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

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04171388

Collaborator

Addis Continental Institute of Public Health (Other), Johns Hopkins Bloomberg School of Public Health (Other), Boston Children's Hospital (Other), Beth Israel Deaconess Medical Center (Other), Harvard School of Public Health (HSPH) (Other), Amhara Public Health Institute (Other), Jhpiego (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Low Birthweight Preterm Birth Maternal; Malnutrition, Affecting Fetus Sexually Transmitted Diseases Urinary Tract Infections Pregnancy and Infectious Disease	Drug: Azithromycin 500 mg Dietary Supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement Drug: Placebo oral tablet 500 mg Other: Enhanced Infection Management Package (EIMP)	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

2x3 factorial randomized controlled trial, with cluster randomization of nutrition interventions and individually randomized infection management interventions2x3 factorial randomized controlled trial, with cluster randomization of nutrition interventions and individually randomized infection management interventions

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Masking of Azithro vs. Placebo arm only

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2020

Anticipated Primary Completion Date :

May 28, 2021

Anticipated Study Completion Date :

Nov 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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.	Drug: 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
Experimental: 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.	Drug: 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
Experimental: 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.	Other: 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.
Experimental: 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.	Dietary Supplement: 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 Drug: 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
Experimental: 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.	Drug: 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 Dietary Supplement: 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
Experimental: 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.	Dietary Supplement: 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 Other: 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.

Outcome Measures

Primary Outcome Measures

Birth weight [Within 72 hours of birth]
Mean infant weight (g) among live born infants measured <72 hour of delivery
Birth length [Within 72 hours of birth]
Mean infant length (cm) among live born infants measured <72 hours of delivery

Secondary Outcome Measures

Gestational age [Birth]
Mean gestational age at delivery
Preterm birth [Birth]
Proportion of pregnancies resulting in spontaneous birth <37 weeks gestation among all births
Small-for-gestational age (SGA) [within 72 hours of birth]
Proportions of newborns born SGA (<10% birthweight for gestational age and sex) among live born infants whose birthweight if measured within 72 hours of delivery.
Low birthweight [within 72 hours of birth]
Proportion of newborns born with weight <2500 g among liveborn infants whose weight is measured within 72 hours of delivery
Length-for-age [Birth, 6 months]
Mean Length-for-age Z scores at birth and 6 months of age among live born infants based on the WHO growth reference standards (WHO 2006)
Weight-for-age [Birth, 6 months]
Mean Weight-for-age Z scores at birth and 6 months of age among live born infants based on the WHO growth reference standards (WHO 2006)
Rate of weight gain in pregnancy [From date of first 2nd trimester antenatal care (ANC) visit until date of last ANC visit before birth, assessed up to 6 months]
Maternal weight gain (kg) per week gestation in the 2nd and 3rd trimester
Maternal anemia [Third trimester antenatal care visit (28-40 weeks gestation)]
Mean hemoglobin concentration
Stillbirth [Birth]
Rate of stillbirths per 1000 births
Prevalence of nasopharyngeal macrolide resistance in mothers-infants [1 and 6 months post-partum]
Prevalence of nasopharyngeal macrolide resistance among S. pneumoniae isolates in mothers-infants at 1 and 6 months postpartum

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Anne Lee, Pediatric Hospitalist, Director of Global Newborn Health, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital

ClinicalTrials.gov Identifier:

NCT04171388

Other Study ID Numbers:

2018P002479

First Posted:

Nov 20, 2019

Last Update Posted:

Aug 17, 2020

Last Verified:

Aug 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Anne Lee, Pediatric Hospitalist, Director of Global Newborn Health, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital

Low birthweight

Preterm birth

Maternal nutrition

Small for gestational age

Chlamydia

Gonorrhea

Urinary tract infection

Presumptive antibiotics

Additional relevant MeSH terms:

Infections

Communicable Diseases

Urinary Tract Infections