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Trial registered on ANZCTR


Registration number
ACTRN12619000283178p
Ethics application status
Submitted, not yet approved
Date submitted
21/01/2019
Date registered
25/02/2019
Date last updated
25/02/2019
Date data sharing statement initially provided
25/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The IRONWOMAN pilot feasibility study: oral versus intravenous iron therapy for iron deficiency anaemia in late pregnancy
Scientific title
The IRONWOMAN pilot feasibility study: a double blind randomised trial to compare feasibility of blinding of intravenous or oral iron replacement to placebo intravenous or oral therapy for iron deficiency anaemia in pregnancy
Secondary ID [1] 297057 0
Nil known
Universal Trial Number (UTN)
U1111-1227-1581
Trial acronym
IRONWOMAN
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Iron Deficiency Anaemia of Pregnancy 311057 0
Condition category
Condition code
Blood 309692 309692 0 0
Anaemia
Reproductive Health and Childbirth 309693 309693 0 0
Antenatal care
Reproductive Health and Childbirth 309694 309694 0 0
Fetal medicine and complications of pregnancy
Diet and Nutrition 309798 309798 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women will receive:
1) Intravenous ferric carboxymaltose (FCM) 1000mg on a single occasion following treatment allocation, and daily placebo capsules (composition not yet determined) from IV infusion to birth OR
2) Elemental oral iron capsules 80mg daily from IV infusion to birth and a placebo intravenous saline infusion on a single occasion following treatment allocation.
Both groups will begin capsules on the same day as the IV infusion, which will occur at a time suitable for the woman and the hospital.

Strategies to monitor adherence to the capsules include a participant medication diary, direct observation by study personnel of pill count at 4 weeks after the IV, and questions in follow-up surveys at 8 weeks post-infusion and 6 weeks post-partum.
Intervention code [1] 313331 0
Treatment: Drugs
Comparator / control treatment
As per standard of care for iron deficiency anaemia of pregnancy, both groups will receive an active treatment (either oral or intravenous iron, with matching placebo). As first-line oral treatment of iron-deficiency anaemia of pregnancy is current standard of care, oral iron (with intravenous placebo) is the control group in this study.
Control group
Active

Outcomes
Primary outcome [1] 318660 0
Proportion of women who correctly identify treatment allocation. This outcome will be assessed by study-specific questionnaire.
Timepoint [1] 318660 0
By 4 weeks after treatment commences. More specifically, women will be asked which treatment they think they received in study-specific questionnaires on the day of infusion and 4 weeks after the infusion.
Secondary outcome [1] 365605 0
Average level of patient acceptance of treatment for iron deficiency anaemia and being in the IRONWOMAN study using Likert scale on study specific questionnaires.
Timepoint [1] 365605 0
At baseline and 4 weeks after intravenous treatment
Secondary outcome [2] 365606 0
Average level of clinician acceptance of both IRONWOMAN study and patient's treatment for iron deficiency anaemia, using Likert scale on study specific questionnaires.
Timepoint [2] 365606 0
At baseline and 4 weeks after intravenous treatment
Secondary outcome [3] 365607 0
Change in Short Form-36 (SF-36) scores over time in intravenous versus oral iron group (assessed using the SF-36 questionnaire).
Timepoint [3] 365607 0
From baseline to 4 weeks post-intravenous infusion
Secondary outcome [4] 365608 0
Treatment adverse effects as per patient questionnaire (gastrointestinal symptoms including constipation, diarrhoea, nausea and vomiting, abdominal pain, flatulence, black stool, and general symptoms such as dizziness, rash and headache), including severity of symptoms if present (mild, moderate, severe). The questionnaire includes study-specific questions, as well as PROMIS questionnaires. More specifically, the PROMIS questionnaires used are the ones titled 'Gastrointestinal Nausea & Vomiting', 'Gastrointestinal Constipation' and 'Gastrointestinal DIarrhea'.
Timepoint [4] 365608 0
From baseline to 4 weeks after treatment commences (symptoms measured at baseline then 4 weeks after treatment commences, using the study-specific and PROMIS questions).
