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| Name | Class |
|---|---|
| RTI International | OTHER |
| Tulane University School of Medicine | OTHER |
| Institute for Clinical Effectiveness and Health Policy | OTHER |
| University of Alabama at Birmingham |
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Multi-country two-arm, parallel cluster randomized controlled trial to reduce neonatal mortality through increasing the rate of antenatal corticosteroid administration to eligible women.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Active Comparator | Eligible women at high risk for preterm birth will be identified and four 6 mg doses of dexamethasone will be administered before delivery. |
|
| Control | No Intervention | Control arm will not receive a specific intervention for comparison. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Increasing use of Antenatal Corticosteroids (ACS) | Behavioral | Intervention clusters:
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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Birth to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 48 hours after identification of risk for preterm birth |
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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
Participant-level inclusion criteria include all pregnant women living in and delivering in the study cluster who:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fernando Althabe, M.D. | Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Clinical Effectiveness and Health Policy (IECS) | Buenos Aires | Argentina | ||||
| Universidad Francisco Marroquin Facultad de Medicina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33368142 | Derived | McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020 Dec 25;12(12):CD004454. doi: 10.1002/14651858.CD004454.pub4. | |
| 32452555 | Derived | Rohwer AC, Oladapo OT, Hofmeyr GJ. Strategies for optimising antenatal corticosteroid administration for women with anticipated preterm birth. Cochrane Database Syst Rev. 2020 May 26;5(5):CD013633. doi: 10.1002/14651858.CD013633. |
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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.
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.
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Women enrolled in the Global Network Maternal Newborn Health Registry (MNHR) during the Antenatal Corticosteroid Trial period with delivery and outcome data available from MNHR.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | Birth to 28 days |
|
During the period that the trial was active in a particular cluster, serious adverse events were captured on each woman from the time the woman was enrolled in the MNH registry until 6 weeks after delivery for each pregnant woman enrolled in the MNH registry and her babies.
Total number of serious adverse events is out of all participants (i.e. the number of women plus the number of babies (stillbirths and live births)).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Maternal death | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elizabeth McClure, Data Coordinating Center PI | NICHDGlobal | 919-316-3773 | mcclure@rti.org |
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| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| OTHER |
| University Teaching Hospital, Lusaka, Zambia | OTHER |
| University of Colorado, Denver | OTHER |
| Universidad Francisco MarroquÃn | OTHER |
| Jawaharlal Nehru Medical College | OTHER |
| Christiana Care Health Services | OTHER |
| Aga Khan University | OTHER |
| Columbia University | OTHER |
| Indiana University | OTHER |
| Moi Univeristy | OTHER |
| Lata Medical Research Foundation, Nagpur | OTHER |
| Massachusetts General Hospital | OTHER |
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|
|
| 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. |
| Pregnancy through 6 weeks postpartum |
| 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. | Pregnancy through 42 days postpartum |
| Neonatal Mortality Rate | Number of neonatal deaths before 28 days per 1,000 live births | Birth to 28 days |
| Stillbirth Mortality Rate | Number of stillbirths per 1,000 births | 20 weeks' gestational age to birth |
| Guatemala City |
| Guatemala |
| JN Medical College | Belagavi | India |
| Lata Medical Research Foundation | Nagpur | India |
| Moi University School of Medicine | Eldoret | Kenya |
| Aga Khan University | Karachi | Pakistan |
| University of Zambia | Lusaka | Zambia |
| 28927395 | Derived | Patel A, Prakash AA, Pusdekar YV, Kulkarni H, Hibberd P. Detection and risk stratification of women at high risk of preterm birth in rural communities near Nagpur, India. BMC Pregnancy Childbirth. 2017 Sep 19;17(1):311. doi: 10.1186/s12884-017-1504-4. |
