See the published version of this preprint at Malaria Journal.
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Yves Daniel Compaoré
Institut de Recherche en Sciences de la Santé
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8848-2187
License:
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Background: The use of pyronaridine-artesunate (PA) has been associated with scarce transaminitis in patients. This analysis aimed to evaluate the hepatic safety profile of repeated treatment with PA versus artemether-lumefantrine (AL) in patients with consecutive uncomplicated malaria episodes in Bobo-Dioulasso, Burkina Faso.
Methods: We secondarily analyzed data from a clinical trial conducted from 2012 to 2015, in which participants with uncomplicated malaria were assigned to either PA or AL arms and followed up to 42 days. Subsequent malaria episodes within a 2-years follow up period were also treated with the same ACT initially allocated. Transaminases (AST/ALT), alkaline phosphatase (ALP), total and direct bilirubin were measured at days 0 (baseline), 3, 7, 28 and on some unscheduled days if required. The proportions of non-clinical hepatic adverse events (AEs) following first and repeated treatments with PA and AL were compared within study arms. The association of these AEs with retreatment in each arm was also determined using a logistic regression model.
Results: A total of 1379 malaria episodes were included in the intention to treat analysis with 60% of all cases occurring in the AL arm. Overall, 179 non-clinical hepatic AEs were recorded in the AL arm versus 145 in the PA arm. Elevated ALT was noted in 3.05% of treated malaria episodes, elevated AST 3.34%, elevated ALP 1.81%, and elevated total and direct bilirubin in 7.90% and 7.40% respectively. Retreated participants were less likely to experience elevated ALT and AST than first episode treated participants in both arms. One case of Hy’s law condition was recorded in a first treated participant of the PA arm. Participants from the retreatment group were 76% and 84% less likely to have elevated ALT and AST respectively in the AL arm and 68% less likely to present elevated ALT in the PA arm. In contrast, they were almost 2 times more likely to experience elevated total bilirubin in both arms.
Conclusion: Pyronaridine-artesunate and artemether-lumefantrine showed similar hepatic safety when used repeatedly in participants with uncomplicated malaria. Pyronaridine-artesunate represents therefore a suitable alternative to the current first line antimalarial drugs in use in endemic areas.
Trial Registration: Pan African Clinical Trials Registry. PACTR201105000286876
Keywords
Repeated treatment, pyronaridine-artesunate, artemether-lumefantrine, uncomplicated malaria, hepatoxicity, Hy’s law, transaminitis, hyperbilirubinemia
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View the published article at Malaria Journal.
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On 12 Jan, 2021
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Posted 07 Jan, 2021
Editor assigned
On 07 Jan, 2021
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On 07 Jan, 2021
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On 07 Jan, 2021
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Posted 05 Jan, 2021
No comments provided
Editorial decision: Minor Revision
On 01 Jan, 2021
Editor assigned
On 19 Dec, 2020
Submission checks complete
On 19 Dec, 2020
Editor invited
On 19 Dec, 2020
No comments provided
Editorial decision: Major Revision
On 30 Nov, 2020
Review #1 received
Received 29 Nov, 2020
Reviewer #1 agreed
On 05 Nov, 2020
Reviewers invited
Invitations sent on 07 Sep, 2020
Editor assigned
On 25 Aug, 2020
Submission checks complete
On 24 Aug, 2020
Editor invited
On 24 Aug, 2020
First submitted
On 20 Aug, 2020
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Subject Areas
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See the published version of this preprint at Malaria Journal.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Yves Daniel Compaoré
Institut de Recherche en Sciences de la Santé
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8848-2187
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Malaria Journal.
No community comments so far
Editor assigned
On 12 Jan, 2021
Editorial decision: Accept
On 12 Jan, 2021
Submission checks complete
On 12 Jan, 2021
Editor invited
On 12 Jan, 2021
Version (no preprint)
Posted 07 Jan, 2021
Editor assigned
On 07 Jan, 2021
Submission checks complete
On 07 Jan, 2021
Editor invited
On 07 Jan, 2021
This version was not preprinted
Version 2
Posted 05 Jan, 2021
No comments provided
Editorial decision: Minor Revision
On 01 Jan, 2021
Editor assigned
On 19 Dec, 2020
Submission checks complete
On 19 Dec, 2020
Editor invited
On 19 Dec, 2020
No comments provided
Editorial decision: Major Revision
On 30 Nov, 2020
Review #1 received
Received 29 Nov, 2020
Reviewer #1 agreed
On 05 Nov, 2020
Reviewers invited
Invitations sent on 07 Sep, 2020
Editor assigned
On 25 Aug, 2020
Submission checks complete
On 24 Aug, 2020
Editor invited
On 24 Aug, 2020
First submitted
On 20 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Malaria Journal.
Background: The use of pyronaridine-artesunate (PA) has been associated with scarce transaminitis in patients. This analysis aimed to evaluate the hepatic safety profile of repeated treatment with PA versus artemether-lumefantrine (AL) in patients with consecutive uncomplicated malaria episodes in Bobo-Dioulasso, Burkina Faso.
Methods: We secondarily analyzed data from a clinical trial conducted from 2012 to 2015, in which participants with uncomplicated malaria were assigned to either PA or AL arms and followed up to 42 days. Subsequent malaria episodes within a 2-years follow up period were also treated with the same ACT initially allocated. Transaminases (AST/ALT), alkaline phosphatase (ALP), total and direct bilirubin were measured at days 0 (baseline), 3, 7, 28 and on some unscheduled days if required. The proportions of non-clinical hepatic adverse events (AEs) following first and repeated treatments with PA and AL were compared within study arms. The association of these AEs with retreatment in each arm was also determined using a logistic regression model.
Results: A total of 1379 malaria episodes were included in the intention to treat analysis with 60% of all cases occurring in the AL arm. Overall, 179 non-clinical hepatic AEs were recorded in the AL arm versus 145 in the PA arm. Elevated ALT was noted in 3.05% of treated malaria episodes, elevated AST 3.34%, elevated ALP 1.81%, and elevated total and direct bilirubin in 7.90% and 7.40% respectively. Retreated participants were less likely to experience elevated ALT and AST than first episode treated participants in both arms. One case of Hy’s law condition was recorded in a first treated participant of the PA arm. Participants from the retreatment group were 76% and 84% less likely to have elevated ALT and AST respectively in the AL arm and 68% less likely to present elevated ALT in the PA arm. In contrast, they were almost 2 times more likely to experience elevated total bilirubin in both arms.
Conclusion: Pyronaridine-artesunate and artemether-lumefantrine showed similar hepatic safety when used repeatedly in participants with uncomplicated malaria. Pyronaridine-artesunate represents therefore a suitable alternative to the current first line antimalarial drugs in use in endemic areas.
Trial Registration: Pan African Clinical Trials Registry. PACTR201105000286876
Figure 1
Figure 2
Figure 3
Figure 4
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