Gestational Sulfadoxine-pyrimethamine and Azithromycin Treatment to Prevent Preterm Birth

NCT ID: NCT00131235

Last Updated: 2025-03-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1320 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-12-31

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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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

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Malaria Sexually Transmitted Diseases Preterm Birth Pregnancy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Control

Standard antenatal care as described in intervention

Group Type PLACEBO_COMPARATOR

Sulfadoxine-pyrimethamine treatment twice during pregnancy

Intervention Type 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.

Monthly SP

Standard antenatal care + monthly intermittent presumptive treatment of malaria with sulfadoxine pyrimethamine, as described in intervention

Group Type EXPERIMENTAL

Sulfadoxine-pyrimethamine at 4-week intervals

Intervention Type 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.

AZI-SP

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

Group Type EXPERIMENTAL

Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice

Intervention Type 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.

Interventions

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Sulfadoxine-pyrimethamine treatment twice during pregnancy

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.

Intervention Type DRUG

Sulfadoxine-pyrimethamine at 4-week intervals

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.

Intervention Type DRUG

Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice

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.

Intervention Type DRUG

Other Intervention Names

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Control Monthly SP Azi-SP

Eligibility Criteria

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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
Minimum Eligible Age

15 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Academy of Finland

OTHER

Sponsor Role collaborator

Foundation for Paediatric Research, Finland

OTHER

Sponsor Role collaborator

Tampere University

OTHER

Sponsor Role lead

Responsible Party

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Per Ashorn

Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Per Ashorn, MD, PhD

Role: STUDY_DIRECTOR

Tampere University, Faculty of Medicine and Health Technology

Kenneth M Maleta, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

Kamuzu University of Health Sciences

Locations

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College of Medicine, University of Malawi

Mangochi, Mangochi District, Malawi

Site Status

Countries

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Malawi

References

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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.

Reference Type BACKGROUND
PMID: 23403684 (View on PubMed)

Hallamaa 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.

Reference Type BACKGROUND
PMID: 29472491 (View on PubMed)

Luntamo 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.

Reference Type RESULT
PMID: 21118924 (View on PubMed)

Rantala 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.

Reference Type RESULT
PMID: 20925928 (View on PubMed)

Aitken 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.

Reference Type RESULT
PMID: 22299027 (View on PubMed)

Aitken 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.

Reference Type RESULT
PMID: 20350189 (View on PubMed)

Luntamo 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.

Reference Type RESULT
PMID: 23432801 (View on PubMed)

Xu 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.

Reference Type RESULT
PMID: 24225354 (View on PubMed)

Lin 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.

Reference Type RESULT
PMID: 23198734 (View on PubMed)

Pons-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.

Reference Type DERIVED
PMID: 39324693 (View on PubMed)

Videman 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.

Reference Type DERIVED
PMID: 34479861 (View on PubMed)

Luntamo 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.

Reference Type DERIVED
PMID: 22829919 (View on PubMed)

Related Links

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http://www.medcol.mw/

College of Medicine home page

Other Identifiers

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SA-179787-1

Identifier Type: -

Identifier Source: org_study_id

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