| 27255082 | Derived | Goldenberg RL, Thorsten VR, Althabe F, Saleem S, Garces A, Carlo WA, Pasha O, Chomba E, Goudar S, Esamai F, Krebs NF, Derman RJ, Liechty EA, Patel A, Hibberd PL, Buekens PM, Koso-Thomas M, Miodovnik M, Jobe AH, Wallace DD, Belizan JM, McClure EM. The global network antenatal corticosteroids trial: impact on stillbirth. Reprod Health. 2016 Jun 2;13(1):68. doi: 10.1186/s12978-016-0174-4. |
| 27228986 | Derived | Berrueta M, Hemingway-Foday J, Thorsten VR, Goldenberg RL, Carlo WA, Garces A, Patel A, Saleem S, Pasha O, Chomba E, Hibberd PL, Krebs NF, Goudar S, Derman RJ, Esamai F, Liechty EA, Moore JL, McClure EM, Koso-Thomas M, Buekens PM, Belizan JM, Althabe F. Use of antenatal corticosteroids at health facilities and communities in low-and-middle income countries. Reprod Health. 2016 May 27;13(1):66. doi: 10.1186/s12978-016-0176-2. |
| 27221319 | Derived | Klein K, McClure EM, Colaci D, Thorsten V, Hibberd PL, Esamai F, Garces A, Patel A, Saleem S, Pasha O, Chomba E, Carlo WA, Krebs NF, Goudar S, Derman RJ, Liechty EA, Koso-Thomas M, Buekens PM, Belizan JM, Goldenberg RL, Althabe F. The Antenatal Corticosteroids Trial (ACT): a secondary analysis to explore site differences in a multi-country trial. Reprod Health. 2016 May 24;13(1):64. doi: 10.1186/s12978-016-0179-z. |
| 27221237 | Derived | Garces A, McClure EM, Figueroa L, Pineda S, Hambidge KM, Krebs NF, Thorsten VR, Wallace DD, Althabe F, Goldenberg RL. A multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth: a case study from the Guatemalan Western Highlands. Reprod Health. 2016 May 24;13(1):63. doi: 10.1186/s12978-016-0178-0. |
| 25458726 | Derived | Althabe F, Belizan JM, McClure EM, Hemingway-Foday J, Berrueta M, Mazzoni A, Ciganda A, Goudar SS, Kodkany BS, Mahantshetti NS, Dhaded SM, Katageri GM, Metgud MC, Joshi AM, Bellad MB, Honnungar NV, Derman RJ, Saleem S, Pasha O, Ali S, Hasnain F, Goldenberg RL, Esamai F, Nyongesa P, Ayunga S, Liechty EA, Garces AL, Figueroa L, Hambidge KM, Krebs NF, Patel A, Bhandarkar A, Waikar M, Hibberd PL, Chomba E, Carlo WA, Mwiche A, Chiwila M, Manasyan A, Pineda S, Meleth S, Thorsten V, Stolka K, Wallace DD, Koso-Thomas M, Jobe AH, Buekens PM. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial. Lancet. 2015 Feb 14;385(9968):629-639. doi: 10.1016/S0140-6736(14)61651-2. Epub 2014 Oct 15. |
| 22992312 | Derived | Althabe F, Belizan JM, Mazzoni A, Berrueta M, Hemingway-Foday J, Koso-Thomas M, McClure E, Chomba E, Garces A, Goudar S, Kodkany B, Saleem S, Pasha O, Patel A, Esamai F, Carlo WA, Krebs NF, Derman RJ, Goldenberg RL, Hibberd P, Liechty EA, Wright LL, Bergel EF, Jobe AH, Buekens P. Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol. Reprod Health. 2012 Sep 19;9:22. doi: 10.1186/1742-4755-9-22. |
| Woman had a miscarriage |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Education | Count of Participants | Participants |
|
| Parity | Count of Participants | Participants |
|
| OG000 | 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. |
| OG001 | 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. |
|
|
|
| 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. | Among women with a less-than-5th-percentile for birth weight infant and with data on administration of antenatal corticosteroid data available. | Posted | Count of Participants | Participants | 48 hours after identification of risk for preterm birth |
|
|
|
|
| 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. | Women with infection data available from all data sources | Posted | Count of Participants | Participants | Pregnancy through 6 weeks postpartum |
|
|
|
|
| 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. | All maternal deaths and pregnancy ending in live birth. | Posted | Number | participants | Pregnancy through 42 days postpartum |
|
|
|
| Secondary | Neonatal Mortality Rate | Number of neonatal deaths before 28 days per 1,000 live births | All live births, including multiples | Posted | Count of Participants | Participants | Birth to 28 days |
|
|
|
|
| Secondary | Stillbirth Mortality Rate | Number of stillbirths per 1,000 births | All births, including multiples. | Posted | Count of Participants | Participants | 20 weeks' gestational age to birth |
|
|
|
|
| 2,932 |
| 48,698 |
| 0 |
| 48,698 |
| EG001 | 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. | 2,774 | 52,007 | 0 | 52,007 |
| Stillbirth/neonatal death | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Congenital anomaly | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
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| D000091642 | Urogenital Diseases |
| Superiority |
Descriptive analysis.