Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial

Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial

BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several...

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Main Authors: Gomes, M. F., Faiz, M. A., Gyapong, J. O., Warsame, M., Agbenyega, T., Babiker, A., Baiden, F., Yunus, E. B., Binka, F., Clerk, C., Folb, P., Hassan, R., Hossain, M. A., Kimbute, O., Kitua, A., Krishna, S., Makasi, C., Mensah, N., Mrango, Z., Olliaro, P., Peto, R., Peto, T. J., Rahman, M. R., Ribeiro, I., Samad, R., White, N. J.
Format: Journal Article
Language:EN
Published: 2012
Subjects:
Rectal Administration
Adolescent
Adult
Antimalarials
Artemisinins
Child
Preschool Child
Disabled Persons
Female
Humans
Infant
Falciparum Malaria
Vivax Malaria
Male
Placebos
Rural Health Services
Suppositories
Young Adult
Online Access:http://hdl.handle.net/10986/5086
id okr-10986-5086
recordtype oai_dc
spelling okr-10986-50862021-04-23T14:02:20Z Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial Gomes, M. F. Faiz, M. A. Gyapong, J. O. Warsame, M. Agbenyega, T. Babiker, A. Baiden, F. Yunus, E. B. Binka, F. Clerk, C. Folb, P. Hassan, R. Hossain, M. A. Kimbute, O. Kitua, A. Krishna, S. Makasi, C. Mensah, N. Mrango, Z. Olliaro, P. Peto, R. Peto, T. J. Rahman, M. R. Ribeiro, I. Samad, R. White, N. J. Rectal Administration Adolescent Adult Antimalarials Artemisinins Child Preschool Child Disabled Persons Female Humans Infant Falciparum Malaria Vivax Malaria Male Placebos Rural Health Services Suppositories Young Adult BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. METHODS: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. RESULTS: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5%vs 3.0%, p=0.1). Two versus 13 (0.03%vs 0.22%, p=0.0020) were permanently disabled; total dead or disabled: 156 versus 190 (2.6%vs 3.2%, p=0.0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% CI 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0.0013). INTERPRETATION: If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. FUNDING: UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU). 2012-03-30T07:31:13Z 2012-03-30T07:31:13Z 2009-02-14 Journal Article Lancet 1474-547X (Electronic) 0140-6736 (Linking) http://hdl.handle.net/10986/5086 EN http://creativecommons.org/licenses/by-nc-nd/3.0/igo World Bank Journal Article Bangladesh Ghana Tanzania
repository_type Digital Repository
institution_category Foreign Institution
institution Digital Repositories
building World Bank Open Knowledge Repository
collection World Bank
language EN
topic Rectal Administration
Adolescent
Adult
Antimalarials
Artemisinins
Child
Preschool Child
Disabled Persons
Female
Humans
Infant
Falciparum Malaria
Vivax Malaria
Male
Placebos
Rural Health Services
Suppositories
Young Adult
spellingShingle Rectal Administration
Adolescent
Adult
Antimalarials
Artemisinins
Child
Preschool Child
Disabled Persons
Female
Humans
Infant
Falciparum Malaria
Vivax Malaria
Male
Placebos
Rural Health Services
Suppositories
Young Adult
Gomes, M. F.
Faiz, M. A.
Gyapong, J. O.
Warsame, M.
Agbenyega, T.
Babiker, A.
Baiden, F.
Yunus, E. B.
Binka, F.
Clerk, C.
Folb, P.
Hassan, R.
Hossain, M. A.
Kimbute, O.
Kitua, A.
Krishna, S.
Makasi, C.
Mensah, N.
Mrango, Z.
Olliaro, P.
Peto, R.
Peto, T. J.
Rahman, M. R.
Ribeiro, I.
Samad, R.
White, N. J.
Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial
geographic_facet Bangladesh
Ghana
Tanzania
relation http://creativecommons.org/licenses/by-nc-nd/3.0/igo
description BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. METHODS: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. RESULTS: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5%vs 3.0%, p=0.1). Two versus 13 (0.03%vs 0.22%, p=0.0020) were permanently disabled; total dead or disabled: 156 versus 190 (2.6%vs 3.2%, p=0.0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% CI 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0.0013). INTERPRETATION: If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. FUNDING: UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).
format Journal Article
author Gomes, M. F.
Faiz, M. A.
Gyapong, J. O.
Warsame, M.
Agbenyega, T.
Babiker, A.
Baiden, F.
Yunus, E. B.
Binka, F.
Clerk, C.
Folb, P.
Hassan, R.
Hossain, M. A.
Kimbute, O.
Kitua, A.
Krishna, S.
Makasi, C.
Mensah, N.
Mrango, Z.
Olliaro, P.
Peto, R.
Peto, T. J.
Rahman, M. R.
Ribeiro, I.
Samad, R.
White, N. J.
author_facet Gomes, M. F.
Faiz, M. A.
Gyapong, J. O.
Warsame, M.
Agbenyega, T.
Babiker, A.
Baiden, F.
Yunus, E. B.
Binka, F.
Clerk, C.
Folb, P.
Hassan, R.
Hossain, M. A.
Kimbute, O.
Kitua, A.
Krishna, S.
Makasi, C.
Mensah, N.
Mrango, Z.
Olliaro, P.
Peto, R.
Peto, T. J.
Rahman, M. R.
Ribeiro, I.
Samad, R.
White, N. J.
author_sort Gomes, M. F.
title Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial
title_short Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial
title_full Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial
title_fullStr Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial
title_full_unstemmed Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial
title_sort pre-referral rectal artesunate to prevent death and disability in severe malaria : a placebo-controlled trial
publishDate 2012
url http://hdl.handle.net/10986/5086
_version_ 1764393884536799232

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