Secondary outcome [5] 365609 0
Treatment adherence oral medication, by group: pill count, proportion of women taking >90% of capsules, proportion of women taking >50% of capsules.
Timepoint [5] 365609 0
4 weeks after treatment commences and at time of birth (conclusion of treatment)
Secondary outcome [6] 365610 0
Proportion in each group with persistent iron-deficiency anaemia in late pregnancy (Hb<105g/dL). This will be assessed by haemoglobin and ferritin serum assays.
Timepoint [6] 365610 0
At 4 weeks after IV treatment and at birth admission
Secondary outcome [7] 365611 0
Proportion in each group receiving off-trial intravenous iron. This will be assessed using study-specific questionnaires at 4 weeks post-infusion, 8 weeks post-infusion and 6 weeks post-partum. Data linkage to medical records will also be used.
Timepoint [7] 365611 0
From study enrolment to postpartum hospital discharge and 6 weeks post partum
Secondary outcome [8] 365612 0
Number of eligible women approached who do not consent to the study
Timepoint [8] 365612 0
At study recruitment
Secondary outcome [9] 365613 0
Median Hb level in IV versus oral iron group. This will be assessed using haemoglobin serum assay.
Timepoint [9] 365613 0
4 weeks after treatment commences, and at birth
Secondary outcome [10] 365614 0
Other Maternal clinical outcomes IV versus oral iron group: Blood transfusion before birth or within birth admission or within 42 days postpartum. This will be assessed using data linkage to medical records and study-specific questionnaires.
Timepoint [10] 365614 0
From birth admission to 42 days postpartum
Secondary outcome [11] 365958 0
Other Maternal clinical outcomes IV versus oral iron group: Postpartum haemorrhage (PPH) >1000mL rates. This will be assessed using data linkage to medical records.
Timepoint [11] 365958 0
From birth admission to 42 days postpartum
Secondary outcome [12] 365959 0
Other Maternal clinical outcomes IV versus oral iron group: Estimated blood loss volume at birth (mL). This will be assessed using data linkage to medical records.
Timepoint [12] 365959 0
From birth admission to 42 days postpartum
Secondary outcome [13] 365960 0
Other Maternal clinical outcomes IV versus oral iron group: Rate of exclusive breastfeeding at hospital discharge. This will be assessed using a study-specific questionnaire at 6 weeks postpartum.
Timepoint [13] 365960 0
From birth admission to 42 days postpartum
Secondary outcome [14] 365961 0
Other Maternal clinical outcomes IV versus oral iron group: Mode of birth (vaginal, forceps or vacuum or caesarean section). This will be assessed using data linkage to medical records.
Timepoint [14] 365961 0
From birth admission to 42 days postpartum
Secondary outcome [15] 365962 0
Other Maternal clinical outcomes IV versus oral iron group: gestational diabetes. This will be assessed using data linakge to medical records.
Timepoint [15] 365962 0
From birth admission to 42 days postpartum
Secondary outcome [16] 365963 0
Other Maternal clinical outcomes IV versus oral iron group: Rates of antenatal admission . This will be assessed using data linkage to medical records.
Timepoint [16] 365963 0
From birth admission to 42 days postpartum
Secondary outcome [17] 365964 0
Other Maternal clinical outcomes IV versus oral iron group: Maternal high-dependency and/or intensive care admission. This will be assessed using data linkage to medical records.
Timepoint [17] 365964 0
From birth admission to 42 days postpartum
Secondary outcome [18] 365965 0
Other Maternal clinical outcomes IV versus oral iron group: Maternal length of stay postpartum. This will be assessed using data linkage to medical records.
Timepoint [18] 365965 0
From birth admission to 42 days postpartum
Secondary outcome [19] 365966 0
Other Maternal clinical outcomes IV versus oral iron group: Maternal readmission within 42 days of birth for childbirth related complications. This will be assessed using data linkage to medical records.
Timepoint [19] 365966 0
From birth admission to 42 days postpartum
Secondary outcome [20] 365967 0
Other Maternal clinical outcomes IV versus oral iron group: Maternal death. This will be assessed using data linkage to medical records.
