Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202105463874444 Date of Approval: 31/05/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The WHO ACTION (Antenatal CorticosTeroids for Improving Outcomes in Preterm Newborns) Trials
Official scientific title ACTION III: A multi-country, multi-centre, three-arm, parallel group, double-blind, placebo-controlled, randomized trial of two doses of antenatal corticosteroids for women with a high probability of birth in the late preterm period in hospitals in low-resource countries to improve newborn outcomes
Brief summary describing the background and objectives of the trial Rationale In summary, there is currently a lack of clarity on clinical benefits of ACS use in the late preterm period, and uncertainty about the potential for harm. While the ALPS trial suggests benefit for late preterm newborns, the generalizability of these reported benefits to low-resource settings is unclear. The possibility of additional benefit for mortality and morbidity reduction in settings with high mortality amongst preterm newborns has also not been explored. However, the ACT Trial raised concerns that the use of ACS at lower level facilities in LMICs may not confer benefit or could cause maternal and newborn harm. The safety and efficacy of ACS in low-resource facilities in the late preterm period is thus in equipoise, and an efficacy trial is needed. This is particularly urgent, given the high burden of preterm births, particularly late preterm birth in these settings. Preterm births are the single largest contributor to the high neonatal mortality seen in many LMICs. Also, recent studies indicate equipoise regarding the optimal regimen that could confer benefits while minimizing risks of harmful effects. WHO guidance on the use of ACS in preterm birth is currently restricted only to early preterm birth (< 34weeks of gestation). Further evidence on the efficacy and safety of ACS in late preterm birth is required before WHO recommendations on the use of ACS in late preterm period (>34 weeks to <37 weeks gestation) can be made. 1.2. Aims and Objectives The aim of this trial is to assess the benefits and possible harms of two regimens of antenatal corticosteroids, dexamethasone phosphate 4x6mg IM q12h and betamethasone phosphate 4x2mg IM q12h, compared to placebo, when given to pregnant women in the late preterm period (gestation age of 34+0 to 36+5 weeks) when they are at risk of preterm birth. The trial will be conducted in hospitals in low-resource countries, where the WHO ACS treatment criteria can be met.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ACTION Trial
Disease(s) or condition(s) being studied Obstetrics and Gynecology
Sub-Disease(s) or condition(s) being studied Late preterm birth
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/09/2021
Actual trial start date
Anticipated date of last follow up 30/08/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 2520
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Dexamethasone Phosphate 4x6mg q12h a total of 4 doses Corticosteroid 630
Experimental Group Betamethasone phosphate 4x2mg IM q12h a total of 4 doses Corticosteroid 630
Control Group Normal Saline 48 hours Placebo 1260 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Gestational age from 34 weeks 0 days to 36 weeks 5 days • High probability of late preterm birth (up to 36+6 weeks) defined as birth expected between 12 hours and 7 days after randomization as a result of: A. Membrane rupture without preterm labour (where preterm labour is defined as at least 6 regular uterine contractions/ hr and any one of the following: cervical dilatation of ≥ 3 cm or effacement ≥75%). OR B. Preterm labour with intact membranes, defined as at least 6 regular contractions/hr and one of the following: (i) cervix ≥3cm dilated or (ii) 75% effaced; OR C . Planned delivery by induction of labour or caesarean section between 24hours and 7 days, as deemed necessary by the provider. An induction must be scheduled to start by 36+5 weeks at the latest, whereas a caesarean delivery must be scheduled by 36+6 weeks at the latest • Singleton or multiple pregnancies, where the foetus/es (or at least one foetus in a multiple pregnancy) is/are confirmed alive by doppler or USG • Women with no clinical signs of severe infection (as per obstetric care physician’s assessment) • Women willing and able to provide consent (or if a minor, provides assent and guardian provides consent) Women with the following conditions will be eligible. Any comorbid conditions will be managed according to local guidelines, and in line with WHO recommendations: o Women with a history of previous preterm birth o Women with hypertensive disorders o Women with a growth impaired foetus o Women with pre-gestational or gestational diabetes o Women with HIV/AIDs • Ruptured membranes with cervix dilated ≥ 3cm or effaced ≥75%, or with more than 6 contractions per hour (or both) • Cervical dilation ≥ 8 cm with intact membranes • Clinical suspicion or evidence of clinical chorioamnionitis or severe infection, as per obstetric care physician assessment • Evidence of non-reassuring foetal status