Three Alternative Drug Regimens for Malaria Seasonal Preventive Treatment in Senegal

NCT ID: NCT00529620

Last Updated: 2010-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1833 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2007-12-31

Brief Summary

The purpose of this trial is to compare the acceptability, efficacy and safety of three alternative drug regimens for use for seasonal Intermittent Preventive Treatment to prevent malaria in children. Children aged 2 months to 5 years will be randomized to receive IPT with one of three regimens during the transmission season: sulfadoxine-pyrimethamine (SP) plus amodiaquine, show to be highly effective for IPT in a recent trial; SP plus piperaquine, used for malaria prophylaxis in China for many years; or Duocotexcin (a combination of piperaquine with an artemisinin).

Detailed Description

In areas of seasonal malaria transmission the burden of severe disease and mortality due to malaria is mainly among children under 5 years of age. Intermittent preventive treatment (IPT) with antimalarial drugs given to all children once a month during the transmission season is a promising new strategy for malaria prevention. Seasonal IPT with sulfadoxine-pyrimethamine (SP) and one dose of artesunate resulted in a 90% reduction in incidence of clinical malaria in a recent trial in Senegal (Cisse et al., Lancet 2006). An important consideration is the possible impact of seasonal IPT on the emergence and spread of drug resistant parasite genotypes, the choice of drug regimen is therefore critical. A second trial in Senegal showed that a combination of two non-artemisinin drugs with relatively long half lives (SP and amodiaquine (AQ) over three days) was more effective than SP with artesunate and more effective than AQ with artesunate, in preventing malaria; and very few children developed parasitaemia, so that the potential for drug resistant genotypes to emerge and spread was low. Although SP+AQ was more efficacious than the artemisinin-containing regimens tested, it was associated with a higher frequency of adverse events, especially vomiting, and AQ has a bitter unpleasant taste, and therefore we have concerns about the acceptability of AQ for widespread use for IPT. It is important to select a drug regimen that is not only effective but safe and acceptable to the community. Each treatment is a 3-dose regimen over 3 days, the first dose will be supervised and the other 2 doses given by the mother or carer. One month after each treatment round, children will be visited at home to check for malaria symptoms, children with fever or a history of fever in the last 48 hours will be asked to give a finger prick blood sample for malaria diagnosis. One month after the last treatment all children will be asked to give a finger prick blood sample for parasitology and haemoglobin, axillary temperature will be measured. The child's carer will be interviewed about compliance and adverse events. The endpoints will be the cumulative incidence of malaria, the proportion of children experiencing moderate and severe adverse events, compliance with and acceptability of the regimen, the prevalence of parasitaemia, and the proportion of children carrying parasite genotypes associated with resistance to sulfadoxine or pyrimethamine at the end of the transmission season. Since acceptability is difficult to assess in the formal setting of a trial, and because the method of delivery may affect compliance and acceptability, drug treatments will be delivered by community workers replicating the conditions under IPT would be delivered routinely in Senegal. Treatments will be administered at home by local community workers, each worker covering a circuit of approximately 60-80 children. The community worker circuit will be the unit of randomization, for simplicity in the field to minimise allocation errors, and to avoid contamination due to sharing of tablets within a household.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

sulfalene pyrimethamine plus amodiaquine

Group Type: ACTIVE_COMPARATOR

sulfalene-pyrimethamine plus amodiaquine

Intervention Type: DRUG

Monthly treatments during the malaria transmission season

2

dihydroartemisinin piperaquine

Group Type: ACTIVE_COMPARATOR

dihydroartemisinin plus piperaquine

Intervention Type: DRUG

Monthly treatments during the transmission season

3

sulfadoxine-pyrimethamine plus piperaquine

Group Type: ACTIVE_COMPARATOR

sulfadoxine pyrimethamine plus piperaquine

Intervention Type: DRUG

Monthly treatments during the malaria transmission season

Interventions

sulfalene-pyrimethamine plus amodiaquine

Monthly treatments during the malaria transmission season

Intervention Type: DRUG

dihydroartemisinin plus piperaquine

Monthly treatments during the transmission season

Intervention Type: DRUG

sulfadoxine pyrimethamine plus piperaquine

Monthly treatments during the malaria transmission season

Intervention Type: DRUG

Other Intervention Names

Dualkin; Duo cotexcin; sulfadoxine pyrimethamine; piperaquine phosphate

Eligibility Criteria

Inclusion Criteria

• age 2 to 59 months in September 2007

Exclusion Criteria

• history of allergy to study drugs

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cheikh Anta Diop University, Senegal

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

University of Dakar

Principal Investigators

Badara Cisse, PhD

Role: PRINCIPAL_INVESTIGATOR

Universite Cheikh Anta Diop

Paul J Milligan, PhD

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine

Locations

Departement de Parasitologie et Mycologie, Universite Cheikh Anta Diop

Dakar, , Senegal

Countries

Senegal

References

Cisse B, Cairns M, Faye E, NDiaye O, Faye B, Cames C, Cheng Y, NDiaye M, Lo AC, Simondon K, Trape JF, Faye O, NDiaye JL, Gaye O, Greenwood B, Milligan P. Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children. PLoS One. 2009 Sep 28;4(9):e7164. doi: 10.1371/journal.pone.0007164.

Reference Type: DERIVED

PMID: 19784374 (View on PubMed)

Other Identifiers

5184

Identifier Type: -

Identifier Source: org_study_id