Contact information
Type
Scientific
Primary contact
Dr Melba Gomes
ORCID ID
Contact details
20
Avenue Appia
Geneva-27
CH 1211
Switzerland
+41 (0)22 791 3813
gomesm@who.int
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
The objective has been to establish whether, in patients with acute malaria who cannot take medication by mouth, rectal artesunate plus referral differs from rectal placebo plus referral in terms of death or permanent disability.
Ethics approval
Ethics approval received on the 8th July 1998.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Malaria
Intervention
The sample size determination in the protocol specified that a total of 10,000 non per os patients would need to be randomised in order to detect a reduction of mortality from 5% to 3%.
Individual patients will be randomised to receive either AS suppository (intervention group) or placebo (comparator group). Patients in both groups will then be referred immediately to the nearest hospital/health centre where all supportive treatment will be provided.
Intervention type
Drug
Phase
Not Specified
Drug names
Artesunate (AS)
Primary outcome measure
1. Number of relevant deaths in the intervention and control arm assessed 7 - 30 days after enrolment (relevant defined as malaria positive patients in whom the death was probably/definitely preventable by the intervention)
2. Number of individuals with serious neurological disability in the intervention and control arms assessed at 7 - 30 days following enrolment in the study. Neurological disability defined as the development of new problems with feeding, walking, talking, sitting, sight, hearing, playing, balance and behaviour
Secondary outcome measures
1. Number of deaths in the intervention and control arm assessed 7 - 30 days following enrolment in the study
2. Number of cases of neurological disability in the intervention and control arms assessed at 7 - 30 days following enrolment in the study
3. Number of cases of neurological disability in malaria smear positive patients in the intervention and control arms assessed at 7 - 30 days following enrolment in the study
4. Number of cases of neurological disability in children in the intervention and control arms assessed at 7 - 30 days following enrolment in the study
5. Number of cases of neurological disability in pregnant women in the intervention and control arms assessed at 7 - 30 days following enrolment in the study
6. Number of deaths and neurological sequelae in the intervention and control arm in malaria smear positive patients who survived at least 8 hours but died before 7 days after enrolment in the study
Overall trial start date
08/07/1998
Overall trial end date
08/07/2000
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Children above crawling age and adults of any age group
2. Clinical diagnosis of probable P. falciparum malaria (fever, or history of fever without any other obvious cause of fever). Clinical features must include fever or history of fever and at least one of the following:
2.1. Unable to take food, drink or suck
2.2. Prostration: inability to sit, stand or walk unaided
2.3. Any abnormal level of consciousness i.e. from abnormal behavior, obtunded (limited response to painful stimulus), to coma (unconsciousness with absent verbal response and non-specific or absent motor response)
2.4. Fits or history of fits (defined as more than one fit in the previous 24 hours)
3. Consent by patient or parent/guardian if patient is less than 18
4. Community informed consent - at the start of the study in that area, community consent to the project would have been obtained
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
In this trial, it is not the number of patients recruited but the number of deaths that determine the statistical power of such a trial.
Participant exclusion criteria
1. Afebrile (history/examination)
2. Unwillingness to sign (or parental signature) informed consent for study participation
3. Ability to take oral medication
4. Diarrhoea (at least two loose bowel movements in the previous two hours)
N.B. Pregnant or breast-feeding women will not be excluded from the study. Status of pregnancy in female will be noted in the Case Record Form (CRF).
Recruitment start date
08/07/1998
Recruitment end date
08/07/2000
Locations
Countries of recruitment
Bangladesh
Trial participating centre
20, Avenue Appia
Geneva-27
CH 1211
Switzerland
Sponsor information
Organisation
UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR)
Sponsor details
20
Avenue Appia
Geneva-27
CH 1211
Switzerland
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
Sources of funding:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
United Nations Children's Fund (UNICEF)/United Nations Development Programme (UNDP)/World Bank/World Health Organization (WHO) - Special Programme for Research and Training in Tropical Diseases (TDR)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
European Commission (Belgium)
Alternative name(s)
European Union, EC, EU
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Funder name
WHO Global Malaria Programme
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
US Agency for International Development (USAID) (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Irish Aid (Ireland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Karolinska Institutet (Sweden)
Alternative name(s)
Karolinska Institute, KI
Funding Body Type
government organisation
Funding Body Subtype
government non-federal
Location
Sweden
Funder name
Sall Family Foundation (USA)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
Trusts, charities, foundations (both publically funded and privately funded)
Location
United States of America
Funder name
University of Oxford Clinical Trial Service Unit (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19059639
Publication citations
-
Results
Gomes MF, Faiz MA, Gyapong JO, Warsame M, Agbenyega T, Babiker A, Baiden F, Yunus EB, Binka F, Clerk C, Folb P, Hassan R, Hossain MA, Kimbute O, Kitua A, Krishna S, Makasi C, Mensah N, Mrango Z, Olliaro P, Peto R, Peto TJ, Rahman MR, Ribeiro I, Samad R, White NJ, , Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial., Lancet, 2009, 373, 9663, 557-566, doi: 10.1016/S0140-6736(08)61734-1.