Hepatic safety of repeated treatment with pyronaridine-artesunate (PA) versus artemether-lumefantrine (AL) in patients with uncomplicated malaria: A secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso

Abstract BackgroundThe 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.MethodsWe secondarily analyzed data from a clinical trial conducted from 2012 to 2015, in which patients 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 models.ResultsA 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 with 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. Patients 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.ConclusionPyronaridine-artesunate and artemether-lumefantrine showed similar hepatic safety when used repeatedly in patients with uncomplicated malaria. Pyronaridine-artesunate represents therefore a suitable alternative to the current first line antimalarial drugs in use in endemic areas.Trial RegistrationPan African Clinical Trials Registry. PACTR201105000286876

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Hepatic safety of repeated treatment with pyronaridine‐artesunate versus artemether–lumefantrine in patients with uncomplicated malaria: a secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso

Malaria Journal ◽

10.1186/s12936-021-03593-6 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yves Daniel Compaoré ◽

Issaka Zongo ◽

Anyirékun F. Somé ◽

Nouhoun Barry ◽

Frederick Nikiéma ◽

...

Keyword(s):

Burkina Faso ◽

Uncomplicated Malaria ◽

Secondary Analysis ◽

Direct Bilirubin ◽

First Episode ◽

Repeated Treatment ◽

Suitable Alternative ◽

Intention To Treat ◽

Bobo Dioulasso ◽

Malaria Episodes

Abstract 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 This study analysed 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. Conclusions 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 anti-malarial drugs in use in endemic areas. Trial registration Pan African Clinical Trials Registry. PACTR201105000286876

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Hepatic safety of repeated treatment with pyronaridine-artesunate versus artemether-lumefantrine in patients with uncomplicated malaria: a secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso

10.21203/rs.3.rs-63636/v3 ◽

2021 ◽

Author(s):

Yves Daniel Compaoré ◽

Issaka Zongo ◽

Anyirékun F. Somé ◽

Nouhoun Barry ◽

Frederick Nikiema ◽

...

Keyword(s):

Burkina Faso ◽

Uncomplicated Malaria ◽

Secondary Analysis ◽

Direct Bilirubin ◽

First Episode ◽

Repeated Treatment ◽

Suitable Alternative ◽

Intention To Treat ◽

Bobo Dioulasso ◽

Malaria Episodes

Abstract BackgroundThe 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. MethodsThis study analysed 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. ResultsA 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.ConclusionPyronaridine-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 anti-malarial drugs in use in endemic areas.

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Hepatic safety of repeated treatment with pyronaridine-artesunate (PA) versus artemether-lumefantrine (AL) in patients with uncomplicated malaria: A secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso.

10.21203/rs.3.rs-63636/v2 ◽

2021 ◽

Author(s):

Yves Daniel Compaoré ◽

Issaka Zongo ◽

Anyirékun F. Somé ◽

Nouhoun Barry ◽

Frederick Nikiema ◽

...

Keyword(s):

Burkina Faso ◽

Uncomplicated Malaria ◽

Secondary Analysis ◽

Direct Bilirubin ◽

First Episode ◽

Repeated Treatment ◽

Suitable Alternative ◽

Intention To Treat ◽

Bobo Dioulasso ◽

Malaria Episodes

Abstract 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

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RANDOMIZED TRIAL TO ASSESS EFFECT OF REPEATED TREATMENT OF DHA-PQ AND AL ON QTC INTERVAL IN PATIENTS PRESENTING WITH UNCOMPLICATED MALARIA IN BOBO-DIOULASSO, BURKINA FASO

BMJ Global Health ◽

10.1136/bmjgh-2016-000260.34 ◽

2017 ◽

Vol 2 (Suppl 2) ◽

pp. A14.2-A14

Author(s):

Naomie Kabore ◽

Nouhoun Barry ◽

Zachari Kabre ◽

Karidia Werme ◽

Aminata Fofana ◽

...

Keyword(s):

Burkina Faso ◽

Randomized Trial ◽

Uncomplicated Malaria ◽

Repeated Treatment ◽

Qtc Interval ◽

Bobo Dioulasso

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Dihydroartemisinin-piperaquine for the routine treatment of uncomplicated malaria in Northern Ghana

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20200200 ◽

2020 ◽

Vol 7 (1) ◽

pp. 1

Author(s):

Abraham R. Oduro ◽

Samuel Chatio ◽

Emmanuel Ayamba ◽

Thomas Anyorigiya ◽

Fred Binka ◽

...

Keyword(s):

Uncomplicated Malaria ◽

Haemoglobin Concentration ◽

Febrile Illness ◽

Northern Ghana ◽

First Line ◽

Intention To Treat ◽

Health Delivery ◽

Baseline Temperature ◽

Concentration Changes

Background: Dihydroartemisinin-piperaquine is a first line treatment for uncomplicated malaria in Ghana. A facility-based study was undertaken to examine the effectiveness of the treatment in the routine health care system.Methods: The study was undertaken at the Navrongo demographic surveillance area. Patients presenting with acute febrile illness were enrolled after informed consented and confirmation by microscopy. Patients were randomized into supervised group who received treatment under direct observation and unsupervised group which had only the first treatment given under supervision. Treatment was according to bodyweight and 42 days follow-up was undertaken.Results: A total of 194 patients were enrolled; 54.1% were females and 51% had supervised treatment. The median age and weight were 6.7 years and 20.0 kg respectively. Mean baseline temperature, haemoglobin concentration and parasite density were, 37.6 oC, 11.1 g/dl and 11,098 parasites per microliter of blood respectively. Study completion rate was 93.3%, day 42 polymerase chain reaction-unadjusted adequate clinical and parasitological responses rate (ACPR) was 93.4% by evaluable and 87.1 % by intention-to-treat (ITT). The day 42 ACPR by evaluable was 92.3% in the supervised arm compared to 94.4% in the unsupervised arm. The day 42 ACPR by ITT was 85.7% in the supervised and 88.5% in the unsupervised arms. The fever resolution and haemoglobin concentration changes for the two arms were similar.Conclusions: The results show that dihydroartemisinin-piperaquine is effective and good first-line antimalarial in the routine health delivery system.

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Impact of first episode psychosis treatment on heavy cannabis use: Secondary analysis on RAISE-ETP study

Schizophrenia Research ◽

10.1016/j.schres.2019.07.014 ◽

2019 ◽

Vol 211 ◽

pp. 86-87 ◽

Cited By ~ 5

Author(s):

Karl C. Alcover ◽

Oladunni Oluwoye ◽

Liat Kriegel ◽

Sterling McPherson ◽

Michael G. McDonell

Keyword(s):

Secondary Analysis ◽

First Episode Psychosis ◽

Cannabis Use ◽

First Episode ◽

Episode Psychosis

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Lived experiences of negative symptoms in first-episode psychosis: A qualitative secondary analysis

Early Intervention in Psychiatry ◽

10.1111/eip.12558 ◽

2018 ◽

Vol 13 (4) ◽

pp. 773-779 ◽

Cited By ~ 1

Author(s):

Brioney Gee ◽

Jo Hodgekins ◽

Anna Lavis ◽

Caitlin Notley ◽

Max Birchwood ◽

...

Keyword(s):

Lived Experiences ◽

Negative Symptoms ◽

Secondary Analysis ◽

First Episode Psychosis ◽

First Episode ◽

Episode Psychosis ◽

Qualitative Secondary Analysis

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Graduated compression stockings to treat acute leg pain associated with proximal DVT

Thrombosis and Haemostasis ◽

10.1160/th14-05-0430 ◽

2014 ◽

Vol 112 (12) ◽

pp. 1137-1141 ◽

Cited By ~ 32

Author(s):

Stan Shapiro ◽

Thierry Ducruet ◽

Philip Wells ◽

Marc Rodger ◽

Michael Kovacs ◽

...

Keyword(s):

Rating Scale ◽

Controlled Trial ◽

Venous Blood ◽

Secondary Analysis ◽

Pain Severity ◽

Leg Pain ◽

First Episode ◽

Venous Blood Flow ◽

Compression Stockings ◽

Anatomical Extent

SummaryAcute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30–40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

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Pilot study of a ketogenic diet in relapsing-remitting MS

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000565 ◽

2019 ◽

Vol 6 (4) ◽

pp. e565 ◽

Cited By ~ 22

Author(s):

J. Nicholas Brenton ◽

Brenda Banwell ◽

A.G. Christina Bergqvist ◽

Diana Lehner-Gulotta ◽

Lauren Gampper ◽

...

Keyword(s):

Ketogenic Diet ◽

Brain Mri ◽

Secondary Analysis ◽

Primary Data ◽

Control Group ◽

Open Label ◽

Modified Atkins Diet ◽

Intention To Treat ◽

Primary Data Analysis ◽

Total Fat

ObjectiveTo assess the safety and tolerability of a modified Atkins diet (KDMAD), a type of ketogenic diet (KD), in subjects with relapsing MS while exploring potential benefits of KDs in MS.MethodsTwenty subjects with relapsing MS enrolled into a 6-month, single-arm, open-label study of the KDMAD. Adherence to KDMAD was objectively monitored by daily urine ketone testing. Fatigue and depression scores and fasting adipokines were obtained at baseline and on diet. Brain MRI was obtained at baseline and 6 months. Intention to treat was used for primary data analysis, and a per-protocol approach was used for secondary analysis.ResultsNo subject experienced worsening disease on diet. Nineteen subjects (95%) adhered to KDMAD for 3 months and 15 (75%) adhered for 6 months. Anthropometric improvements were noted on KDMAD, with reductions in body mass index and total fat mass (p < 0.0001). Fatigue (p = 0.002) and depression scores (p = 0.003) were improved. Serologic leptin was significantly lower at 3 months (p < 0.0001) on diet.ConclusionsKDMAD is safe, feasible to study, and well tolerated in subjects with relapsing MS. KDMAD improves fatigue and depression while also promoting weight loss and reducing serologic proinflammatory adipokines.Classification of evidenceThe study is rated Class IV because of the absence of a non-KD control group.

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