The purpose of this study is to examine if treatment of pregnant Malawian women with repeated doses of sulfadoxine, pyrimethamine and azithromycin antibiotics will prevent preterm deliveries and result in other health benefits both to the mother and the foetus / newborn.

Condition	Intervention	Phase
Malaria in pregnancy Sexually Transmitted Diseases Preterm Birth	Drug: sulfadoxine-pyrimethamine treatment twice during pregnancy  Drug: Sulfadoxine-pyrimethamine at 4-week intervals  Drug: Sulfadoxine-pyrimethamine every 4-w + azithromycin twice	Phase III

Further Study Details: 

Primary Outcomes: Proportion of preterm births; Number of serious and any adverse events
Secondary Outcomes: Percentage of low birth weight babies; Mean birth weight; Mean duration of gestation; Percentage of low chest circumference at birth; Percentage of low chest or head circumference at birth; Incidence of moderate underweight during infancy; Perinatal, neonatal and infant mortality; Mean maternal blood haemoglobin concentration at each antenatal visit and at 1, 3, and 6 months after delivery; Percentage of women with mild, moderate or severe anaemia at every antenatal visit and at 1, 3, and 6 months after delivery; Percentage of women with peripheral blood malaria parasitaemia and mean parasite density at enrolment, at 32 gestational weeks and at delivery; Percentage of women with cord blood and placental malaria parasitaemia at delivery; Maternal weight gain during pregnancy; Mean number of maternal illness days during pregnancy; Prevalence of maternal chlamydia trachomatis, neisseria gonorrhoea, and vaginal trichomoniasis infection at 4 weeks after delivery
Expected Total Enrollment:  1320

Maternal anaemia, preterm deliveries and low birth weight are common in Sub-Saharan Africa and contribute significantly to the ill-health of pregnant women and infants. The present study is based on the assumption that these adverse outcomes can be prevented by improved antimicrobial management of malaria and sexually transmitted infections (STI) among pregnant women. To test the hypothesis, a randomised clinical trial following Good Clinical Practice (GCP) is being carried out in Malawi, South-Eastern Africa.

A total of 1320 consenting women who present at a rural antenatal clinic after 14 but before 26 completed gestation weeks will be enrolled. One third of the women will receive antenatal care according to national recommendations, including regular visits to health centre, screening for pregnancy complications, haematinic and vitamin A supplementation and two doses of presumptive malaria treatment with sulfadoxine-pyrimethamine. Another third will receive otherwise the same care, but sulfadoxine-pyrimethamine treatment is given at monthly intervals. The final third receives standard antenatal care, sulfadoxine-pyrimethamine treatment at monthly intervals and two doses of presumptive STI treatment with azithromycin. Women are monitored throughout pregnancy and delivery and the newborns will be followed up for one year.

The primary outcome measure is proportion of preterm births in the three study groups. Secondary maternal outcomes include anaemia and malaria parasitaemia during pregnancy, at delivery and at 1, 3, and 6 months after delivery, gestational weight gain and morbidity and STI prevalence after delivery. Secondary child outcomes consist of proportion of babies with low birth weight, mean birth weight, incidence of malnutrition during infancy, and mortality. Additionally, information is collected on the development of malaria-specific humoral immunity in pregnancy and participant experiences from the study. Participant safety is systematically monitored throughout the intervention.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Signed informed consent
• Age 15+ years
• Ultrasound confirmed pregnancy
• Quickening
• Foetal age 14-26 gestation weeks
• Maternal availability for follow-up during the entire study period

Exclusion Criteria:

• Known maternal tuberculosis, diabetes, kidney disease or liver disease
• Any severe acute illness warranting hospital referral at enrolment visit
• Mental disorder that may affect comprehension of the study or success of follow-up
• Twin pregnancy
• Pregnancy complications evident at enrolment visit (moderate to severe oedema, blood Hb concentration < 50 g / l, systolic blood pressure > 160 mmHg or diastolic BP > 100 mmHg)
• Prior receipt of azithromycin during this pregnancy
• Receipt of sulfadoxine and pyrimethamine within 28 days of enrollment
• Known allergy to drugs containing sulfonamides, macrolides or pyrimethamine
• History of anaphylaxis
• History of any serious allergic reaction to any substance, requiring emergency medical care
• Concurrent participation in any other clinical trial

Please refer to this study by ClinicalTrials.gov identifier  NCT00131235

Per Ashorn, MD, PhD      +358 40 7280 354    per.ashorn@iki.fi
Kenneth M Maleta, MBBS, PhD      +265 9 232 202    kmaleta@medcol.mw

Malawi, Mangochi District
      College of Medicine, University of Malawi, Mangochi,  Mangochi District,  Malawi; Recruiting

Study chairs or principal investigators

Per Ashorn, MD, PhD,  Study Director,  University of Tampere, Medical School   
Kenneth M Maleta, MBBS, PhD,  Principal Investigator,  University of Malawi College of Medicine   
Teija Kulmala, MD, PhD,  Principal Investigator,  University of Tampere, School of Public Health   

Study ID Numbers:  SA-179787-1
Last Updated:  August 16, 2005
Record first received:  August 16, 2005
ClinicalTrials.gov Identifier:  NCT00131235
Health Authority: Malawi: College of Medicine Research and Ethics Committee
ClinicalTrials.gov processed this record on 2005-08-23