Enhancing Nutrition and Antenatal Infection Treatment for Maternal and Child Health in Ethiopia

NCT04171388 | Withdrawn Phase 4 DMC

• 1 other identifier: 2018P002479
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The ENAT study will test the impact of packages of antenatal interventions to enhance maternal nutrition and manage pregnancy infections on the outcomes of infant birth size, gestational length, and infant growth in the first 6 months of life. Approximately 5,280 pregnant women will be enrolled into the study from 12 health centers in the Amhara region of Ethiopia. Routine antenatal care will be strengthened in all health centers, and six health centers will be randomized to additionally provide a nutritional intervention including daily multiple-micronutrient or a fortified balanced-energy protein supplement for malnourished women. Women across all 12 health centers will be individually randomized to receive one of three infection management interventions in pregnancy: 1) enhanced infection management package (screening-treatment for urinary tract infections and sexually transmitted infections, presumptive deworming); 2) presumptive azithromycin (2g at \<24 wks and a second dose at least 4 weeks later); or 3) placebo. The women and their infants will be followed until 6 months postpartum. Outcomes of interest include birth size (weight, length), gestational age, maternal weight gain in pregnancy, maternal anemia, antimicrobial resistance, and infant size at 6 months.

Conditions

Low Birthweight; Preterm Birth; Maternal; Malnutrition, Affecting Fetus; Sexually Transmitted Diseases; Urinary Tract Infections; Pregnancy and Infectious Disease

Keywords

Low birthweight; Preterm birth; Maternal nutrition; Small for gestational age; Chlamydia; Gonorrhea; Urinary tract infection; Presumptive antibiotics

Outcome Measures

Primary Outcomes (2)

• Birth weight

  Mean infant weight (g) among live born infants measured \<72 hour of delivery

  Within 72 hours of birth

• Birth length

  Mean infant length (cm) among live born infants measured \<72 hours of delivery

  Within 72 hours of birth

Secondary Outcomes (10)

• Gestational age

  Birth

• Preterm birth

  Birth

• Small-for-gestational age (SGA)

  within 72 hours of birth

• Low birthweight

  within 72 hours of birth

• Length-for-age

  Birth, 6 months

Study Arms (6)

Routine care: Placebo

PLACEBO COMPARATOR

In all pregnancies presenting at all centers, routine antenatal care will be strengthened: * Provision of iron-folic acid and tetanus toxoid vaccine * Screening for anemia and blood pressure * Screening/treatment of HIV, syphilis, malaria, tuberculosis Placebo tablets will be administered twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.

Drug: Placebo oral tablet 500 mg

Routine care: Azithromycin

EXPERIMENTAL

Azithromycin will be provided twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.

Drug: Azithromycin 500 mg

Routine care: Enhanced Infection Management Package (EIMP)

EXPERIMENTAL

At the study enrollment visit, pregnant women will receive presumptive deworming (albendazole) and screening for urinary tract infection and sexually transmitted infections (chlamydia and gonorrhea). Women with identified infections will be treated with appropriate antibiotics. A second dose of albendazole will be given at a follow up ANC visit at least 4 weeks after enrollment.

Other: Enhanced Infection Management Package (EIMP)

Enhanced Nutrition Package (ENP): Placebo

EXPERIMENTAL

Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. Placebo tablets will be administered twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.

Dietary Supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement; Drug: Placebo oral tablet 500 mg

ENP: Azithromycin

EXPERIMENTAL

Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. Azithromycin will be provided twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.

Drug: Azithromycin 500 mg; Dietary Supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement

ENP: EIMP

EXPERIMENTAL

Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. At the study enrollment visit, pregnant women will receive presumptive deworming (albendazole) and screening for urinary tract infection and sexually transmitted infections (chlamydia and gonorrohea). Women with identified infections will be treated with appropriate antibiotics. A second dose of albendazole will be given at a follow up ANC visit at least 4 weeks after enrollment.

Dietary Supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement; Other: Enhanced Infection Management Package (EIMP)

Interventions

Azithromycin 500 mg DRUG

Azithromycin 500mg (Kern Pharma): 2g (4 tablets) at 2 time points during pregnancy: enrollment (\<=24 weeks gestation), and follow-up ANC at least 4 weeks later

ENP: Azithromycin; Routine care: Azithromycin

Multiple Micronutrient or Fortified Balanced Energy Protein Supplement DIETARY_SUPPLEMENT

Daily multiple micronutrient (MMN) tablet (Contract Pharmacal Corp) for women with mid-upper arm circumference (MUAC) \>=23 cm, OR Daily fortified balanced energy protein (BEP) supplement (DSM South Africa; Faffa Food Products): Fortified corn-soy blend (784 kcal/day) for women with MUAC \<23 cm

ENP: Azithromycin; ENP: EIMP; Enhanced Nutrition Package (ENP): Placebo

Placebo oral tablet 500 mg DRUG

Placebo 500mg (Idifarma): 2g (4 tablets) at 2 time points during pregnancy; enrollment (\<24 weeks gestation), and follow up ANC at least 4 weeks later

Enhanced Nutrition Package (ENP): Placebo; Routine care: Placebo

Enhanced Infection Management Package (EIMP) OTHER

ENROLLMENT VISIT: Screening for bacteriuria with urine culture, and antimicrobial susceptibility testing; Screening for chlamydia and gonorrhea with Cepheid GeneXpert; Presumptive deworming with albendazole 500mg. FOLLOWUP TREATMENT VISIT: For women with identified urinary tract infection or asymptomatic bacteriuria, treatment with antibiotics based on antimicrobial susceptibility patterns. For women with identified chlamydia or gonorrhea, treatment of woman (and partner) with appropriate antibiotics. Test of cure sample and retreatment of infection. Second deworming with albendazole at least 4 weeks after enrollment ANC visit.

ENP: EIMP; Routine care: Enhanced Infection Management Package (EIMP)

Eligibility Criteria

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

You may qualify if:

• Pregnant women \<=24 weeks gestation with a viable pregnancy based on a best clinical algorithm (LMP and/or symphysis fundal height)

You may not qualify if:

• Pregnant women presenting at enrollment \>24 weeks
• Pregnant women presenting with non-viable fetus
• Women who do not intend to deliver in the study catchment area
• Known allergy to Azithromycin or macrolide antibiotic
• Women who refuse to provide consent

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Addis Continental Institute of Public Health: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator
• Boston Children's Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Harvard School of Public Health (HSPH): collaborator
• Amhara Public Health Institute: collaborator
• Jhpiego: collaborator

MeSH Terms

Conditions

Premature Birth; Malnutrition; Sexually Transmitted Diseases; Urinary Tract Infections; Communicable Diseases; Chlamydia Infections; Gonorrhea

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases; Infections; Genital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urologic Diseases; Female Urogenital Diseases; Male Urogenital Diseases; Chlamydiaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sexually Transmitted Diseases, Bacterial; Neisseriaceae Infections

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking of Azithro vs. Placebo arm only
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Hospitalist, Director of Global Newborn Health, Department of Pediatric Newborn Medicine

Model Details: 2x3 factorial randomized controlled trial, with cluster randomization of nutrition interventions and individually randomized infection management interventions

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: November 20, 2019
• Study Start: March 1, 2020
• Primary Completion: May 28, 2021
• Study Completion: November 30, 2021
• Last Updated: August 17, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share