Gestational Sulfadoxine-pyrimethamine and Azithromycin Treatment to Prevent Preterm Birth

NCT00131235 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: SA-179787-1
• Study Type: interventional
• Target: 1,320
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria; Sexually Transmitted Diseases; Preterm Birth; Pregnancy

Keywords

Malaria; STI; Pregnancy; Prevention; Preterm birth; Low birth weight; Sub-Saharan Africa

Outcome Measures

Primary Outcomes (2)

• Proportion of preterm births

  Proportion of babies who are born before 37 completed gestation weeks

  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

  Cumulative during pregnancy and neonatal period

Secondary Outcomes (32)

• Percentage of low birth weight babies

  Once, after delivery

• Mean birth weight

  Once, after delivery

• Mean duration of gestation

  Once, after delivery

• Percentage of low head circumference at birth

  Once, after delivery

• Incidence of moderate underweight during infancy or childhood

  Cumulative during infancy and childhood

Study Arms (3)

Control

PLACEBO COMPARATOR

Standard antenatal care as described in intervention

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

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

Drug: Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice

Interventions

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.

Also known as: Control

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.

Also known as: Monthly SP

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.

Also known as: Azi-SP

AZI-SP

Eligibility Criteria

• Age: 15 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tampere University: lead
• Academy of Finland: collaborator
• Foundation for Paediatric Research, Finland: collaborator

Study Sites (1)

College of Medicine, University of Malawi

Mangochi, Mangochi District, Malawi

Location

Related Publications (12)

• 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.

  PMID: 23403684 BACKGROUND

• 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.

  PMID: 29472491 BACKGROUND

• 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.

  PMID: 21118924 RESULT

• 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.

  PMID: 20925928 RESULT

• 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.

  PMID: 22299027 RESULT

• 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.

  PMID: 20350189 RESULT

• 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.

  PMID: 23432801 RESULT

• 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.

  PMID: 24225354 RESULT

• 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.

  PMID: 23198734 RESULT

• 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.

  PMID: 39324693 DERIVED

• 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.

  PMID: 34479861 DERIVED

• 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.

  PMID: 22829919 DERIVED

Related Links

• College of Medicine home page

MeSH Terms

Conditions

Malaria; Sexually Transmitted Diseases; Premature Birth

Condition Hierarchy (Ancestors)

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

Study Officials

• Per Ashorn, MD, PhD

  Tampere University, Faculty of Medicine and Health Technology

  STUDY DIRECTOR

• Kenneth M Maleta, MBBS, PhD

  Kamuzu University of Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: August 16, 2005
• First Posted: August 17, 2005
• Study Start: December 1, 2003
• Primary Completion: June 1, 2007
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

MA (1)