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

NCT ID: NCT04171388

Last Updated: 2020-08-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-01
• Study Completion Date: 2021-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Routine care: Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet 500 mg

Intervention Type: 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

Routine care: Azithromycin

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

Group Type: EXPERIMENTAL

Azithromycin 500 mg

Intervention Type: 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

Routine care: Enhanced Infection Management Package (EIMP)

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.

Group Type: EXPERIMENTAL

Enhanced Infection Management Package (EIMP)

Intervention Type: 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.

Enhanced Nutrition Package (ENP): Placebo

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.

Group Type: EXPERIMENTAL

Multiple Micronutrient or Fortified Balanced Energy Protein Supplement

Intervention Type: 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

Placebo oral tablet 500 mg

Intervention Type: 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

ENP: Azithromycin

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.

Group Type: EXPERIMENTAL

Azithromycin 500 mg

Intervention Type: 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

Multiple Micronutrient or Fortified Balanced Energy Protein Supplement

Intervention Type: 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: EIMP

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.

Group Type: EXPERIMENTAL

Multiple Micronutrient or Fortified Balanced Energy Protein Supplement

Intervention Type: 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

Enhanced Infection Management Package (EIMP)

Intervention Type: 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.

Interventions

Azithromycin 500 mg

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

Intervention Type: DRUG

Multiple Micronutrient or Fortified Balanced Energy Protein 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

Intervention Type: DIETARY_SUPPLEMENT

Placebo oral tablet 500 mg

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

Intervention Type: DRUG

Enhanced Infection Management Package (EIMP)

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Addis Continental Institute of Public Health

OTHER

Sponsor Role: collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role: collaborator

Amhara Public Health Institute

UNKNOWN

Sponsor Role: collaborator

Jhpiego

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Anne Lee

Pediatric Hospitalist, Director of Global Newborn Health, Department of Pediatric Newborn Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

2018P002479

Identifier Type: -

Identifier Source: org_study_id