The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial: A multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries to improve newborn outcomes

• Register: ANZCTR
• Last refreshed on: 29 March 2021
• Main ID: ACTRN12617000476336
• Date of registration: 31/03/2017
• Prospective Registration: Yes
• Primary sponsor: World Health Organization
• Public title: The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial: A multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries to improve newborn outcomes
• Scientific title: WHO ACTION-I Trial: A multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries to improve newborn outcomes
• Date of first enrolment: 24/12/2017
• Target sample size: 6018
• Recruitment status: Stopped early
• URL: https://anzctr.org.au/ACTRN12617000476336.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 3

Countries of recruitment

Bangladesh, India, Kenya, Nigeria, Pakistan

Contacts

• Name: Dr Olufemi T. Oladapo

• Name: Dr Olufemi T. Oladapo

Key inclusion & exclusion criteria

Inclusion criteria: - Birth planned or expected within 48 hours
- Gestational age from 26 weeks 0 days to 33 weeks 6 days (see Figure 3)
- Women with singleton or multiple pregnancies, where the fetus(es) is(are) alive
- Women with no clinical signs of severe infection (as per clinical assessment)
- Women willing and able to provide consent (or if a minor, provides assent and guardian provides consent)

Exclusion criteria: 1. Intrauterine fetal death
2. Major or lethal congenital fetal anomaly identified
3. Clinical suspicion or evidence of clinical chorioamnionitis, as per obstetric care physician assessment
4. Clinical suspicion or evidence of severe infection, as per obstetric care physician assessment
5. No prior ultrasound-based estimate of gestational age available and immediate ultrasound examination is not possible
6. Any concurrent or recent (within the past 2 weeks) systemic corticosteroid use during the current pregnancy (outside of trial)
7. Unwilling or unable to provide consent
8. Currently a participant in another clinical trial related to maternal and neonatal health
9. Any other clinical indication where the treating clinician considers corticosteroids to be contraindicated


Age minimum: No limit
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Reproductive Health and Childbirth - Complications of newborn

preterm birth;
preterm birth

Intervention(s)

Antenatal corticosteroids (Dexamethasone IM)

The drug regimen for this trial is aligned with the WHO recommendations on use of antenatal corticosteroids. The intervention regimen will be:
- A single course of 6mg dexamethasone by intramuscular injection, administered every 12 hours, to a total of four (4) doses (time points 0 hours, 12 hours, 24 hours and 36 hours)
- If the full regimen is completed, the woman would have received a total of 24mg in divided doses
- If a woman has not delivered within 7 completed days after completion of the first course, is re-assessed as eligible (if the gestational age is still less than 34 weeks), and a subsequent clinical assessment demonstrates that birth is planned or expected in the next 48 hours, a second course according to the regimen described above will be administered. Hence, the use of a repeat course in eligible women shall be the same as the initial allocation (i.e. women initially randomized to dexamethasone will only receive dexamethasone as repeat course).

No further repeat courses will be used (i.e. a maximum of two courses per participant).

Adherence will be monitored through documenting number of injections administered to each participant.

Primary Outcome(s)

Neonatal death
[birth to 28 completed days of life]

Possible maternal bacterial infection (Occurrence of maternal fever, or clinically suspected or confirmed infection, for which therapeutic antibiotics were used)[Randomization to 28 days postpartum (during hospital admission only)
]

Stillbirth or neonatal death[Any death of a fetus (post enrolment) or death of a live birth, from randomization to 28 completed days of life ]

Secondary Outcome(s)

Length of total maternal hospitalization for birth (days), measured through use of medical records[Randomization to 28 days postpartum (during hospitalization only)]

Neonatal sepsis (clinical diagnosis, made by clinical assessment of neonatal care physician)[during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first)]

Timing to full enteral feeding, assessed in medical record.[birth to start of full enteral feeding (whichever comes first)]

Total number of treatment (dexamethasone or placebo) doses received, through research assistants recording number of doses administered.[Randomization until birth]

Use of oxygen therapy (reported as any use, and length of use in days) measured through use of medical records and direct observation of newborn. [during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first)]

Any use of antibiotics in an enrolled participant (maternal) while in facility (prophylactic or therapeutic) measured through use of medical records[Randomization to 28 days postpartum (during hospitalization only)]

