Gestational Sulfadoxine-pyrimethamine and Azithromycin Treatment to Prevent Preterm Birth

This study has been completed.
Sponsor:
Collaborators:
Academy of Finland
Foundation for Paediatric Research, Finland
Information provided by (Responsible Party):
Per Ashorn, University of Tampere
ClinicalTrials.gov Identifier:
NCT00131235
First received: August 16, 2005
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Malaria
Sexually Transmitted Diseases
Preterm Birth
Pregnancy
Drug: Sulfadoxine-pyrimethamine treatment twice during pregnancy
Drug: Sulfadoxine-pyrimethamine at 4-week intervals
Drug: Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by University of Tampere:

Primary Outcome Measures:
  • Proportion of preterm births [ Time Frame: once, after delivery ] [ Designated as safety issue: No ]
  • Number of serious and any adverse events [ Time Frame: Cumulative during pregnancy and neonatal period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of low birth weight babies [ Time Frame: Once, after delivery ] [ Designated as safety issue: No ]
  • Mean birth weight [ Time Frame: Once, after delivery ] [ Designated as safety issue: No ]
  • Mean duration of gestation [ Time Frame: Once, after delivery ] [ Designated as safety issue: No ]
  • Percentage of low chest circumference at birth [ Time Frame: Once, after delivery ] [ Designated as safety issue: No ]
  • Percentage of low chest or head circumference at birth [ Time Frame: Once, after delivery ] [ Designated as safety issue: No ]
  • Incidence of moderate underweight during infancy [ Time Frame: Cumulative during infancy ] [ Designated as safety issue: No ]
  • Perinatal, neonatal and infant mortality [ Time Frame: Cumulative during infancy ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percentage of women with peripheral blood malaria parasitaemia and mean parasite density at enrolment, at 32 gestational weeks and at delivery [ Time Frame: at enrolment, at 32 weeks, and at delivery ] [ Designated as safety issue: No ]
  • Percentage of women with cord blood and placental malaria parasitaemia at delivery [ Time Frame: At delivery ] [ Designated as safety issue: No ]
  • Maternal weight gain during pregnancy [ Time Frame: Once after pregancy ] [ Designated as safety issue: No ]
  • Mean number of maternal illness days during pregnancy [ Time Frame: Cumulative during pregnancy ] [ Designated as safety issue: No ]
  • Prevalence of maternal chlamydia trachomatis, neisseria gonorrhoea, and vaginal trichomoniasis infection at 4 weeks after delivery [ Time Frame: At 4 weeks after delivery ] [ Designated as safety issue: No ]

Enrollment: 1320
Study Start Date: December 2003
Study Completion Date: March 2012
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
Standard antenatal care as described in intervention
Drug: 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.

Experimental: Monthly SP
Standard antenatal care + monthly intermittent presumptive treatment of malaria with sulfadoxine pyrimethamine, as described in intervention
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.

Experimental: 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
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.


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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131235

Locations
Malawi
College of Medicine, University of Malawi
Mangochi, Mangochi District, Malawi
Sponsors and Collaborators
University of Tampere
Academy of Finland
Foundation for Paediatric Research, Finland
Investigators
Study Director: Per Ashorn, MD, PhD University of Tampere, Medical School
Principal Investigator: Kenneth M Maleta, MBBS, PhD University of Malawi College of Medicine
Principal Investigator: Teija Kulmala, MD, PhD University of Tampere, School of Public Health
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Per Ashorn, Professor of International Health, University of Tampere
ClinicalTrials.gov Identifier: NCT00131235     History of Changes
Other Study ID Numbers: SA-179787-1
Study First Received: August 16, 2005
Last Updated: January 21, 2014
Health Authority: Malawi: College of Medicine Research and Ethics Committee

Keywords provided by University of Tampere:
Malaria
STI
Pregnancy
Prevention
Preterm birth
Low birth weight
Sub-Saharan Africa

Additional relevant MeSH terms:
Malaria
Premature Birth
Sexually Transmitted Diseases
Protozoan Infections
Parasitic Diseases
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Infection
Virus Diseases
Genital Diseases, Male
Genital Diseases, Female
Fanasil, pyrimethamine drug combination
Sulfadoxine
Pyrimethamine
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014