Clinical trial NCT00142207: Preventing Malaria During Pregnancy in Epidemic-prone Areas.
Official title: The Efficacy and Cost-effectiveness of Malaria Prevention in Pregnancy in an Area of Low and Unstable Transmission in Kabale, Uganda: Use of Intermittent Preventive Treatment and Insecticide-treated Nets.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria, Falciparum
Keywords: malaria
pregnancy
intermittent preventive treatment
insecticide-treated nets
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Uganda
First posted: 2005-09-02
Enrollment: 4775
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: mean birthweight
timeFrame: April 2004-Jan 2007
measure: prevalence of low birthweight
timeFrame: April 2004 - Jan 2007
Secondary outcomes:
measure: maternal anaemia - mean Hb at gestational age 36 weeks, prevalence of Hb<100g/L at gestational age 36 weeks
timeFrame: Feb 2003 - Jan 2007
measure: spontaneous abortions
timeFrame: Feb 2003 - Jan 2007
measure: stillbirths
timeFrame: April 2003-Jan 2007
Other outcomes:
Locations:
city: Kabale
country: Uganda
facility: Kabale District Health Services (antenatal clinics at selected sites)
state: Kabale District
Study officials:
affiliation: Vector Control Division, Ministry of Health, Uganda
name: Richard H Ndyomugyenyi, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine, University of London, UK
name: Sian E Clarke, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: DBL - Institute for Health Research and Development, Denmark
name: Pascal Magnussen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: DBL - Institute for Health Research and Development, Denmark
name: Kristian Schultz Hansen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.