Major neonatal resuscitation at birth (The use of positive pressure ventilation for more than one minute), assessed in medical record [immediate postnatal period]

Postpartum endometritis (suspected or confirmed), based on clinical assessment by obstetric care physician[Randomization to 28 days postpartum (during postpartum admission/s only)]

continuous positive airway pressure (CPAP) ventilation (reported as any use, length of use in days), measured through use of medical records and direct observation of newborn. [during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first)]

Length of newborn's hospital stay after birth, measured through use of medical records [birth to 28 days of life (initial hospitalization only)]

Any maternal referral to another facility, measured through use of medical records[Randomization to 28 days postpartum (during hospitalization only)]

Admission of newborn to a special newborn care unit (SCU) (reported as any admission, length of admission), measured through use of medical records[birth to 28 days of life (during initial hospitalization only)]

Maternal fever (greater than or equal to 38.0 C ) as measured using calibrated thermometer[Randomization to 28 days postpartum (during hospital admission/s only)]

Severe respiratory distress of neonate (based on clinical features and SpO2 level <90% or use of supplemental oxygen) (overall; and at 24 hours) [during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first) ]

Compliance with study allocation, through research assistants recording number of doses administered.[Randomization until birth]

Maternal readmission for healthcare at facility (reported as any readmission, length of stay, number of readmissions, and cause of readmission) measured through use of medical records[Randomization to 28 days postpartum (during hospitalization only)]

Use of repeat course (treatment or placebo), through research assistants recording number of doses administered.[Randomization until birth]

Maternal death[randomization to 28 days postpartum]

Neonatal hypoglycemia is defined as blood glucose measure less than 45 mg/dl (2.6mmol/l) (overall, and at 6 and 36 hours)[during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first) ]

Time from initiation of first dose until birth, through research assistants recording number and timing of doses administered. [Randomization until birth]

Newborn readmission for healthcare at facility (reported as any readmission, length of stay, number of readmissions, and cause of readmission) measured through use of medical records[birth to 28 days of life]

Non-obstetric infection (suspected or confirmed), based on clinical assessment by obstetric care physician[Randomization to 28 days postpartum (during hospital admission/s only)]

Severe intraventricular haemorrhage (sIVH) (assessed using transcranial ultrasound at Day 7 of life or discharge, whichever comes first). [birth, up to 7 days of life or discharge (whichever comes first)]

Stillbirth [randomization to birth]

Surfactant treatment (reported as any use, and total number of doses) measured through use of medical records and direct observation of newborn[during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first)]

Wound infection (suspected or confirmed), based on clinical assessment by obstetric care physician[Randomization to 28 days postpartum (during postpartum admission/s only)]

Apgar score <7 at 5 minutes[first 5 minutes of life]

Chorioamnionitis (suspected or confirmed), based on clinical assessment by obstetric care physician[Randomization to birth]

Early neonatal death [birth to 7 completed days of life]

Maternal therapeutic antibiotic use (reported as a any therapeutic antibiotic use, and number of days of therapeutic antibiotic use) measured through use of medical records[randomization to 28 days postpartum (during hospitalization only)]

Mechanical ventilation (MV) (reported as any use of MV during admission. and length of use in days) measured through use of medical records and direct observation of newborn. .
[during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first)]

Timing of breast milk feeding initiation (Timing of initiation of breast milk feeding in hours after birth (breastfeeding, cup or tube feeding), assessed in medical record or maternal report.[birth to start of breast milk feeding (whichever comes first)]

Use of therapeutic antibiotics (intravenous or intramuscular) for 5 or more days (reported as any use and length of use) measured through use of medical records and direct observation of newborn.
[during initial postnatal hospitalization only, until death, discharge or completed 7 days (whichever comes first)]

Secondary ID(s)

A65913

Source(s) of Monetary Support

Bill and Melinda Gates Foundation

Secondary Sponsor(s)

University of Nairobi, Nairobi, Kenya

Kenyatta National Hospital

Aga Khan University

KLE University’s Jawaharlal Nehru Medical College

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

International Center for Maternal and Newborn Health

Obafemi Awolowo University

University of Ibadan

Ethics review

Status: Approved
Approval date: 20/02/2017
Contact:

WHO Ethics Review Committee

Results

• Results available: Yes
• Date Posted: 22/03/2021
• Date Completed: 20/02/2020