| Moussa Djimde, Japhet Kabalu Tshiongo, Hypolite Mavoko Muhindo, Halidou Tinto, Esperanca Sevene, Maminata Traore, Anifa Vala, Salesio MacUacua, Berenger Kabore, Edgard Diniba Dabira, Annette Erhart, Hamadoun Diakite, Mohamed Keita, Mireia Piqueras, Raquel González, Clara Menendez, Thomas P. C. Dorlo, Issaka Sagara, Petra Mens, Henk Schallig, Umberto D'Alessandro, Kassoum Kayentao Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial Journal Article In: BMJ open, vol. 13, iss. 10, 2023, ISSN: 2044-6055. @article{Djimde2023,
title = {Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial},
author = {Moussa Djimde and Japhet Kabalu Tshiongo and Hypolite Mavoko Muhindo and Halidou Tinto and Esperanca Sevene and Maminata Traore and Anifa Vala and Salesio MacUacua and Berenger Kabore and Edgard Diniba Dabira and Annette Erhart and Hamadoun Diakite and Mohamed Keita and Mireia Piqueras and Raquel Gonz\'{a}lez and Clara Menendez and Thomas P. C. Dorlo and Issaka Sagara and Petra Mens and Henk Schallig and Umberto D'Alessandro and Kassoum Kayentao},
url = {https://pubmed.ncbi.nlm.nih.gov/37813539/},
doi = {10.1136/BMJOPEN-2022-065295},
issn = {2044-6055},
year = {2023},
date = {2023-01-01},
journal = {BMJ open},
volume = {13},
issue = {10},
publisher = {BMJ Open},
abstract = {Introduction Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. Methods and analysis A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. Ethics and dissemination This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. Trial registration number PACTR202011812241529.},
keywords = {Antimalarials* / adverse effects, Artemether, Artemether / therapeutic use, Artemisinins* / adverse effects, Clinical Trial Protocol, Clinical Trials, doi:10.1136/bmjopen-2022-065295, Drug Combinations, Falciparum* / drug therapy, Female, Humans, Infant, Japhet Kabalu Tshiongo, Kassoum Kayentao, Lumefantrine Drug Combination / therapeutic use, Malaria, Malaria* / drug therapy, MEDLINE, Moussa Djimde, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase III as Topic, PMC10565244, pmid:37813539, Pregnancy, Pregnant Women, PubMed Abstract, Randomized Controlled Trials as Topic, Research Support, Sub-Saharan African People, Treatment Outcome},
pubstate = {published},
tppubtype = {article}
}
Introduction Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. Methods and analysis A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. Ethics and dissemination This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. Trial registration number PACTR202011812241529. |
 | Adama Gansané, Leah F Moriarty, Didier Ménard, Isidore Yerbanga, Esperance Ouedraogo, Paul Sondo, Rene Kinda, Casimir Tarama, Edwige Soulama, Madou Tapsoba, David Kangoye, Cheick Said Compaore, Ousmane Badolo, Blami Dao, Samuel Tchwenko, Halidou Tinto, Innocent Valea Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018 Journal Article In: Malar. J., vol. 20, no. 1, pp. 48, 2021, ISSN: 1475-2875. @article{Gansane2021-yh,
title = {Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018},
author = {Adama Gansan\'{e} and Leah F Moriarty and Didier M\'{e}nard and Isidore Yerbanga and Esperance Ouedraogo and Paul Sondo and Rene Kinda and Casimir Tarama and Edwige Soulama and Madou Tapsoba and David Kangoye and Cheick Said Compaore and Ousmane Badolo and Blami Dao and Samuel Tchwenko and Halidou Tinto and Innocent Valea},
doi = {10.1186/s12936-021-03585-6},
issn = {1475-2875},
year = {2021},
date = {2021-01-19},
urldate = {2021-01-01},
journal = {Malar. J.},
volume = {20},
number = {1},
pages = {48},
publisher = {Springer Science and Business Media LLC},
abstract = {BACKGROUND: The World Health Organization recommends regularly
assessing the efficacy of artemisinin-based combination therapy
(ACT), which is a critical tool in the fight against malaria.
This study evaluated the efficacy of two artemisinin-based
combinations recommended to treat uncomplicated Plasmodium
falciparum malaria in Burkina Faso in three sites: Niangoloko,
Nanoro, and Gourcy. METHODS: This was a two-arm randomized
control trial of the efficacy of artemether-lumefantrine (AL)
and dihydroartemisinin-piperaquine (DP). Children aged 6-59
months old were monitored for 42 days. The primary outcomes of
the study were uncorrected and PCR-corrected efficacies to day
28 for AL and 42 for DP. Molecular markers of resistance to
artemisinin derivatives and partner drugs were also analysed.
RESULTS: Of 720 children enrolled, 672 reached study endpoints
at day 28, 333 in the AL arm and 339 in the DP arm.
PCR-corrected 28-day per protocol efficacy in the AL arm was
74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92%
(84-96%) in Niangoloko. The PCR-corrected 42-day per protocol
efficacy in the DP arm was 84% (75-89%) in Gourcy, 89%
(81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13
mutation previously associated with artemisinin-resistance was
observed. No statistically significant association was found
between treatment outcome and presence of the 86Y mutation in
the Pfmdr1 gene. There was also no association observed between
treatment outcome and Pfpm2 or Pfmdr1 copy number variation.
CONCLUSION: The results of this study indicate evidence of
inadequate efficacy of AL at day 28 and DP at day 42 in the same
two sites. A change of first-line ACT may be warranted in
Burkina Faso. Trial Registry Pan African Clinical Trial Registry
Identifier: PACTR201708002499311. Date of registration: 8/3/2017
https://pactr.samrc.ac.za/Search.aspx.},
keywords = {Antimalarial, Antimalarials/pharmacology, Artemether, Artemether-lumefantrine, Artemisinins/pharmacology, Burkina Faso, Child, Dihydroartemisinin-piperaquine, Drug Resistance, Efficacy, Falciparum/drug therapy, Female, Lumefantrine Drug Combination/pharmacology, Malaria, Male, Plasmodium falciparum, Preschool, Quinolines/pharmacology},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The World Health Organization recommends regularly
assessing the efficacy of artemisinin-based combination therapy
(ACT), which is a critical tool in the fight against malaria.
This study evaluated the efficacy of two artemisinin-based
combinations recommended to treat uncomplicated Plasmodium
falciparum malaria in Burkina Faso in three sites: Niangoloko,
Nanoro, and Gourcy. METHODS: This was a two-arm randomized
control trial of the efficacy of artemether-lumefantrine (AL)
and dihydroartemisinin-piperaquine (DP). Children aged 6-59
months old were monitored for 42 days. The primary outcomes of
the study were uncorrected and PCR-corrected efficacies to day
28 for AL and 42 for DP. Molecular markers of resistance to
artemisinin derivatives and partner drugs were also analysed.
RESULTS: Of 720 children enrolled, 672 reached study endpoints
at day 28, 333 in the AL arm and 339 in the DP arm.
PCR-corrected 28-day per protocol efficacy in the AL arm was
74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92%
(84-96%) in Niangoloko. The PCR-corrected 42-day per protocol
efficacy in the DP arm was 84% (75-89%) in Gourcy, 89%
(81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13
mutation previously associated with artemisinin-resistance was
observed. No statistically significant association was found
between treatment outcome and presence of the 86Y mutation in
the Pfmdr1 gene. There was also no association observed between
treatment outcome and Pfpm2 or Pfmdr1 copy number variation.
CONCLUSION: The results of this study indicate evidence of
inadequate efficacy of AL at day 28 and DP at day 42 in the same
two sites. A change of first-line ACT may be warranted in
Burkina Faso. Trial Registry Pan African Clinical Trial Registry
Identifier: PACTR201708002499311. Date of registration: 8/3/2017
https://pactr.samrc.ac.za/Search.aspx. |
