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Trial of the Use of Antenatal Corticosteroids in Developing Countries

Trial of the Use of Antenatal Corticosteroids in Developing Countries

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01084096
Acronym
ACT
Enrollment
103117
Registered
2010-03-10
Start date
2011-10-31
Completion date
2014-04-30
Last updated
2024-12-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Preterm Birth

Keywords

Antenatal Corticosteroids, Preterm Birth, Diffusion

Brief summary

Multi-country two-arm, parallel cluster randomized controlled trial to reduce neonatal mortality through increasing the rate of antenatal corticosteroid administration to eligible women.

Detailed description

One of the United Nations Millennium Summit goals is to reduce the deaths of children \<5 years by two-thirds for 2015 (UN, 2000). Given that 38% of all under-five deaths worldwide occur in the first four weeks of life, the goal seems unattainable unless a significant fraction of the neonatal deaths are prevented (Darmstadt et al., 2005). Thus, the provision of health care during the perinatal period in developing countries is a top priority. Preterm birth is a major cause of neonatal mortality, currently responsible for 28% of the deaths overall. As the contribution of preterm birth to neonatal deaths is well above 50% (MacDorman et al., 2005) in middle and high income countries, it is expected that as low income countries improve their development, the relative importance of this cause will increase. One of the most powerful perinatal interventions to reduce neonatal mortality is the administration of antenatal corticosteroids to pregnant women at high risk of preterm birth. The primary objective will be to evaluate whether a cluster-level multifaceted intervention, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, reduces neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six African, Asian, and Latin American countries.

Interventions

BEHAVIORALIncreasing use of Antenatal Corticosteroids (ACS)

Intervention clusters: * Increasing administration of ACS to pregnant women at high risk of preterm birth (HRPB) by providing health providers with kits containing dexamethasone, syringes, and instructions. Eligible women receive four injections of 6 mg dexamethasone from the kit or regimen of choice at the site. * Improving identification of women at HRPB by diffusing recommendations for ACS use to health care providers, training health care providers to identify signs of preterm labor and eligibility criteria for ACS use, providing reminders to healthcare providers on the use of the kits, and using a color-coded tape to measure uterine height to estimate gestational age in women at HRPB with unknown gestational age. Control clusters: no specific intervention for comparison. Both intervention and control clusters: Birth attendants trained in essential newborn care of LBW infants and instructed to teach mothers how to provide care to premature infants.

Sponsors

RTI International
CollaboratorOTHER
Tulane University School of Medicine
CollaboratorOTHER
Institute for Clinical Effectiveness and Health Policy
CollaboratorOTHER
University of Alabama at Birmingham
CollaboratorOTHER
University Teaching Hospital, Lusaka, Zambia
CollaboratorOTHER
University of Colorado, Denver
CollaboratorOTHER
Universidad Francisco Marroquín
CollaboratorOTHER
Jawaharlal Nehru Medical College
CollaboratorOTHER
Christiana Care Health Services
CollaboratorOTHER
Aga Khan University
CollaboratorOTHER
Columbia University
CollaboratorOTHER
Indiana University
CollaboratorOTHER
Moi Univeristy
CollaboratorOTHER
Lata Medical Research Foundation, Nagpur
CollaboratorOTHER
Massachusetts General Hospital
CollaboratorOTHER
NICHD Global Network for Women's and Children's Health
Lead SponsorNETWORK

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Healthy volunteers
Yes

Inclusion criteria

This is an intent-to-treat design and thus all pregnancy outcomes of women who deliver in the study clusters and provide consent will be collected. Cluster-level inclusion criteria include * At least 250 deliveries per year. * Birth attendants within the health cluster will be consented to participate Participant-level inclusion criteria include all pregnant women living in and delivering in the study cluster who: * Are between 24 and 36 weeks GA; * Present with signs of preterm labor, amniotic fluid leakage, hemorrhage, or hypertension; * Provide consent for injection or present to a facility where it is standard of care.

Exclusion criteria

* There will not be any specific

Design outcomes

Primary

MeasureTime frameDescription
Neonatal Mortality Rate at 28 Days in <5th Percentile Birth Weight Infants (as a Proxy Measure for Prematurity)Birth to 28 daysNeonatal deaths before 28 days per 1,000 live births among \<5th %tile birth weight infants. The \<5th %tile birth weight group was a proxy for preterm. Site-specific cutoffs from pretrial data were 2,450g-Argentina, 2,400g-Zambia, 2,267g-Guatemala, 2,000g-Belgaum, India, 2,150g-Pakistan, 2,000g-Nagpur, India, and 2,500g-Kenya. Infants were classified as \<5th %tile on the basis of measured birth weights. Estimated weights by clinical assessment were used when measured weights were unavailable; those missing weights were classified as \<5th %tile (since based on historical data, most of the missing data were for preterm infants). We used birth weight rather than gestational age (GA) for the primary analysis subgroup because many women in the registry had missing or uncertain GA, ultrasound was often unavailable, and the intervention was designed to improve estimation of GA, which could potentially bias GA-based analyses. All live births, including multiple births, are included.

