{ "release_id": "15708f235d73cd42", "id": "maternal:action-i-trial", "owner": "maternal", "kind": "study", "slug": "action-i-trial", "name": "WHO ACTION-I trial", "aliases": [ "ACTION-I", "WHO ACTION-I Trial" ], "atlases": [ "maternal" ], "summary_plain": "A trial in 29 hospitals in Bangladesh, India, Kenya, Nigeria and Pakistan. Pregnant women who were likely to give birth early received either a dexamethasone steroid injection or a dummy injection, to see whether the steroid lowered newborn deaths. The trial stopped early because deaths among the babies were lower in the dexamethasone group.", "summary_technical": "Multicountry, multicentre, individually randomized, parallel-group, double-blind, placebo-controlled trial (ACTRN12617000476336; CTRI/2017/04/008326). 2852 women and their 3070 fetuses were randomized; registry targets were 6018 (ANZCTR) and 6120 (CTRI, via ICTRP). Entry: gestational age 26 weeks 0 days to 33 weeks 6 days with birth planned or expected within 48 hours. Intramuscular dexamethasone 6 mg every 12 hours for up to four doses against identical placebo. Primary outcomes: neonatal death, stillbirth or neonatal death, and possible maternal bacterial infection, tested for non-inferiority with a margin of 1.25 on the relative scale. The data safety monitoring board recommended stopping after the second interim analysis, and recruitment stopped on 21 November 2019. The registries differ on first enrolment: the ICTRP view of the CTRI record lists 2017-06-01 (read as day-month-year), the same date as ANZCTR's anticipated first enrolment, while ANZCTR's actual first enrolment is 2017-12-24 and the manuscript says women were randomized from December 2017. Sponsor: WHO. The manuscript names the Gates Foundation as primary funder with additional support from WHO departments; the PubMed abstract credits both.", "editorial_state": "draft", "last_substantive_edit": "2026-10-12", "last_evidence_check": null, "next_review_due": null, "external_ids": [ { "namespace": "anzctr", "value": "ACTRN12617000476336" }, { "namespace": "ctri", "value": "CTRI/2017/04/008326" } ], "navigation": { "maternal": { "life-stage": [ "pregnancy", "newborn" ] } }, "payload": { "design": "Multicountry, multicentre, individually randomized (1:1, site-stratified), parallel-group, double-blind, placebo-controlled trial of intramuscular dexamethasone against identical placebo, given to women at risk of imminent preterm birth in 29 secondary- and tertiary-level hospitals. Women were randomized from December 2017 through November 2019. The sources describe the block design differently, and this is not reconciled: the manuscript says \"balanced permuted blocks of size 10\", while the CTRI record read through ICTRP describes permuted blocks of variable size.", "drug_phase": "3", "registry_statuses": [ { "status": "Stopped early", "snapshot": "maternal:anzctr-actrn12617000476336-2026-10-11" }, { "status": "Completed", "snapshot": "maternal:ictrp-ctri-2017-04-008326-2026-10-11" } ], "start_date": { "date": "2017-12-24", "type": "actual", "snapshot": "maternal:anzctr-actrn12617000476336-2026-10-11" }, "primary_completion_date": null, "completion_date": null, "countries": [ { "code": "BD", "snapshot": "maternal:pmc-pmc7660991-2026-10-11" }, { "code": "IN", "snapshot": "maternal:pmc-pmc7660991-2026-10-11" }, { "code": "KE", "snapshot": "maternal:pmc-pmc7660991-2026-10-11" }, { "code": "NG", "snapshot": "maternal:pmc-pmc7660991-2026-10-11" }, { "code": "PK", "snapshot": "maternal:pmc-pmc7660991-2026-10-11" } ], "care_setting": { "description": "Hospital-based care at 29 secondary- and tertiary-level hospitals across six study sites. The hospitals were chosen after a standard assessment so that the WHO conditions for antenatal corticosteroid use could reasonably be met.", "snapshot": "maternal:pmc-pmc7660991-2026-10-11" }, "stopped_early": { "scope": "enrollment", "date": "2019-11-21", "reason": "After the second interim analysis the data safety monitoring board recommended stopping the trial for benefit on infant mortality, and recruitment stopped at all sites on this date. ANZCTR records the status as stopped early; the CTRI record, read through ICTRP, says completed.", "snapshot": "maternal:pmc-pmc7660991-2026-10-11" }, "enrollment": [ { "count": 2852, "basis": "randomized", "unit": "women", "snapshot": "maternal:pubmed-33095526-2026-10-11" }, { "count": 3070, "basis": "randomized", "unit": "fetuses", "snapshot": "maternal:pubmed-33095526-2026-10-11" }, { "count": 6018, "basis": "planned", "unit": "women (ANZCTR target sample size)", "snapshot": "maternal:anzctr-actrn12617000476336-2026-10-11" }, { "count": 6120, "basis": "planned", "unit": "participants (CTRI target sample size via ICTRP; the unit is not named)", "snapshot": "maternal:ictrp-ctri-2017-04-008326-2026-10-11" }, { "count": 2852, "basis": "enrolled", "unit": "participants (ANZCTR final sample size under accrual; the unit is not named)", "snapshot": "maternal:anzctr-actrn12617000476336-2026-10-11" } ], "arms": [ { "id": "maternal:action-i-trial-arm-dexamethasone", "label": "Dexamethasone (intervention)", "intervention": "maternal:antenatal-corticosteroids", "description": "Intramuscular dexamethasone 6 mg given to the woman every 12 hours, up to four doses or until hospital discharge or birth. A repeat course with the same allocation was allowed if she had not given birth after seven completed days and still met the inclusion criteria." }, { "id": "maternal:action-i-trial-arm-placebo", "label": "Identical placebo (control)", "intervention": null, "description": "Identical placebo (normal saline per ANZCTR) on the same schedule as dexamethasone, with the same repeat-course rule." } ], "findings": [ { "id": "maternal:f-action-i-neonatal-death-dexamethasone", "outcome_id": "maternal:outcome-neonatal-death-28d", "context_id": "maternal:ctx-action-i-liveborn-infants", "arm_id": "maternal:action-i-trial-arm-dexamethasone", "comparator_arm_id": null, "claim_id": "maternal:claim-action-i-neonatal-death", "snapshot_id": "maternal:pmc-pmc7660991-2026-10-11", "endpoint_role": "primary", "effect_measure": "liveborn infants who died by 28 completed days of life (count)", "numeric_value": 278, "reported_text": "278/1417 (19.6)", "unit": "infants", "denominator": 1417, "denominator_status": null, "denominator_basis": "Liveborn infants in this group, as reported in Table 2 of the Author Final Manuscript; not checked against the version of record.", "time_window": "Birth to 28 completed days of life", "estimate_lower": null, "estimate_upper": null, "interval_method": null, "interval_status": "not_applicable" }, { "id": "maternal:f-action-i-neonatal-death-placebo", "outcome_id": "maternal:outcome-neonatal-death-28d", "context_id": "maternal:ctx-action-i-liveborn-infants", "arm_id": "maternal:action-i-trial-arm-placebo", "comparator_arm_id": null, "claim_id": "maternal:claim-action-i-neonatal-death", "snapshot_id": "maternal:pmc-pmc7660991-2026-10-11", "endpoint_role": "primary", "effect_measure": "liveborn infants who died by 28 completed days of life (count)", "numeric_value": 331, "reported_text": "331/1406 (23.5)", "unit": "infants", "denominator": 1406, "denominator_status": null, "denominator_basis": "Liveborn infants in this group, as reported in Table 2 of the Author Final Manuscript; not checked against the version of record.", "time_window": "Birth to 28 completed days of life", "estimate_lower": null, "estimate_upper": null, "interval_method": null, "interval_status": "not_applicable" }, { "id": "maternal:f-action-i-neonatal-death-rr", "outcome_id": "maternal:outcome-neonatal-death-28d", "context_id": "maternal:ctx-action-i-liveborn-infants", "arm_id": "maternal:action-i-trial-arm-dexamethasone", "comparator_arm_id": "maternal:action-i-trial-arm-placebo", "claim_id": "maternal:claim-action-i-neonatal-death", "snapshot_id": "maternal:pmc-pmc7660991-2026-10-11", "endpoint_role": "primary", "effect_measure": "relative risk, dexamethasone vs placebo, modelled with adjustment for study site and for clustering from multiple births (Table 2 footnote)", "numeric_value": 0.84, "reported_text": "0.84 (0.72-0.97)", "unit": "ratio", "denominator": null, "denominator_status": "not_applicable", "denominator_basis": "Comparison of the two per-arm rows above", "time_window": "Birth to 28 completed days of life", "estimate_lower": 0.72, "estimate_upper": 0.97, "interval_method": "95% confidence interval, adjusted for multiplicity (Table 2 footnote)", "interval_status": null } ] }, "content_digest": "2345b168518236d31f82d933ef4083442a3a46c7af8f85b02df3088bf83ebc48", "review": { "content_digest": "2345b168518236d31f82d933ef4083442a3a46c7af8f85b02df3088bf83ebc48", "current": [], "conflicting": [], "stale": [], "inactive": [] }, "claims": [ { "release_id": "15708f235d73cd42", "id": "maternal:claim-action-i-stopped-early", "owner": "maternal", "subject_entity_id": "maternal:action-i-trial", "category": "descriptive", "statement": "ACTION-I stopped recruiting women early. After the second interim analysis the data safety monitoring board recommended stopping the trial because deaths among infants were lower with dexamethasone, and recruitment stopped at all sites on 21 November 2019. The two registries disagree on the trial's status: ANZCTR records it as stopped early and the CTRI record, read through WHO ICTRP, as completed.", "context": { "id": "maternal:ctx-action-i-women-26w0d-33w6d", "label": "Pregnant women at risk of imminent preterm birth at 26w0d to 33w6d, in 29 hospitals in five low-resource countries (ACTION-I)", "recipient": "maternal", "population": "Pregnant women with a confirmed live fetus, single or multiple pregnancy, who were at risk of preterm birth between 26 weeks 0 days and 33 weeks 6 days of gestation and whose birth was planned or expected within 48 hours. Gestational age came from the earliest ultrasound or one done at admission.", "care_setting": "Hospital-based: 29 secondary- and tertiary-level hospitals across six study sites. The hospitals were chosen after a standard assessment so that the WHO conditions for antenatal corticosteroid use could reasonably be met.", "geography": "Bangladesh, India, Kenya, Nigeria and Pakistan", "life_stage": "Pregnancy, from randomization to birth, with maternal infection followed to 28 days after birth", "gestational_age_min_days": 182, "gestational_age_max_days": 237, "postnatal_age_min_days": null, "postnatal_age_max_days": null, "gestational_age_status": null, "postnatal_age_status": null, "followup_description": "The maternal primary outcome, possible maternal bacterial infection, ran from randomization to 28 days postpartum and was captured during hospital admission only.", "eligibility": { "inclusion": [ "Live fetus, single or multiple pregnancy", "Gestational age 26 weeks 0 days to 33 weeks 6 days", "Birth planned or expected in the next 48 hours", "Written informed consent before randomization" ], "exclusion": [ "Clinical signs of severe infection", "Major congenital fetal anomalies", "Systemic glucocorticoid use now or within the past two weeks", "Participation in another trial", "Contraindication to steroids", "Clinical suspicion or evidence of chorioamnionitis (registry criteria only; the paper lists clinical signs of severe infection)", "No earlier ultrasound estimate of gestational age and an immediate ultrasound not possible (registry criteria only; both ANZCTR and CTRI via ICTRP list it, and the paper says gestational age came from the earliest ultrasound or one done at admission)" ] } }, "evidence_stage": "not_applicable", "certainty": "not_assessed", "certainty_method": null, "limitations": "The registry disagreement is recorded, not reconciled. The CTRI view is a WHO ICTRP mirror refreshed in November 2021, and the primary CTRI record could not be read.", "editorial_state": "draft", "checked_at": null, "next_review_due": null, "valid_from": null, "valid_to": null, "citations": [ { "evidence_role": "supports", "locator": "Abstract, RESULTS, sentence 2", "applicability_note": "Abstract of the primary report.", "snapshot": { "id": "maternal:pubmed-33095526-2026-10-11", "retrieved_at": "2026-10-11T19:10:30Z", "content_hash": "adb2579c89c865461eb3f3ace681a011868a4f43b15a028d7178d08ad0d7057e", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "maternal:action-i-nejm-2020", "source_type": "publication", "title": "Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries", "canonical_url": "https://doi.org/10.1056/NEJMoa2022398", "identifier_namespace": "doi", "identifier_value": "10.1056/NEJMoa2022398", "publication_date": "2020-12-24", "publisher": "Massachusetts Medical Society (N Engl J Med 383(26):2514-2525)", "edition": "Version of record not fetched (HTTP 403 on 2026-10-11). The abstract comes from PubMed and the bibliographic data from Crossref. Full-text facts come from the PMC Author Final Manuscript PMC7660991. Tables and figures were read in that manuscript and not checked against the version of record. PubMed lists comments and letters on the article but no erratum or retraction.", "reuse_basis": "Bibliographic metadata and