The World Health Organization Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns (ACTION-III) Trial: study protocol for a multi-country, multi-centre, double-blind, three-arm, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at high probability of late preterm birth in hospitals in low- resource countries

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2024年4月12日

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Temitope Adesiji Adegboyega,
Ebunoluwa Aderonke Adejuyigbe,
Olubukola Adeponle Adesina,
Babalola Adeyemi,
Salahuddin Ahmed,
Francis Akinkunmi,
Jalemba Aluvaala,
Henry Anyabolu,
Shabina Ariff,
Sugandha Arya,
Ibraheem Awowole,
Adejumoke Idowu Ayede,
Neelofur Babar,
Sumitra Bachani,
Rajiv Bahl,
Abdullah H. Baqui,
Harish Chellani,
Saleha Begum Chowdhury,
Lynn M. Coppola,
Simon Cousens,
Pradeep K. Debata,
Ayesha de Costa,
Sangappa M. Dhaded,
Kasturi V. Donimath,
Adegoke Gbadegesin Falade,
Shivaprasad S. Goudar,
Shuchita Gupta,
George N. Gwako,
Theresa Azonima Irinyenikan,
Dennis Anthony Isah,
Nigar Jabeen,
Arshia Javed,
Naima T. Joseph,
Rasheda Khanam,
John Kinuthia,
Oluwafemi Kuti,
Tina Lavin,
Ahmed R. Laving,
Sandhya Maranna,
Nicole Minckas,
Pratima Mittal,
Diwakar Mohan,
Sidrah Nausheen,
My Huong Nguyen,
Olufemi T. Oladapo,
Olanike Abosede Olutekunbi,
Rosena Olubanke Oluwafemi,
Alfred Osoti,
Yeshita V. Pujar,
Zahida P. Qureshi,
Suman P. N. Rao,
Sophie Sarrassat,
M. A. Shahed,
Mohammod Shahidullah,
Lumaan Sheikh,
Manjunath S. Somannavar,
Sajid Soofi,
Jyotsna Suri,
Sunil S. Vernekar,
Joshua P. Vogel,
Nitya Wadhwa,
Prakash K. Wari,
Fred Were,
Blair J. Wylie

摘要

Background

Preterm birth complications are the leading cause of newborn and under-5 mortality. Over 85% of all preterm births occur in the late preterm period, i.e. between 34 and < 37 weeks of gestation. Antenatal corticosteroids (ACS) prevent mortality and respiratory morbidity when administered to women at high risk of an early preterm birth, i.e. < 34 weeks’ gestation. However, the benefits and risks of ACS in the late preterm period are less clear; both guidelines and practices vary between settings. Emerging evidence suggests that the benefits of ACS may be achievable at lower doses than presently used. This trial aims to determine the efficacy and safety of two ACS regimens compared to placebo, when given to women with a high probability of late preterm birth, in hospitals in low-resource countries.

Methods

WHO ACTION III trial is a parallel-group, three-arm, individually randomized, double-blind, placebo-controlled trial of two ACS regimens: dexamethasone phosphate 4 × 6 mg q12h or betamethasone phosphate 4 × 2 mg q 12 h. The trial is being conducted across seven sites in five countries—Bangladesh, India, Kenya, Nigeria, and Pakistan. Eligible women are those with a gestational age between 34 weeks 0 days and 36 weeks 5 days, who have a high probability of preterm birth between 12 h and 7 days (up to 36 weeks 6 days gestation). The primary outcome is a composite of stillbirth or neonatal death within 72 h of birth or use of newborn respiratory support within 72 h of birth or prior to discharge from hospital, whichever is earlier. Secondary outcomes include safety and health utilization measures for both women and newborns. The sample size is 13,500 women.

Discussion

This trial will evaluate the benefits and possible harms of ACS when used in women likely to have a late preterm birth. It will also evaluate a lower-dose ACS regimen based on literature from pharmacokinetic studies. The results of this trial will provide robust critical evidence on the safe and appropriate use of ACS in the late preterm period internationally.

Trial registration

ISRCTN11434567. Registered on 7 June 2021.