Preventing Malaria During Pregnancy in Epidemic-prone Areas.

NCT ID: NCT00142207

Last Updated: 2017-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4775 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2007-01-31

Brief Summary

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.

Detailed 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.

Conditions

Malaria, Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

1

Drug: Intermittent preventive treatment:sulphadoxine-pyrimethamine

Group Type: ACTIVE_COMPARATOR

Intermittent preventive treatment:sulphadoxine-pyrimethamine

Intervention Type: DRUG

Two doses given twice during pregnancy (once in the second trimester, and once in the third trimester). Oral medication in tablet form: single daily dose given on each occasion

2

Device: Insecticide-treated mosquito bed net

Group Type: ACTIVE_COMPARATOR

Insecticide-treated mosquito bed net

Intervention Type: DEVICE

Insecticide-treated mosquito bed net

3

Combination of Drug + Device:

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

Group Type: ACTIVE_COMPARATOR

Intermittent preventive treatment:sulphadoxine-pyrimethamine

Intervention Type: DRUG

Two doses given twice during pregnancy (once in the second trimester, and once in the third trimester). Oral medication in tablet form: single daily dose given on each occasion

Insecticide-treated mosquito bed net

Intervention Type: DEVICE

Insecticide-treated mosquito bed net

Interventions

Intermittent preventive treatment:sulphadoxine-pyrimethamine

Two doses given twice during pregnancy (once in the second trimester, and once in the third trimester). Oral medication in tablet form: single daily dose given on each occasion

Intervention Type: DRUG

Insecticide-treated mosquito bed net

Insecticide-treated mosquito bed net

Intervention Type: DEVICE

Eligibility Criteria

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

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Uganda

OTHER_GOV

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Brian Greenwood

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard H Ndyomugyenyi, MBChB, PhD

Role: PRINCIPAL_INVESTIGATOR

Vector Control Division, Ministry of Health, Uganda

Sian E Clarke, PhD

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine, University of London, UK

Pascal Magnussen, MD

Role: PRINCIPAL_INVESTIGATOR

DBL - Institute for Health Research and Development, Denmark

Kristian Schultz Hansen, PhD

Role: PRINCIPAL_INVESTIGATOR

DBL - Institute for Health Research and Development, Denmark

Locations

Kabale District Health Services (antenatal clinics at selected sites)

Kabale, Kabale District, Uganda

Countries

Uganda

References

Ndyomugyenyi R, Clarke S, Chandramohan D, Twesigomwe T & Magnussen P. (2005). Epidemiology of pregnancy-associated malaria in the Ugandan highlands [abstract]. Acta Tropica, Suppl 95: S448.

Reference Type: BACKGROUND

Hansen KS, Ndyomugyenyi R, Magnussen P, Clarke SE. Cost-effectiveness analysis of three health interventions to prevent malaria in pregnancy in an area of low transmission in Uganda. Int Health. 2012 Mar;4(1):38-46. doi: 10.1016/j.inhe.2011.10.001.

Reference Type: DERIVED

PMID: 24030879 (View on PubMed)

Ndyomugyenyi R, Clarke SE, Hutchison CL, Hansen KS, Magnussen P. Efficacy of malaria prevention during pregnancy in an area of low and unstable transmission: an individually-randomised placebo-controlled trial using intermittent preventive treatment and insecticide-treated nets in the Kabale Highlands, southwestern Uganda. Trans R Soc Trop Med Hyg. 2011 Nov;105(11):607-16. doi: 10.1016/j.trstmh.2011.07.012. Epub 2011 Oct 2.

Reference Type: DERIVED

PMID: 21962292 (View on PubMed)

Other Identifiers

ITDCVG32

Identifier Type: -

Identifier Source: org_study_id