short factual extraction. The PMC Author Final Manuscript states that it is licensed for use under the CC BY license and is committed at research/snapshots/ma-pmc-PMC7660991.xml. Attribution: WHO ACTION Trials Collaborators, N Engl J Med 2020;383:2514-2525, doi:10.1056/NEJMoa2022398, Author Final Manuscript via PMC (PMC7660991). The version of record is not redistributed.", "public_text": "quote" } }, { "evidence_role": "supports", "locator": "Methods, Statistical analysis, para 3: board recommendation", "applicability_note": "Author Final Manuscript (CC BY); not checked against the version of record.", "snapshot": { "id": "maternal:pmc-pmc7660991-2026-10-11", "retrieved_at": "2026-10-11T19:10:31Z", "content_hash": "8c795f040d84bf82311862509bdde4ea0f243d2933f596c1bd4f80ebdae14b26", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "maternal:action-i-nejm-2020", "source_type": "publication", "title": "Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries", "canonical_url": "https://doi.org/10.1056/NEJMoa2022398", "identifier_namespace": "doi", "identifier_value": "10.1056/NEJMoa2022398", "publication_date": "2020-12-24", "publisher": "Massachusetts Medical Society (N Engl J Med 383(26):2514-2525)", "edition": "Version of record not fetched (HTTP 403 on 2026-10-11). The abstract comes from PubMed and the bibliographic data from Crossref. Full-text facts come from the PMC Author Final Manuscript PMC7660991. Tables and figures were read in that manuscript and not checked against the version of record. PubMed lists comments and letters on the article but no erratum or retraction.", "reuse_basis": "Bibliographic metadata and short factual extraction. The PMC Author Final Manuscript states that it is licensed for use under the CC BY license and is committed at research/snapshots/ma-pmc-PMC7660991.xml. Attribution: WHO ACTION Trials Collaborators, N Engl J Med 2020;383:2514-2525, doi:10.1056/NEJMoa2022398, Author Final Manuscript via PMC (PMC7660991). The version of record is not redistributed.", "public_text": "quote" } }, { "evidence_role": "supports", "locator": "Methods, Statistical analysis, para 3: recruitment stop", "applicability_note": "Author Final Manuscript (CC BY); not checked against the version of record.", "snapshot": { "id": "maternal:pmc-pmc7660991-2026-10-11", "retrieved_at": "2026-10-11T19:10:31Z", "content_hash": "8c795f040d84bf82311862509bdde4ea0f243d2933f596c1bd4f80ebdae14b26", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "maternal:action-i-nejm-2020", "source_type": "publication", "title": "Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries", "canonical_url": "https://doi.org/10.1056/NEJMoa2022398", "identifier_namespace": "doi", "identifier_value": "10.1056/NEJMoa2022398", "publication_date": "2020-12-24", "publisher": "Massachusetts Medical Society (N Engl J Med 383(26):2514-2525)", "edition": "Version of record not fetched (HTTP 403 on 2026-10-11). The abstract comes from PubMed and the bibliographic data from Crossref. Full-text facts come from the PMC Author Final Manuscript PMC7660991. Tables and figures were read in that manuscript and not checked against the version of record. PubMed lists comments and letters on the article but no erratum or retraction.", "reuse_basis": "Bibliographic metadata and short factual extraction. The PMC Author Final Manuscript states that it is licensed for use under the CC BY license and is committed at research/snapshots/ma-pmc-PMC7660991.xml. Attribution: WHO ACTION Trials Collaborators, N Engl J Med 2020;383:2514-2525, doi:10.1056/NEJMoa2022398, Author Final Manuscript via PMC (PMC7660991). The version of record is not redistributed.", "public_text": "quote" } }, { "evidence_role": "supports", "locator": "Recruitment, Reason for early stopping", "applicability_note": "ANZCTR record as last updated 2021-03-22.", "snapshot": { "id": "maternal:anzctr-actrn12617000476336-2026-10-11", "retrieved_at": "2026-10-11T19:10:33Z", "content_hash": "d43f7def2bdadf8c303488d8b03f6500f3786ed227e6232872ca447906b69d98", "source_effective_date": "2021-03-22", "public_archive_url": null, "source_state": "current" }, "source": { "id": "maternal:action-i-anzctr", "source_type": "registry", "title": "The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial", "canonical_url": "https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000476336", "identifier_namespace": "anzctr", "identifier_value": "ACTRN12617000476336", "publication_date": null, "publisher": "Australian