Kamija Phiri 1,2 ; Michael Esan 1,2 ; Michael Boele van Hensbroek 3 ; Carole Khairallah 4 ; Brian Faragher 4 ; Feiko O ter Kuile 4 1 Community Health Department, College of Medicine, University of Malawi, Blantyre, Malawi 2 MLW Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi 3 Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands 4 Liverpool School of Tropical Medicine, Liverpool, United Kingdom Kamija Phiri Community Health Department, College of Medicine, University of Malawi
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Kamija Phiri Community Health Department, College of Medicine
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Kamija Phiri1,2; Michael Esan1,2; Michael Boele van Hensbroek3; Carole Khairallah4; Brian Faragher4; Feiko O ter Kuile4 1Community Health Department, College of Medicine, University of Malawi, Blantyre, Malawi 2MLW Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi 3Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands 4Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Kamija Phiri Community Health Department, College of Medicine, University of Malawi
To determine if 3 months of malaria chemoprevention with IPTpd reduces the incidence of deaths or readmissions due to severe anaemia or severe malaria compared to the standard single treatment course of AL on discharge
Design trial Multi-centre, double-blind, randomized, placebo controlled, superiority Primary endpoint: composite of death or re-admission due to severe
anaemia or severe malaria Study population Aged 4-59 months; admitted for severe anaemia Stable and able to switch to oral medication Completed blood transfusion & parenteral quinine
Interventions Group A. IPTpd with Coartem - given at 1 & 2 month post-discharge Group B. IPTpd with Placebo - given at 1 & 2 month post-discharge Both groups LA (Coartem at discharge)
Follow-up 0-6 month: Passive case detection; at 6 month: cross-sectional survey
1414 children recruited June 2006 - Aug 2009 By 6 months
Lost-to-FU 70 (5.0%)
Died 34 (2.4%)
Placebo (708) IPTpd (706)
Mean (SD) age in months 24.2 (13.3) 23.7 (13.5)
Male (%) 47.3 49.4
Bednet use 51.6 52.8
Cerebral malaria on admission (%) 4.4 6.4
Previous Blood transfusion (%) 12.3 11.2
Fever at randomisation (%) 10.6 12.7
Malaria smear+ at randomization (%) 32.8 35.6
HIV (%) Positive 6.6 9.3
Negative 81.2 77.6
Exposed/refusals 12.1 13.0
LA1
P1
LA
LA
LA2
P2 P= Placebo
LA= Lumefantrine-Artemether
Cox regression for repeated events (robust standard errors)
Cu
m H
aza
rd
Days
Period PE 95% CI P
1-6m
1-3m
4-6m
Intervention Extended FU
LA1
P1
LA
LA
LA2
P2 P= Placebo
LA= Lumefantrine-Artemether
Cox regression for repeated events (robust standard errors)
Cu
m H
aza
rd
Days
Period PE 95% CI P
1-6m
1-3m
4-6m
LA1
P1
LA
LA
LA2
P2 P= Placebo
LA= Lumefantrine-Artemether
Cox regression for repeated events (robust standard errors)
Cu
m H
aza
rd
Days
Period PE 95% CI P
1-6m 31 (5 to 50) 0.022
1-3m
4-6m
LA1
P1
LA
LA
LA2
P2 P= Placebo
LA= Lumefantrine-Artemether
Cox regression for repeated events (robust standard errors)
Cu
m H
aza
rd
Days
Period PE 95% CI P
1-6m 31 (5 to 50) 0.022
1-3m 41 (10 to 62) 0.014
4-6m
LA1
P1
LA
LA
LA2
P2 P= Placebo
LA= Lumefantrine-Artemether
Cox regression for repeated events (robust standard errors)
Cu
m H
aza
rd
Days
Period PE 95% CI P
1-6m 31 (5 to 50) 0.022
1-3m 41 (10 to 62) 0.014
4-6m 18 (-25 to 47) 0.355
1-3 Months (chemoprevention)
1-6 Month (+ extended follow-up)
Primary endpoint (Deaths or readmission due
severe anaemia/severe malaria)
41% (p=.01) 31% (p=.02)
All-cause hospitalization 38% (p=.01) 30% (p=.02)
Uncomplicated malaria 49% (p<.0001) 21% (p=.008)
No effect modification by age or ITNs (effective in all age groups, ITN users and non-users)
Investigators Kamija Phiri Michael Esan Michael Boele van Hensbroek Carol Khairallah Brian Faragher Feiko ter Kuile
Committee / monitors Sarah White (stats, Rx allocation) Victor Mwapasa (TSC) Neil French (TSC) Malcolm Molyneux (TSC) Elizabeth Molyneux (safety monitor) Geoffrey Targett (DSMB) Paul Milligan (DSMB) Enitan Carrol (DSMB)
Institutions College of Medicine University of Amsterdam Liverpool School of
Tropical Medicine (sponsor)
Funding NACCAP, Netherlands Gates Malaria Partnership UBS-Optimus Foundation