Timepoint [20] 365967 0
From birth admission to 42 days postpartum
Secondary outcome [21] 365968 0
Other fetal/neonatal clinical outcomes: Rate of prematurity <37 completed weeks’ gestation. This will be assessed using data linkage to medical records.
Timepoint [21] 365968 0
From birth to 28 days of life
Secondary outcome [22] 365969 0
Other fetal/neonatal clinical outcomes: Rate of small-for-gestational age (<10th centile) for gestation and sex as per Australian birthweight centiles. This will be assessed using data linkage to medical records.
Timepoint [22] 365969 0
At birth
Secondary outcome [23] 365970 0
Other fetal/neonatal clinical outcomes: Birthweight. This will be assessed using data linkage to medical records.
Timepoint [23] 365970 0
At birth
Secondary outcome [24] 365978 0
Other fetal/neonatal clinical outcomes: Gestation at birth. This will be assessed using data linkage to medical records.
Timepoint [24] 365978 0
At birth
Secondary outcome [25] 365979 0
Other fetal/neonatal clinical outcomes: Admission to special care nursery and/or Neonatal Intensive Care. This will be assessed using data linkage to medical records.
Timepoint [25] 365979 0
From birth to 28 days of life
Secondary outcome [26] 365981 0
Other fetal/neonatal clinical outcomes: Perinatal death (stillbirth or neonatal death within 28 days of birth). This will be assessed using data linkage to medical records.
Timepoint [26] 365981 0
From birth to 28 days of life
Secondary outcome [27] 365982 0
Other fetal/neonatal clinical outcomes: Neonatal length of stay from birth to 28 days of life. This will be assessed using data linkage to medical records.
Timepoint [27] 365982 0
From birth to 28 days of life
Secondary outcome [28] 365983 0
Other fetal/neonatal clinical outcomes: Iatrogenic preterm birth (caesarean section or labour induction <37 weeeks+0 days gestation, excluding those that occur after spontaneous labour or rupture of membranes). This will be assessed using data linkage to medical records.
Timepoint [28] 365983 0
From birth to 28 days of life
Secondary outcome [29] 366089 0
Average level of patient acceptance of randomisation of treatment (Likert scale)
Timepoint [29] 366089 0
At baseline and 4 weeks after treatment
Secondary outcome [30] 366090 0
Average level of clinican acceptance of randomisation of treatment (Likert scale)
Timepoint [30] 366090 0
At baseline and 4 weeks of treatment
Secondary outcome [31] 366091 0
Change in Edinburgh Depression Scale (EDS) scores over time in intravenous versus oral iron group. Measured using EDS (validated questionnaire).
Timepoint [31] 366091 0
From baseline to 4 weeks post-intravenous infusion
Secondary outcome [32] 366092 0
Median ferritin level IV versus oral iron group. This will be assessed by serum assay.
Timepoint [32] 366092 0
4 weeks after treatment commences, and at birth
Secondary outcome [33] 366093 0
Change in MCV IV versus oral iron group. This will be assessed by serum assay.
Timepoint [33] 366093 0
4 weeks after treatment commences, and at birth
Secondary outcome [34] 366094 0
Other Maternal clinical outcomes IV versus oral iron group: preeclampsia. This will be assessed using data linkage to medical records.
Timepoint [34] 366094 0
From birth admission to 42 days postpartum
Secondary outcome [35] 366095 0
Other Maternal clinical outcomes IV versus oral iron group: antepartum haemorrhage. This will be assessed using data linakge to medical records.
Timepoint [35] 366095 0
From birth admission to 42 days postpartum.