Secondary

MeasureTime frameDescription
Use of Antenatal Corticosteroids in Women at Risk of Preterm Birth in All the Study Clusters48 hours after identification of risk for preterm birthAntenatal corticosteroids provided antepartum assessed in women with a less-than-5th-percentile for birth weight infants. Site-specific cut offs were determined from pretrial data.
Suspected Maternal InfectionPregnancy through 6 weeks postpartumMaternal safety was assessed through the frequency of suspected maternal infection, a composite of process outcomes including receipt of antibiotics plus hospital admission or referral, and receipt of intravenous fluids, surgery, or other treatment related to infection. The definition also included evidence of antepartum or post-partum infection for mothers with infants with a birthweight less than 2500 g. Additionally, use of antenatal corticosteroids, neonatal and perinatal mortality, and suspected maternal infection were measured for all births, irrespective of birthweight.
Maternal Mortality RatePregnancy through 42 days postpartumThe denominator for maternal deaths through 42 days is pregnancy ending in live birth + all maternal deaths. Maternal mortality includes all maternal deaths through 42 days postpartum, irrespective of cause.
Neonatal Mortality RateBirth to 28 daysNumber of neonatal deaths before 28 days per 1,000 live births
Stillbirth Mortality Rate20 weeks' gestational age to birthNumber of stillbirths per 1,000 births

Countries

Argentina, Guatemala, India, Kenya, Pakistan, Zambia

Participant flow

Recruitment details

18m, 2-arm, parallel, cluster-randomized trial in 7 Global Network sites from Oct 2011-Mar 2014. Health providers in intervention clusters identified women at high risk of preterm birth for antenatal corticosteroids. Overall, 349 and 360 health facilities served intervention and control clusters, respectively; most (260 in each group) were clinics.

Pre-assignment details

The treatment group for each cluster (and thus all women residing in the cluster) was randomly assigned pretrial (1:1) using a stratified procedure to account for pretrial characteristics. 102 clusters were randomly assigned (51 control:51 intervention). One control cluster withdrew because of unrelated safety concerns prior to study start.

Participants by arm

ArmCount
Intervention Group
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
48
Control Group
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
51
Total99

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyLost to Follow-up1,5011,833
Overall StudyWithdrawal by Subject30
Overall StudyWoman had a miscarriage2117

Baseline characteristics

CharacteristicIntervention GroupControl GroupTotal
Age, Customized
<20
5,412 Participants6,622 Participants12034 Participants
Age, Customized
20-35
41,003 Participants42,938 Participants83941 Participants
Age, Customized
>35
1,741 Participants1,895 Participants3636 Participants
Age, Customized
Missing
63 Participants68 Participants131 Participants
Education
Missing
243 Participants267 Participants510 Participants
Education
No formal schooling
11,005 Participants11,258 Participants22263 Participants
Education
Primary
17,686 Participants19,515 Participants37201 Participants
Education
Secondary
15,528 Participants16,170 Participants31698 Participants
Education
University
3,757 Participants4,313 Participants8070 Participants
Parity
0
16,366 Participants17,901 Participants34267 Participants
Parity
1
13,961 Participants14,599 Participants28560 Participants
Parity
2
17,570 Participants18,934 Participants36504 Participants
Parity
Missing
322 Participants89 Participants411 Participants
Region of Enrollment
Argentina
2,115 participants2,292 participants4407 participants
Region of Enrollment
Guatemala
5,813 participants3,960 participants9773 participants
Region of Enrollment
India
22,398 participants24,227 participants46625 participants
Region of Enrollment
Kenya
5,900 participants7,103 participants13003 participants
Region of Enrollment
Pakistan
7,714 participants8,202 participants15916 participants
Region of Enrollment
Zambia
4,279 participants5,739 participants10018 participants
Sex: Female, Male
Female
48,219 Participants51,523 Participants99742 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 48,6980 / 52,007
serious
Total, serious adverse events
2,932 / 48,6982,774 / 52,007

Outcome results

Primary

Neonatal Mortality Rate at 28 Days in <5th Percentile Birth Weight Infants (as a Proxy Measure for Prematurity)