New Zealand Clinical Trials Registry", "edition": "Record as last updated 2021-03-22 (22/03/2021 on the page). Registered 2017-03-31 (31/03/2017) and marked as prospectively registered. Dates on the page are day/month/year.", "reuse_basis": "Short factual extraction. The page states that all rights are reserved and lists personal contact data, so its bytes were not saved. Public text is cite_only (fact-check decision of 2026-10-13): the page states all rights reserved, so public pages state the facts in the atlas's own words, with a citation and a link. Numbers and dates still bind through the quote table.", "public_text": "cite_only" } }, { "evidence_role": "opposes", "locator": "Main record fields", "applicability_note": "ICTRP mirror of CTRI gives the status as completed.", "snapshot": { "id": "maternal:ictrp-ctri-2017-04-008326-2026-10-11", "retrieved_at": "2026-10-11T19:10:34Z", "content_hash": "f80b7fcc0c2ca4a7ed56c92219e38fce42bacec3a4baef8335ed9806e6635485", "source_effective_date": "2021-11-24", "public_archive_url": null, "source_state": "unknown" }, "source": { "id": "maternal:action-i-ctri", "source_type": "registry", "title": "Improving newborn survival in preterm birth", "canonical_url": "http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=17527", "identifier_namespace": "ctri", "identifier_value": "CTRI/2017/04/008326", "publication_date": null, "publisher": "Clinical Trials Registry - India, read through the WHO ICTRP mirror", "edition": "WHO ICTRP mirror, refreshed 2021-11-24 (24 November 2021). Registered 2017-04-10, read as day-month-year because the CTRI number contains 2017/04; ICTRP marks it as prospectively registered. The primary CTRI record could not be read on 2026-10-11: the http request did not connect and the https request returned a short error page.", "reuse_basis": "Short factual extraction from the ICTRP mirror, not the primary register. The page lists personal contact data, so its bytes were not saved. Public text is cite_only (fact-check decision of 2026-10-13): the terms of the CTRI record, read through the WHO ICTRP mirror, are unverified, so public pages state the facts in the atlas's own words, with a citation and a link. Numbers and dates still bind through the quote table.", "public_text": "cite_only" } } ], "review": { "content_digest": "a4810ead2c689811edb08736324f0ef6152dfe1abd550568faff7e883bb0cd94", "current": [], "conflicting": [], "stale": [], "inactive": [] }, "api_path": "api/v1/claims/maternal--claim-action-i-stopped-early.json" } ], "decisions": [], "relationships": { "outgoing": [ { "predicate": "investigates", "label": "Tests dexamethasone given to the mother before preterm birth", "clinical_claim_not_fact": false, "other_entity_id": "maternal:antenatal-corticosteroids", "other_entity_in_atlas": true, "claim_id": null }, { "predicate": "investigates", "label": "Enrolled women at risk of imminent preterm birth", "clinical_claim_not_fact": false, "other_entity_id": "maternal:preterm-birth", "other_entity_in_atlas": true, "claim_id": null }, { "predicate": "investigates", "label": "Primary outcome: neonatal death by 28 completed days", "clinical_claim_not_fact": false, "other_entity_id": "maternal:outcome-neonatal-death-28d", "other_entity_in_atlas": true, "claim_id": null }, { "predicate": "sponsored_by", "label": "Trial sponsor (manuscript, ICTRP)", "clinical_claim_not_fact": false, "other_entity_id": "maternal:who", "other_entity_in_atlas": true, "claim_id": null }, { "predicate": "funded_by", "label": "Primary funder (manuscript, abstract)", "clinical_claim_not_fact": false, "other_entity_id": "maternal:gates-foundation", "other_entity_in_atlas": true, "claim_id": null }, { "predicate": "funded_by", "label": "Additional support (manuscript); credited as funder in the PubMed abstract", "clinical_claim_not_fact": false, "other_entity_id": "maternal:who", "other_entity_in_atlas": true, "claim_id": null }, { "predicate": "results_reported_in", "label": "Primary results, NEJM 2020", "clinical_claim_not_fact": false, "other_entity_id": "maternal:pub-action-i-nejm-2020", "other_entity_in_atlas": true, "claim_id": null } ], "incoming": [] }, "page_path": "studies/action-i-trial/", "context_path": "api/v1/context/maternal--action-i-trial.md" }