Condition category
Infections and Infestations
Date applied
01/02/2006
Date assigned
01/02/2006
Last edited
23/02/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.who.int/

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)

EC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

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

foundation

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

Results - basic reporting

Publication summary

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19059639

Publication citations

  1. 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.

Additional files

Editorial Notes