MalariaPhase 3NCT00131235
Gestational Sulfadoxine-pyrimethamine and Azithromycin Treatment to Prevent Preterm Birth
A Phase 3 study testing Sulfadoxine-pyrimethamine treatment twice during pregnancy, Sulfadoxine-pyrimethamine at 4-week intervals and Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice in people with Malaria and Sexually Transmitted Diseases, run by Tampere University at 1 site in Malawi.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 15 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Malaria, Sexually Transmitted Diseases, Preterm Birth
- What is being tested?
- Sulfadoxine-pyrimethamine treatment twice during pregnancy, Sulfadoxine-pyrimethamine at 4-week intervals and Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,320 participants
- Where
- 1 siteMalawi
- Study dates
- Dec 2003to 31 Dec 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Malawi1 site
College of Medicine, University of Malawi
Mangochi, Mangochi District
About this study
Official 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
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.
Read the detailed description
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.
- Conditions
- Malaria, Sexually Transmitted Diseases, Preterm Birth, Pregnancy
- Being tested
- Sulfadoxine-pyrimethamine treatment twice during pregnancy, Sulfadoxine-pyrimethamine at 4-week intervals, Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice
- Keywords
- Malaria, STI, Pregnancy, Prevention, Preterm birth, Low birth weight, Sub-Saharan Africa
- Medical subject headings
- Malaria, Sexually Transmitted Diseases, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sulfadoxine-pyrimethamine treatment twice during pregnancyDrug
Also called Control
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.
Sulfadoxine-pyrimethamine at 4-week intervalsDrug
Also called Monthly SP
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.
Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twiceDrug
Also called Azi-SP
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Standard antenatal care as described in intervention Receives: Drug: Sulfadoxine-pyrimethamine treatment twice during pregnancy |
| Monthly SP | Experimental | Standard antenatal care + monthly intermittent presumptive treatment of malaria with sulfadoxine pyrimethamine, as described in intervention Receives: Drug: Sulfadoxine-pyrimethamine at 4-week intervals |
| AZI-SP | Experimental | Standard antenatal care + monthly intermittent presumptive treatment of malaria with sulfadoxine pyrimethamine + two presumptive treatments of sexually transmitted infections and malaria with azithromycin, as described in intervention Receives: Drug: Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of preterm births
Proportion of babies who are born before 37 completed gestation weeks
Measured: once, after delivery
Number of serious adverse events
Death, life-threatening event, hospitalization, congenital anomaly, or any othe condition consedered an SAE by a study physician
Measured: Cumulative during pregnancy and neonatal period
Secondary outcomes (32)
Percentage of low birth weight babies
Birth weight < 2500 g
Measured: Once, after delivery
Mean birth weight
Measured in grams
Measured: Once, after delivery
Mean duration of gestation
Measured in gestation weeks, expressed to one deciman,
Measured: Once, after delivery
Percentage of low head circumference at birth
Below 2 standard deviations of the mean of international reference population
Measured: Once, after delivery
Incidence of moderate underweight during infancy or childhood
weight for age Z-score < -2
Measured: Cumulative during infancy and childhood
Perinatal mortality
Stillbirths after 22 gestation weeks or within first 7 days of life / 1000 live births
Measured: Cumulative until 7 days of post-natal life
Neonatal mortality
Deaths within first 28 days of life / 1000 live births
Measured: Cumulative until 28 days of post-natal life
Infant mortality
Deaths within first 265 days of life / 1000 live births
Measured: Cumulative until 365 days of post-natal life
Mean maternal blood haemoglobin concentration at each antenatal visit and at 1, 3, and 6 months after delivery
Measured with hemocue meter, expressed as grams / liter
Measured: Several antenatal and postnatal visits
Percentage of women with mild, moderate or severe anaemia at every antenatal visit and at 1, 3, and 6 months after delivery
Cut-offs for mild, moderate and severa anaemia 110 g / l - 80 g / l - 50 g / l
Measured: Several antenatal and postnatal visits
Percentage of women with peripheral blood malaria parasitaemia at 32 gestational weeks and at delivery
Measured with microscopy from fresh blood slides and with real-time PCR from dried blood spots
Measured: At enrolment, every 4 weeks thereafter and at delivery
Maternal weight gain during pregnancy
grams / gestation week
Measured: Cumulative during pregnancy
Mean number of maternal illness days during pregnancy
Self reported illness symptoms
Measured: Cumulative during pregnancy
Prevalence of maternal chlamydia trachomatis, neisseria gonorrhoea, and vaginal trichomoniasis infection at 4 weeks after delivery
Chlamydia and gonorhoea measured from urine samples with a PCR, vaginal trichomoniasis measures with a wet microscopy
Measured: At 4 weeks after delivery
Attained lenght / height
Measured as length until 2 years of age, then height; expressed in cm (one decimal) and as length / heigh for age Z-score
Measured: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age
Attained weight
Expressed in kg with two decimals and as weight for age Z-score
Measured: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age
Nutritional status
Mid-upper arm circumference, in mm (no decimals)
Measured: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age
Attained head circumference
Head circumference, in mm, no decimals
Measured: 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age
Childhood mortality, % of subjects who have died by the 10-12 year follow-up visit
Deaths, information obtained from parents or other adults who have lived in the same household with the child
Measured: Cumulative incidence by 10-12 years of age
Motor development, Griffiths test, sub-score
Summary score from questions in the gross motor and fine motor domain questions
Measured: 5 years of age
Social development, Griffiths test, sub-score
Summary score from questions in the social development domain questions
Measured: 5 years of age
Cognitive development, Raven's colour matrix, score
Summary score from 36 questions in the Raven's colour matrix test
Measured: 10-12 years of age
Reaction time, milliseconds
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.
