Preventing Malaria During Pregnancy in Epidemic-prone Areas.

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 3

Conditions: Malaria, Falciparum

Treatments: Device: Insecticide-treated mosquito bed net; Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine

Study type: Interventional

Funder types: Other

Identifiers

NCT00142207

ITDCVG32

Details and patient eligibility

About

The purpose of this study is to compare the efficacy and cost-effectiveness of three alternative strategies for the prevention of malaria during pregnancy in an epidemic-prone area of low transmission in the East African Highlands.

The strategies being compared are:

• intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP)
• an insecticide treated net (ITN), and
• intermittent preventive treatment with SP plus an ITN

In addition to the main individually-randomised trial, outcome data was subsequently also gathered on pregnant women whose houses where sprayed with indoor residual insecticides (IRS) as part of a non-randomised district-wide control programme to compare the impact of IRS with the three intervention arms.

Full description

Susceptibility to malaria infection during pregnancy and the severity of clinical manifestation are determined by the level of pre-pregnancy immunity, which depends on intensity and stability of malaria transmission. Most intervention trials to prevent malaria during pregnancy have been conducted in areas of intense transmission. The results of trials conducted in high-transmission areas may not be applicable to low transmission areas, where malaria is less frequent but the risk of spontaneous abortion and stillbirth is very high in women of all parities due to lack of sufficient malaria immunity. Routine chemoprophylaxis is generally not recommended in areas of unstable malaria transmission. However, intermittent treatment with an effective anti-malarial drug may be beneficial, especially during periods of malaria transmission. Little work has been carried out amongst pregnant women living in areas of low and unstable transmission in Africa. No data are available on the cost-effectiveness of malaria control in low transmission settings.

This study will compare the efficacy and cost effectiveness of three preventive strategies for the control of malaria during pregnancy in low-transmission settings. The study is located in Kabale district, a highland area in SW Uganda.

Women attending antenatal care are randomised to receive either:

• intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP)
• an insecticide treated net (ITN), or
• intermittent preventive treatment with SP and an ITN. It is hypothesized that when combined with IPT-SP, the additional impact of ITNs by reducing exposure may be greatest where the intensity of transmission is low.

In addition to the main individually-randomised trial, outcome data was subsequently also gathered on pregnant women whose houses where sprayed with indoor residual insecticides (IRS) as part of a non-randomised district-wide control programme to compare the impact of IRS with the three intervention arms.

The study aims to identify the most effective intervention strategies suited to areas characterised by low and unstable transmission. Research findings should be applicable to other hypoendemic areas of the East African highlands.

Enrollment: 4,775 patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pregnant women whose pregnancies are at <27 weeks gestation at first antenatal booking
• Permanent resident in study area
• Informed consent

Exclusion criteria

• Late presentation: pregnancies more than 26 weeks gestation at first antenatal booking
• Severe anaemia (Hb<70g/L) on enrolment
• Previous reaction to a sulfa-drug (e.g. sulphadoxine-pyrimethamine, septrin)
• History of severe skin reaction to any drug
• Current (or history) of severe disease (e.g. hepatitis, jaundice, TB, AIDS)

Withdrawal Criteria:

• Withdrawal of consent
• Women developing severe anaemia (Hb<70g/L)during pregnancy

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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4,775 participants in 3 patient groups

1

Active Comparator group

Description:

Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine

Treatment:

Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine

2

Active Comparator group

Description:

Device: Insecticide-treated mosquito bed net

Treatment:

Device: Insecticide-treated mosquito bed net

3

Active Comparator group

Description:

Combination of Drug + Device: Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine Device: Insecticide-treated mosquito bed net

Treatment:

Device: Insecticide-treated mosquito bed net

Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine