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NCT Number: NCT00131235

Gestational Sulfadoxine-pyrimethamine and Azithromycin Treatment to Prevent Preterm Birth

The purpose of this study is to examine whether 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 for the mother and the foetus/newborn.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Malaria Communicable Diseases Disease Attributes Female Urogenital Diseases and Pregnancy Complications Genital Diseases Infections Mosquito-Borne Diseases Obstetric Labor Complications Obstetric Labor, Premature Parasitic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Pregnancy Pregnancy Complications Premature Birth Preterm Birth Protozoan Infections Sexually Transmitted Diseases Urogenital Diseases Vector Borne Diseases

Age range

15 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

College of Medicine, University of Malawi

Mangochi, Mangochi District, Malawi

About this study

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 newborn growth will be followed up for five years.

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, growth in infancy and childhood, incidence of malnutrition in infancy and childhood, 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.

There have been two edits two the trial protocol, since the original approval. In the first one, there was an amendment to follow child growth and mortality until and child development at 5 years of age, with visits at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months. In the second amendment, there was an addition to monitor child antropometrics, physical, mental, and social health at and mortality by 10-12 years of age.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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 enrollment visit
  • Mental disorder that may affect comprehension of the study or success of follow-up
  • Twin pregnancy
  • Pregnancy complications evident at enrollment visit (moderate to severe oedema, blood hemoglobin [Hb] concentration < 50 g/l, systolic blood pressure [BP] > 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

Treatment and study plan

Sulfadoxine-pyrimethamine treatment twice during pregnancy

Drug

Sulfadoxine-pyrimethamine, 3 tablets (each containing 500mg of sulfadoxine and 25mg of pyrimethamine), taken once at antenatal care enrolment (14.0-25.9 gestation weeks) and another time between 28.0 and 33.9 gestation weeks.

2 placebo tablets for azithromycin taken at the same time points.

Other names: Control

Sulfadoxine-pyrimethamine at 4-week intervals

Drug

Sulfadoxine-pyrimethamine, 3 tablets (each containing 500mg of sulfadoxine and 25mg of pyrimethamine), taken once at antenatal care enrolment (14.0-25.9 gestation weeks) and then at 4 week intervals until 37.0 gestation weeks.

2 placebo tablets for azithromycin taken once at antenatal care enrolment (14.0-25.9 gestation weeks) and another time between 28.0 and 33.9 gestation weeks.

Other names: Monthly SP

Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice

Drug

Sulfadoxine-pyrimethamine, 3 tablets (each containing 500mg of sulfadoxine and 25mg of pyrimethamine), taken once at antenatal care enrolment (14.0-25.9 gestation weeks) and then at 4 week intervals until 37.0 gestation weeks.

2 azithromycin tablets (each 500 mg) taken once at antenatal care enrolment (14.0-25.9 gestation weeks) and another time between 28.0 and 33.9 gestation weeks.

Other names: Azi-SP

Primary outcomes

  1. Proportion of preterm births

    Time frame: once, after delivery

    Proportion of babies who are born before 37 completed gestation weeks

  2. Number of serious adverse events

    Time frame: Cumulative during pregnancy and neonatal period

    Death, life-threatening event, hospitalization, congenital anomaly, or any othe condition consedered an SAE by a study physician

Secondary outcomes

  1. Percentage of low birth weight babies

    Time frame: Once, after delivery

    Birth weight < 2500 g

  2. Mean birth weight

    Time frame: Once, after delivery

    Measured in grams

  3. Mean duration of gestation

    Time frame: Once, after delivery

    Measured in gestation weeks, expressed to one deciman,

  4. Percentage of low head circumference at birth

    Time frame: Once, after delivery

    Below 2 standard deviations of the mean of international reference population

  5. Incidence of moderate underweight during infancy or childhood

    Time frame: Cumulative during infancy and childhood

    weight for age Z-score < -2

  6. Perinatal mortality

    Time frame: Cumulative until 7 days of post-natal life

    Stillbirths after 22 gestation weeks or within first 7 days of life / 1000 live births

  7. Neonatal mortality

    Time frame: Cumulative until 28 days of post-natal life

    Deaths within first 28 days of life / 1000 live births

  8. Infant mortality

    Time frame: Cumulative until 365 days of post-natal life

    Deaths within first 265 days of life / 1000 live births

  9. Mean maternal blood haemoglobin concentration at each antenatal visit and at 1, 3, and 6 months after delivery

    Time frame: Several antenatal and postnatal visits

    Measured with hemocue meter, expressed as grams / liter

  10. Percentage of women with mild, moderate or severe anaemia at every antenatal visit and at 1, 3, and 6 months after delivery

    Time frame: Several antenatal and postnatal visits

    Cut-offs for mild, moderate and severa anaemia 110 g / l - 80 g / l - 50 g / l

  11. Percentage of women with peripheral blood malaria parasitaemia at 32 gestational weeks and at delivery

    Time frame: At enrolment, every 4 weeks thereafter and at delivery

    Measured with microscopy from fresh blood slides and with real-time PCR from dried blood spots

  12. Maternal weight gain during pregnancy

    Time frame: Cumulative during pregnancy

    grams / gestation week

  13. Mean number of maternal illness days during pregnancy

    Time frame: Cumulative during pregnancy

    Self reported illness symptoms

  14. Prevalence of maternal chlamydia trachomatis, neisseria gonorrhoea, and vaginal trichomoniasis infection at 4 weeks after delivery