Measured: 10-12 years of age
Systolic blood pressure, mmHg
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.
Measured: 10-12 years of age
Diastolic blood pressure, mmHg
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.
Measured: 10-12 years of age
Central blood pressure, mmHg
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.
Measured: 10-12 years of age
Pulse rate, beats / minutes
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.
Measured: 10-12 years of age
Vascular resistance, mmHg·min/l
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.
Measured: 10-12 years of age
Lean body mass, expressed in kg, with one decimal
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)
Measured: 10-12 years of age
Fat mass, expressed in kg, with one decimal
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)
Measured: 10-12 years of age
Fat percentage, expressed proportion of body weight (per cent, with one decimal)
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)
Measured: 10-12 years of age
Self-rated well-being, score
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.
Measured: 10-12 years of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2005 (estimated)
- Study startDec 2003
- Primary completionJun 2007
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tampere University
- Sponsor type
- University, hospital or other
- Collaborators
- Academy of Finland, Foundation for Paediatric Research, Finland
- Responsible party
- Principal investigator, Per Ashorn, Tampere University
- Investigators
- Per Ashorn, MD, PhD, Study director, Tampere University, Faculty of Medicine and Health TechnologyKenneth M Maleta, MBBS, PhD, Principal investigator, Kamuzu University of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00131235
- Sponsor's protocol ID
- SA-179787-1
- Status last verified
- Mar 2025
- First submitted
- 16 Aug 2005
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kayentao K, Garner P, van Eijk AM, Naidoo I, Roper C, Mulokozi A, MacArthur JR, Luntamo M, Ashorn P, Doumbo OK, ter Kuile FO. Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis. JAMA. 2013 Feb 13;309(6):594-604. doi: 10.1001/jama.2012.216231.
PubMed 23403684Hallamaa L, Cheung YB, Maleta K, Luntamo M, Ashorn U, Gladstone M, Kulmala T, Mangani C, Ashorn P. Child Health Outcomes After Presumptive Infection Treatment in Pregnant Women: A Randomized Trial. Pediatrics. 2018 Mar;141(3):e20172459. doi: 10.1542/peds.2017-2459.
PubMed 29472491Luntamo M, Kulmala T, Mbewe B, Cheung YB, Maleta K, Ashorn P. Effect of repeated treatment of pregnant women with sulfadoxine-pyrimethamine and azithromycin on preterm delivery in Malawi: a randomized controlled trial. Am J Trop Med Hyg. 2010 Dec;83(6):1212-20. doi: 10.4269/ajtmh.2010.10-0264.
PubMed 21118924Rantala AM, Taylor SM, Trottman PA, Luntamo M, Mbewe B, Maleta K, Kulmala T, Ashorn P, Meshnick SR. Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malar J. 2010 Oct 6;9:269. doi: 10.1186/1475-2875-9-269.
PubMed 20925928Aitken EH, Mbewe B, Luntamo M, Kulmala T, Beeson JG, Ashorn P, Rogerson SJ. Antibody to P. falciparum in pregnancy varies with intermittent preventive treatment regime and bed net use. PLoS One. 2012;7(1):e29874. doi: 10.1371/journal.pone.0029874. Epub 2012 Jan 27.
PubMed 22299027Aitken EH, Mbewe B, Luntamo M, Maleta K, Kulmala T, Friso MJ, Fowkes FJ, Beeson JG, Ashorn P, Rogerson SJ. Antibodies to chondroitin sulfate A-binding infected erythrocytes: dynamics and protection during pregnancy in women receiving intermittent preventive treatment. J Infect Dis. 2010 May 1;201(9):1316-25. doi: 10.1086/651578.
PubMed 20350189Luntamo M, Kulmala T, Cheung YB, Maleta K, Ashorn P. The effect of antenatal monthly sulphadoxine-pyrimethamine, alone or with azithromycin, on foetal and neonatal growth faltering in Malawi: a randomised controlled trial. Trop Med Int Health. 2013 Apr;18(4):386-97. doi: 10.1111/tmi.12074. Epub 2013 Feb 22.
PubMed 23432801Xu J, Luntamo M, Kulmala T, Ashorn P, Cheung YB. A longitudinal study of weight gain in pregnancy in Malawi: unconditional and conditional standards. Am J Clin Nutr. 2014 Feb;99(2):296-301. doi: 10.3945/ajcn.113.074120. Epub 2013 Nov 13.
PubMed 24225354Lin JT, Mbewe B, Taylor SM, Luntamo M, Meshnick SR, Ashorn P. Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria. Trop Med Int Health. 2013 Feb;18(2):175-8. doi: 10.1111/tmi.12028. Epub 2012 Nov 30.
PubMed 23198734Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.
PubMed 39324693Videman K, Hallamaa L, Heimonen O, Mangani C, Luntamo M, Maleta K, Ashorn P, Ashorn U. Child growth and neurodevelopment after maternal antenatal antibiotic treatment. Arch Dis Child. 2022 Apr;107(4):323-328. doi: 10.1136/archdischild-2021-322043. Epub 2021 Sep 3.
PubMed 34479861Luntamo M, Rantala AM, Meshnick SR, Cheung YB, Kulmala T, Maleta K, Ashorn P. The effect of monthly sulfadoxine-pyrimethamine, alone or with azithromycin, on PCR-diagnosed malaria at delivery: a randomized controlled trial. PLoS One. 2012;7(7):e41123. doi: 10.1371/journal.pone.0041123. Epub 2012 Jul 19.
PubMed 22829919