Kilimanjaro IPTi Drug Options Trial

Summary

Malaria and anaemia are major causes of morbidity and mortality in children in sub-Saharan Africa. Administration of three courses of sulfadoxine/pyrimethamine (SP) as intermittent preventive treatment (IPTi) to infants when they receive EPI vaccines reduced the incidence of malaria and anaemia in infants in an area with low SP resistance, low transmission pressure and high bednet use. However, it is not clear whether this observation can be generalised to areas with high transmission and high SP resistance. The mechanism of the protective effect of IPTi is unclear. There is an urgent need to identify other anti-malarial drugs that could be used for IPTi instead of SP.

This study objectives are:

1. Identification of a drug that could be used safely and effectively for IPTi instead of SP in areas, such as north eastern Tanzania, where there is a high level of resistance to SP and amodiaquine.
2. Determination of whether a short acting antimalarial drug (Lapdap) is as effective as a long acting drug (mefloquine) when used for IPTi.
3. Investigation of the effect of the intensity of transmission on the requirements for a long or short acting drug for IPTi.
4. Assessment of the effect of IPTi on the development of clinical immunity in children in low and high transmission areas.

A randomised trial with four treatment regimes is proposed which will be conducted in two different transmission settings. The four treatment regimens are as follows: (1) placebo; (2) mefloquine; (3) Lapdap; (4) SP. All medications will be given at the time of immunisation with DPT/polio 2, DPT/polio 3, and measles vaccines. The study will involve 1280 infants in a high endemic area and 2440 infants in a low endemic area, in Tanzania.The primary outcome is the incidence of clinical malaria.

Conditions

• Malaria

Interventions

DRUG

sulphadoxine-pyrimethamine

DRUG

mefloquine

DRUG

Chlorproguanil-dapsone

DRUG

Placebo

Placebo

DRUG

Sulphadoxine-pryrimethamine

IPTi doses 1 and 2, at ages 2 and 3 months, sulphadoxine 250mg, pyrimethamine 12.5mg IPTi doses 3, at 9 months of age, sulphadoxine 500mg, pyrimethamine 25mg

DRUG

IPTi mefloquine

IPTi doses 1 \& 2 at ages 2 \& 3 months, mefloquine 125mg IPTi dose 3 at 9 months, mefloquine 250mg

DRUG

Chlorproguanil dapsone

IPTi doses 1 and 2 at ages 2 and 3 months, doses 15mg chlorproguanil and 18.75mg dapsone IPTi dose 3 at 9 months of age, doses 22.5mg chlorproguanil and 28.13mg dapsone

Sponsors & Collaborators

• University of Copenhagen

  collaborator OTHER

• National Institute for Medical Research, Tanzania

  collaborator OTHER_GOV

• Kilimanjaro Christian Medical Centre, Tanzania

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  lead OTHER

Principal Investigators

• Roly Gosling, MBChB, MRCP · London School of Hygiene and Tropical Medicine

• Daniel Chandramohan, MBBS,PhD · London School of Hygiene and Tropical Medicine

• Brian Greenwood, FRCP, FRS · London School of Hygiene and Tropical Medicine

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

QUADRUPLE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Months

Max Age

24 Months

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2005-01-31

Primary Completion

2008-04-30

Completion

2008-06-30

Countries

• Tanzania

Study Locations