Sulfadoxine-pyrimethamine combinations study
| ISRCTN | ISRCTN22075368 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN22075368 |
| Secondary identifying numbers | 066681 |
- Submission date
- 06/04/2005
- Registration date
- 22/07/2005
- Last edited
- 19/10/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Malaria is a serious tropical disease caused by a parasite that is spread by mosquitoes. Antimalarial medication is used to prevent and treat malaria. However, resistance to antimalarial drugs can develop when genetic mutations allow the parasite to survive in the presence of the drug. The development of resistance is of huge public health concern. In Malawi, sulphadoxine-pyrimethamine (SDX-PYM) replaced chloroquine (CQ) in 1993 as the first-line treatment for uncomplicated malaria because of high levels of CQ resistance. However, SDX-PYM resistance is increasing. Combination treatment with two or more drugs working by different mechanisms is proposed as a means to delay the development of resistance. Combination treatments containing artemisinin (ART) are proposed as ideal for this purpose because they kill malaria parasites very rapidly and no resistance had been reported at the time of this study. There is also evidence supporting the possible use of a non-ART combination treatment as a possible alternative. Since CQ was withdrawn in 1993 there has been evidence suggesting a possible return of CQ sensitivity. Amodiaquine (AQ) in combination with SDX-PYM has been shown to be effective and well tolerated in Uganda in an area of high-level CQ resistance. This issue is of huge public health importance as combinations of CQ or AQ plus SDX-PYM would be considerably more affordable compared to ART combination treatment. The aims of this study are:
1. To compare the effectiveness of different antimalarial combination treatments
2. To compare the development of resistance when using these different treatments
3. To investigate what happens to the drugs after they are taken – their absorption and how fast they are eliminated from the body
Who can participate?
Children aged between 1 and 5 with uncomplicated malaria
What does the study involve?
Participants are randomly allocated to receive one of four treatment combinations:
1. SDX-PYM (single oral dose) and placebo (dummy drug)
2. SDX-PYM (single oral dose) + CQ (once daily for 3 days)
3. SDX-PYM (single oral dose) + Artesunate (once daily for 3 days)
4. SDX-PYM (single oral dose) + AQ (once daily for 3 days)
Participants are followed up for 42 days to assess their response to treatment and the development of resistance or side effects.
What are the possible benefits and risks of participating?
The treatments offered all contain SDX-PYM, the standard treatment for malaria in Malawi, plus an additional medicine – placebo, CQ, AQ or ART. Apart from the placebo, all of these treatments are expected to improve the cure rates for the children. Participation in the study involves additional blood tests for all the children and additional visits to the clinic. These may be an inconvenience for the children and mothers, but do provide a higher level of care than is otherwise available.
Where is the study run from?
Chileka Health Centre (Malawi)
When is the study starting and how long is it expected to run for?
September 2003 to March 2006
Who is funding the study?
Wellcome Trust (UK)
Who is the main contact?
Dr David Bell
belldavidj@gmail.com
Contact information
Scientific
Wellcome Trust Tropical Centre
Block E, Royal Infirmary Complex
University of Liverpool
70 Pembroke Place
Liverpool
L69 3GF
United Kingdom
| Phone | +44 (0)151 794 4221 |
|---|---|
| belldavidj@gmail.com |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Evaluating strategies to delay the emergence of resistance to antimalarial drugs |
| Study acronym | SP Combinations Study |
| Study hypothesis | Compared to sulfadoxine-pyrimethamine monotherapy, the addition of chloroquine or amodiaquine or artesunate results in: 1. Improved clinical and parasitological outcomes at 14, 28 and 42 days 2. Decreased selection of resistance mutations 3. Clinical failures that cannot be explained by the parasite genotype have a pharmacokinetic basis |
| Ethics approval(s) | 1. Liverpool School of Tropical Medicine, Research Ethics Commitee, 02/03/2002, ref: 01.72 2. University of Malawi, College of Medicine Research Ethics Committee, 05/08/2002, ref: P.01/02/140 |
| Condition | Uncomplicated malaria |
| Intervention | Four armed, blinded, randomised trial comparing: 1. SP (single oral dose) and placebo 2. SP (single oral dose) and chloroquine (once daily for 3 days) 3. SP (single oral dose) and amodiaquine (once daily for 3 days) 4. SP (single oral dose) and artesunate (once daily for 3 days) Total duration of follow up in study was 42 days for all participants. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Sulfadoxine-pyrimethamine, chloroquine, amodiaquine, artesunate |
| Primary outcome measure | 1. World Health Organization (WHO) treatment response endpoints on days 14, 28 and 42 2. Selection of Dihydrofolate Reductase (DHFR) and Dihydropteroate Synthetase (DHPS) resistance associated genotypes 3. Fever clearance time 4. Parasite clearance time 5. Change in haemoglobin between day zero to 14 6. Gametocyte prevalence on day seven or 14 7. Adverse events clinical and laboratory |
| Secondary outcome measures | No secondary outcome measures |
| Overall study start date | 01/09/2003 |
| Overall study end date | 15/03/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 12 Months |
| Upper age limit | 60 Months |
| Sex | Both |
| Target number of participants | 450 |
| Participant inclusion criteria | 1. Age more than or equal to 12 and less than 60 months, either sex 2. Weight more than or equal to 6 kg 3. Pure (on microscopic grounds) P. falciparum parasitaemia of 2000 to 200,000 ul 4. Written consent has been obtained from the parent or legal guardian |
| Participant exclusion criteria | 1. Severe malaria 2. Antimalarials in previous week 3. Other comcomitant infection at time of presentation 4. Allergy to sulphonamides 5. Involvement in the study in the previous 12 months |
| Recruitment start date | 01/09/2003 |
| Recruitment end date | 01/02/2006 |
Locations
Countries of recruitment
- England
- Malawi
- United Kingdom
Study participating centre
L69 3GF
United Kingdom
Sponsor information
University/education
Research Support
Senate House
Abercromby Square
Liverpool
L69 3BX
England
United Kingdom
| Website | http://www.liv.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Charity
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 13/02/2008 | Yes | No |
Editorial Notes
19/10/2016: Plain English summary added.
