Drug-Related Side Effects and Adverse Reactions
Treatment Failure
Nausea
Developing Countries
Vomiting

Cite this

Pekyi, A. A., Ampromfi, H., Tinto, M., Traor Coulibaly, M. C., Tahita, I., Val, V., ... Kabuya, J. (2016). Four artemisinin-based treatments in African pregnant women with malaria. New England Journal of Medicine, 374(10), 913-927. https://doi.org/10.1056/NEJMoa1508606
Pekyi, A. A. ; Ampromfi, H. ; Tinto, M. ; Traor Coulibaly, M. C. ; Tahita, I. ; Val, V. ; Mwapasa, L. ; Kalilani-Phiri, G. ; Kalanda, M. ; Madanitsa, R. ; Ravinetto, T. ; Mutabingwa, P ; Gbekor, H. ; Tagbor, G. ; Antwi, J. ; Menten, M. ; De Crop, Y. ; Claeys, C. ; Schurmans, Caroline ; Van Overmeir, K. ; Thriemer, J. P. ; Van Geertruyden, U. ; Dalessandro, M. ; Nambozi, Michael ; Mulenga, S. ; Hachizovu, J. B B ; Kabuya, J. / Four artemisinin-based treatments in African pregnant women with malaria. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 10. pp. 913-927.
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title = "Four artemisinin-based treatments in African pregnant women with malaria",
abstract = "BACKGROUND: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa. METHODS: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chainreaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes. RESULTS: The PCR-Adjusted cure rates in the per-protocol analysis were 94.8{\%} in the artemether-lumefantrine group, 98.5{\%} in the amodiaquine-artesunate group, 99.2{\%} in the dihydroartemisinin- piperaquine group, and 96.8{\%} in the mefloquine-artesunate group; the PCR-Adjusted cure rates in the intention-To-Treat analysis were 94.2{\%}, 96.9{\%}, 98.0{\%}, and 95.5{\%}, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin- piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-Treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5{\%}) than in groups that received amodiaquine-artesunate (82.3{\%}), dihydroartemisinin-piperaquine (86.9{\%}), or mefloquine-artesunate (73.8{\%}). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6{\%}) and the amodiaquine- artesunate group (48.5{\%}) than in the dihydroartemisinin-piperaquine group (20.6{\%}) and the artemether-lumefantrine group (11.5{\%}) (P<0.001 for comparison among the four groups). CONCLUSIONS: Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-Treatment prophylaxis, whereas dihydroartemisinin- piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.)",
author = "Pekyi, {A. A.} and H. Ampromfi and M. Tinto and {Traor Coulibaly}, {M. C.} and I. Tahita and V. Val and L. Mwapasa and G. Kalilani-Phiri and M. Kalanda and R. Madanitsa and T. Ravinetto and P Mutabingwa and H. Gbekor and G. Tagbor and J. Antwi and M. Menten and {De Crop}, Y. and C. Claeys and Caroline Schurmans and {Van Overmeir}, K. and Thriemer, {J. P.} and {Van Geertruyden}, U. and M. Dalessandro and Michael Nambozi and S. Mulenga and Hachizovu, {J. B B} and J. Kabuya",
note = "This article was also included in the 'Malawi Medical Journal' (RIS Id 7335352)",
year = "2016",
month = "3",
day = "10",
doi = "10.1056/NEJMoa1508606",
language = "English",
volume = "374",
pages = "913--927",
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publisher = "Massachusetts Medical Society",
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Pekyi, AA, Ampromfi, H, Tinto, M, Traor Coulibaly, MC, Tahita, I, Val, V, Mwapasa, L, Kalilani-Phiri, G, Kalanda, M, Madanitsa, R, Ravinetto, T, Mutabingwa, P, Gbekor, H, Tagbor, G, Antwi, J, Menten, M, De Crop, Y, Claeys, C, Schurmans, C, Van Overmeir, K, Thriemer, JP, Van Geertruyden, U, Dalessandro, M, Nambozi, M, Mulenga, S, Hachizovu, JBB & Kabuya, J 2016, 'Four artemisinin-based treatments in African pregnant women with malaria', New England Journal of Medicine, vol. 374, no. 10, pp. 913-927. https://doi.org/10.1056/NEJMoa1508606

Four artemisinin-based treatments in African pregnant women with malaria. / Pekyi, A. A.; Ampromfi, H.; Tinto, M.; Traor Coulibaly, M. C.; Tahita, I.; Val, V.; Mwapasa, L.; Kalilani-Phiri, G.; Kalanda, M.; Madanitsa, R.; Ravinetto, T.; Mutabingwa, P; Gbekor, H.; Tagbor, G.; Antwi, J.; Menten, M.; De Crop, Y.; Claeys, C.; Schurmans, Caroline; Van Overmeir, K.; Thriemer, J. P.; Van Geertruyden, U.; Dalessandro, M.; Nambozi, Michael; Mulenga, S.; Hachizovu, J. B B; Kabuya, J.

In: New England Journal of Medicine, Vol. 374, No. 10, 10.03.2016, p. 913-927.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Four artemisinin-based treatments in African pregnant women with malaria

AU - Pekyi, A. A.

AU - Ampromfi, H.

AU - Tinto, M.

AU - Traor Coulibaly, M. C.

AU - Tahita, I.

AU - Val, V.

AU - Mwapasa, L.

AU - Kalilani-Phiri, G.

AU - Kalanda, M.

AU - Madanitsa, R.

AU - Ravinetto, T.

AU - Mutabingwa, P

AU - Gbekor, H.

AU - Tagbor, G.

AU - Antwi, J.

AU - Menten, M.

AU - De Crop, Y.

AU - Claeys, C.

AU - Schurmans, Caroline

AU - Van Overmeir, K.

AU - Thriemer, J. P.

AU - Van Geertruyden, U.

AU - Dalessandro, M.

AU - Nambozi, Michael

AU - Mulenga, S.

AU - Hachizovu, J. B B

AU - Kabuya, J.

N1 - This article was also included in the 'Malawi Medical Journal' (RIS Id 7335352)

PY - 2016/3/10

Y1 - 2016/3/10

N2 - BACKGROUND: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa. METHODS: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chainreaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes. RESULTS: The PCR-Adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin- piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-Adjusted cure rates in the intention-To-Treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin- piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-Treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine- artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups). CONCLUSIONS: Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-Treatment prophylaxis, whereas dihydroartemisinin- piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.)

AB - BACKGROUND: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa. METHODS: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chainreaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes. RESULTS: The PCR-Adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin- piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-Adjusted cure rates in the intention-To-Treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin- piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-Treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine- artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups). CONCLUSIONS: Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-Treatment prophylaxis, whereas dihydroartemisinin- piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.)

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DO - 10.1056/NEJMoa1508606

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JO - New England Journal of Medicine

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Pekyi AA, Ampromfi H, Tinto M, Traor Coulibaly MC, Tahita I, Val V et al. Four artemisinin-based treatments in African pregnant women with malaria. New England Journal of Medicine. 2016 Mar 10;374(10):913-927. https://doi.org/10.1056/NEJMoa1508606