requiring immediate delivery • Major or lethal congenital foetal anomaly identified • No prior ultrasound-based estimate of gestational age available and immediate ultrasound examination is not possible • Any systemic corticosteroid use during the current pregnancy (outside of trial) • Unwilling or unable to provide consent or assent (including due to active labour) • Currently a participant in another clinical trial related to maternal and neonatal health, or previously participated in any ACTION trial • Any other clinical indication where the treating clinician considers corticosteroids to be contraindicated Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 16 Year(s) 49 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/02/2021 Kenyatta National Hospital University of Nairobi ERC
Ethics Committee Address
Street address City Postal code Country
Hospital road Nairobi 00202 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary outcome: Stillbirth (post randomization) OR neonatal death within 72 hours of birth OR use of respiratory support within 72 hours of birth or until discharge from hospital, whichever is earlier. Use of respiratory support consists of any one of the following: (i) use of mechanical ventilation (ii) continuous use of CPAP for 12 hours or more with an FiO2 ≥0.4 at any time (iii) continuous use of supplementary oxygen for 24 hours or more with an FiO2 ≥0.4 at any time 72hrs
Secondary Outcome Newborn: Efficacy outcomes: (i) Stillbirths (ii) Neonatal death within 72 hours, 7 days, 28 days of birth (iii) Resuscitation at birth i.e. use of positive pressure ventilation (iv) Severe respiratory distress (SRD) within 72 hours after birth or until discharge from hospital, whichever is earlier. SRD is defined as any of the following clinical signs: respiratory rate ≥70/ min, chest indrawing, grunting, or SpO2 less than 90%, any of which are present at two or more consecutive 6 hourly assessments. (v) Use of respiratory support i.e. any one of the following: (i) mechanical ventilation (ii) continuous use of CPAP for 12 hours or more with an FiO2 ≥0.4 at any time (iii) continuous use of supplementary oxygen for 24 hours or more with an FiO2 ≥0.4 at any time (vi) Still birth OR neonatal death in 72h OR mechanical ventilation OR need for very high CPAP settings (≥8 cm water pressure and ≥0.7 FiO2) in 72h after birth (vii) Cause specific mortality Safety outcomes: (i) Clinically suspected neonatal sepsis (≤7d) (ii) Neonatal hypoglycaemia (blood glucose < 45 mg% at 2, 6, 12, 24 or 36 h, or detected anytime < 36 h based on a test because of clinical suspicion) Health service utilization outcomes: (i) Admission to neonatal care unit (ii) Duration of hospitalization (iii) Any parenteral antibiotic use Maternal Safety outcomes: (i) Possible maternal bacterial infection during hospital admission: Occurrence of maternal fever, or clinically suspected or confirmed infection, for which therapeutic antibiotics were used (ii) Chorioamnionitis (iii) Post-partum endometritis (iv) Maternal death (from time of randomization to 28 completed days after birth) 72hrs 7 days 28 days
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Coast General Teaching and Referral Hospital Kisauni Road Mombasa 80100 Kenya
Thika Level 5 Hospital General Kago Road Thika 01000 Kenya
Nakuru level 5 hospital Show ground road Nakuru 20100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
World Health Organization Avenue Appia Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor World Health Organization Avenue Appia Geneva Switzerland Funding Agency
COLLABORATORS
Name Street address City Postal code Country
University of Nairobi Mbagathi road Nairobi 00202 Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Zahida Qureshi zahida@qureshi.co.ke +254721310750 Mbagathi road
City Postal code Country Position/Affiliation
Nairobi Kenya Associate Professor at The University of Nairobi
Role Name Email Phone Street address
Scientific Enquiries Fredrick Were frednwere@gmail.com +254722718770 Mbagathi road
City Postal code Country Position/Affiliation
Nairobi Kenya Professor at The University of Nairobi
Role Name Email Phone Street address
Public Enquiries John Kinuthia kinuthia@uw.edu +254722799052 Hospital road
City Postal code Country Position/Affiliation
Nairobi Kenya Head of Research and Programs at Kenyatta National Hospital
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes This project will generate an anonymised research dataset, with de-identified information of characteristics and outcomes from all women and newborns participating in the trial. Informed Consent Form,Study Protocol Within 12 months after study completion Once the trial is completed and primary results published, this dataset will be available for study partners to use for further analyses. Each site will have access to its own site data during the trial to facilitate self-monitoring by the site team To ensure confidentiality, data will be anonymised of any identifying participant or site information. WHO is responsible for ensuring the permanent storage of the trial data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information