Neonatal deaths before 28 days per 1,000 live births among \<5th %tile birth weight infants. The \<5th %tile birth weight group was a proxy for preterm. Site-specific cutoffs from pretrial data were 2,450g-Argentina, 2,400g-Zambia, 2,267g-Guatemala, 2,000g-Belgaum, India, 2,150g-Pakistan, 2,000g-Nagpur, India, and 2,500g-Kenya. Infants were classified as \<5th %tile on the basis of measured birth weights. Estimated weights by clinical assessment were used when measured weights were unavailable; those missing weights were classified as \<5th %tile (since based on historical data, most of the missing data were for preterm infants). We used birth weight rather than gestational age (GA) for the primary analysis subgroup because many women in the registry had missing or uncertain GA, ultrasound was often unavailable, and the intervention was designed to improve estimation of GA, which could potentially bias GA-based analyses. All live births, including multiple births, are included.

Time frame: Birth to 28 days

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Intervention GroupNeonatal Mortality Rate at 28 Days in <5th Percentile Birth Weight Infants (as a Proxy Measure for Prematurity)566 Participants
Control GroupNeonatal Mortality Rate at 28 Days in <5th Percentile Birth Weight Infants (as a Proxy Measure for Prematurity)524 Participants
p-value: 0.6595% CI: [0.87, 1.06]t-test, 2 sided
Secondary

Maternal Mortality Rate

The denominator for maternal deaths through 42 days is pregnancy ending in live birth + all maternal deaths. Maternal mortality includes all maternal deaths through 42 days postpartum, irrespective of cause.

Time frame: Pregnancy through 42 days postpartum

Population: All maternal deaths and pregnancy ending in live birth.

ArmMeasureValue (NUMBER)
Intervention GroupMaternal Mortality Rate106 participants
Control GroupMaternal Mortality Rate97 participants
Secondary

Neonatal Mortality Rate

Number of neonatal deaths before 28 days per 1,000 live births

Time frame: Birth to 28 days

Population: All live births, including multiples

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Intervention GroupNeonatal Mortality Rate1300 Participants
Control GroupNeonatal Mortality Rate1211 Participants
p-value: 0.012795% CI: [1.02, 1.22]Generalized linear model with GEE
Secondary

Stillbirth Mortality Rate

Number of stillbirths per 1,000 births

Time frame: 20 weeks' gestational age to birth

Population: All births, including multiples.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Intervention GroupStillbirth Mortality Rate1304 Participants
Control GroupStillbirth Mortality Rate1264 Participants
p-value: 0.018195% CI: [1.02, 1.22]Generalized linear model with GEE
Secondary

Suspected Maternal Infection

Maternal safety was assessed through the frequency of suspected maternal infection, a composite of process outcomes including receipt of antibiotics plus hospital admission or referral, and receipt of intravenous fluids, surgery, or other treatment related to infection. The definition also included evidence of antepartum or post-partum infection for mothers with infants with a birthweight less than 2500 g. Additionally, use of antenatal corticosteroids, neonatal and perinatal mortality, and suspected maternal infection were measured for all births, irrespective of birthweight.

Time frame: Pregnancy through 6 weeks postpartum

Population: Women with infection data available from all data sources

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Intervention GroupSuspected Maternal Infection1,207 Participants
Control GroupSuspected Maternal Infection867 Participants
p-value: <0.000195% CI: [1.33, 1.58]Cochran-Mantel-Haenszel
Secondary

Use of Antenatal Corticosteroids in Women at Risk of Preterm Birth in All the Study Clusters

Antenatal corticosteroids provided antepartum assessed in women with a less-than-5th-percentile for birth weight infants. Site-specific cut offs were determined from pretrial data.

Time frame: 48 hours after identification of risk for preterm birth

Population: Among women with a less-than-5th-percentile for birth weight infant and with data on administration of antenatal corticosteroid data available.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Intervention GroupUse of Antenatal Corticosteroids in Women at Risk of Preterm Birth in All the Study Clusters1,052 Participants
Control GroupUse of Antenatal Corticosteroids in Women at Risk of Preterm Birth in All the Study Clusters215 Participants
Comparison: The trial was powered to detect a 30% reduction in 28-day neonatal mortality among infants born at less than the 5th percentile of birth weight, based on previous research and an expected increase from 10% to 50% in the use of antenatal corticosteroids among women at risk of preterm birth in the intervention group.p-value: <0.000195% CI: [0.3299, 0.3792]Cochran-Mantel-Haenszel

Source: ClinicalTrials.gov · Data processed: Mar 19, 2026