    Time frame: At 4 weeks after delivery

    Chlamydia and gonorhoea measured from urine samples with a PCR, vaginal trichomoniasis measures with a wet microscopy

  15. Attained lenght / height

    Time frame: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age

    Measured as length until 2 years of age, then height; expressed in cm (one decimal) and as length / heigh for age Z-score

  16. Attained weight

    Time frame: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age

    Expressed in kg with two decimals and as weight for age Z-score

  17. Nutritional status

    Time frame: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age

    Mid-upper arm circumference, in mm (no decimals)

  18. Attained head circumference

    Time frame: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age

    Head circumference, in mm, no decimals

  19. Childhood mortality, % of subjects who have died by the 10-12 year follow-up visit

    Time frame: Cumulative incidence by 10-12 years of age

    Deaths, information obtained from parents or other adults who have lived in the same household with the child

  20. Motor development, Griffiths test, sub-score

    Time frame: 5 years of age

    Summary score from questions in the gross motor and fine motor domain questions

  21. Social development, Griffiths test, sub-score

    Time frame: 5 years of age

    Summary score from questions in the social development domain questions

  22. Cognitive development, Raven's colour matrix, score

    Time frame: 10-12 years of age

    Summary score from 36 questions in the Raven's colour matrix test

  23. Reaction time, milliseconds

    Time frame: 10-12 years of age

    This will be tested with an eye-tracking device (Tobii). Participants are asked to look from the fixation point to different directions or fixate the gaze at one point. We will measure the horizontal eye-movements (saccades) and calculate the reaction times, scoring the task correct/incorrect (direction).

    This eye-tracking system is based on a Pupil Centre Corneal Reflection (PCCR) technique, in which near infrared illumination is reflected on the cornea relative to the center of the pupil. The eye-tracking cameras capture the light reflections and create a 3D model of the eye and head-position to track the participant's point of gaze at high temporal and spatial accuracy (60 Hz/0.4°). The results will be stored automatically into a data base.

  24. Systolic blood pressure, mmHg

    Time frame: 10-12 years of age

    Will use oscillometric Mobil o Graph blood pressure monitoring system (accuracy +/- 3 mmHg), when the child is first sitting, then standing and last lying down.

  25. Diastolic blood pressure, mmHg

    Time frame: 10-12 years of age

    Will use oscillometric Mobil o Graph blood pressure monitoring system (accuracy +/- 3 mmHg), when the child is first sitting, then standing and last lying down.

  26. Central blood pressure, mmHg

    Time frame: 10-12 years of age

    Will use oscillometric Mobil o Graph blood pressure monitoring system (accuracy +/- 3 mmHg), when the child is first sitting, then standing and last lying down.

  27. Pulse rate, beats / minutes

    Time frame: 10-12 years of age

    Will use oscillometric Mobil o Graph blood pressure monitoring system. We will measure pulse rate / minutes, when the child is first sitting, then standing and last lying down.

  28. Vascular resistance, mmHg·min/l

    Time frame: 10-12 years of age

    Will use oscillometric Mobil o Graph blood pressure monitoring system. We will measure vascular resistance, when the child is first sitting, then standing and last lying down.

  29. Lean body mass, expressed in kg, with one decimal

    Time frame: 10-12 years of age

    Body composition measured with 8-polar biompedance method (Seca® mBCA 515 Medical Body Composition Analyser), validated with Deuterium Dilution Technique with Analysis of Saliva Samples by Fourier Transform Infrared Spectrometry (FTIR)

  30. Fat mass, expressed in kg, with one decimal

    Time frame: 10-12 years of age

    Body composition measured with 8-polar biompedance method (Seca® mBCA 515 Medical Body Composition Analyser), validated with Deuterium Dilution Technique with Analysis of Saliva Samples by Fourier Transform Infrared Spectrometry (FTIR)

  31. Fat percentage, expressed proportion of body weight (per cent, with one decimal)

    Time frame: 10-12 years of age

    Body composition measured with 8-polar biompedance method (Seca® mBCA 515 Medical Body Composition Analyser), validated with Deuterium Dilution Technique with Analysis of Saliva Samples by Fourier Transform Infrared Spectrometry (FTIR)

  32. Self-rated well-being, score

    Time frame: 10-12 years of age

    Self-reported well-being will be measured with 11 question panel with rating from 1-5 expressed as smileys. The questions consider about "how happy you are about the things you own, school, house you live, food, clothes, other pupils, friends, the family, safety feeling, the way you look, with yourself". Score for self-reported well-being will be calculated as a sum of ratings for each item divided by the number of items with non-missing data. There are two items related to the child's school and they are not applicable if the child does not go to school. The minimum score for self-reported well-being is 1 and the maximum is 5, and the score will be expressed with one decimal.

Sponsors and collaborators

Lead sponsor

Tampere University

Other

Collaborators

  • Academy of Finland
  • Foundation for Paediatric Research, Finland

Registry information

Official study title

Lungwena Antenatal Intervention Study. A Single-centre Intervention Trial in Rural Malawi, Testing Maternal and Infant Health Effects of Presumptive Intermittent Treatment of Pregnant Women With Sulfadoxine-pyrimethamine and Azithromycin

Important dates

Study start
2003
Primary completion
2007
Study completion
2027
First posted
Aug 17, 2005
Registry last updated
Mar 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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