Eligibility
Key inclusion criteria
Pregnant adult women (18 or more years of age) with singleton or twin pregnancy, and mild-moderate iron-deficiency anaemia of pregnancy (Haemoglobin 80-104 g/L and Ferritin <30µg/L) between 26 and 32+6 weeks’ gestation.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Age<18 years, higher-order multiple pregnancy, severe anaemia (haemoglobin <80g/L), anaemia without iron deficiency, known malabsorptive syndromes affecting the uptake of oral iron, contraindication/known hypersensitivity to either oral iron or intravenous iron, already received intravenous iron during this pregnancy or taking 80+mg/day of elemental iron for the last 2 weeks, active severe mental health condition or intellectual disability precluding informed consent, women with active bleeding, women who are likely to give birth in the next 6 weeks, blood transfusion this pregnancy, history of anaemia due to another cause e.g. thalassemia, hypersplenism or haemolytic anaemia or iron overload or disorders in iron utilisation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment through central randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation using randomisation programs
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
N/A
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculation: Given that by chance alone 50% of women will correctly identify treatment allocation (the primary outcome), sample size was calculated on, whether at 95% confidence level, proportion that guess treatment allocation is between 35% and 65%. Estimated required sample size for this parameter is 43, rounded up to 50 (25 women in each group).

Statistical analysis: Analysis will be by intention to treat. Data will initially be analysed descriptively and normality of distribution assessed. Categorical variables will be compared between groups using Chi-squared testing, and continuous variables using student’s t-test (or Mann-Whitney-U testing for non-normally distributed variables). P-value <0.05 will be considered significant for primary outcome assessment and the secondary outcome assessment of whether clinicians correctly identify treatment allocation, and p-value <0.01 will be considered significant for other secondary outcomes. Given the short timeframe of recruitment and small numbers of participants, there will be no interim analysis, and data analysis will be performed in full at study completion.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2019
Actual
Date of last participant enrolment
Anticipated
1/10/2019
Actual
Date of last data collection
Anticipated
14/01/2020
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 12872 0
Royal Hospital for Women - Randwick
Recruitment hospital [2] 12873 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 25347 0
2031 - Randwick
Recruitment postcode(s) [2] 25348 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 301627 0
Government body
Name [1] 301627 0
The National Blood Authority, Australia
Country [1] 301627 0
Australia
Primary sponsor type
Individual
Name
Dr Amanda Henry
Address
School of Women's and Children's Health
UNSW Medicine
Level 1, Royal Hospital for Women
Barker St, Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 301330 0
University
Name [1] 301330 0
University of New South Wales
Address [1] 301330 0
UNSW Sydney
NSW 2052
Country [1] 301330 0
Australia
Secondary sponsor category [2] 301331 0
Individual
Name [2] 301331 0
Dr Antonia Shand
Address [2] 301331 0
Department of Maternal-Fetal Medicine
Royal Hospital for Women
Barker St, Randwick NSW 2031
Country [2] 301331 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302352 0
South-Eastern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 302352 0
Ethics committee country [1] 302352 0
Australia
Date submitted for ethics approval [1] 302352 0
18/01/2019
Approval date [1] 302352 0
Ethics approval number [1] 302352 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89926 0
Dr Antonia Shand
Address 89926 0
Department of Maternal Fetal Medicine
Level 0,
Royal Hospital for Women
Barker Street
Randwick NSW 2031
Country 89926 0
Australia
Phone 89926 0
+61 414783472
Fax 89926 0
Email 89926 0
antonia.shand@sydney.edu.au
Contact person for public queries
Name 89927 0
Antonia Shand
Address 89927 0
Department of Maternal Fetal Medicine
Level 0,
Royal Hospital for Women
Barker Street
Randwick NSW 2031
Country 89927 0
Australia
Phone 89927 0
+61 414783472
Fax 89927 0
Email 89927 0
antonia.shand@sydney.edu.au
Contact person for scientific queries
Name 89928 0
Antonia Shand
Address 89928 0
Department of Maternal Fetal Medicine
Level 0,
Royal Hospital for Women
Barker Street
Randwick NSW 2031
Country 89928 0
Australia
Phone 89928 0
+61 414783472
Fax 89928 0
Email 89928 0
antonia.shand@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
From six months after publication of main trial findings, no end date
Available to whom?
Case-by-case basis at the discretion of the Primary Sponsor
Available for what types of analyses?
For IPD meta-analyses and case-by-case basis on request for other indications
How or where can data be obtained?
Access subject to approvals by Principal Investigator


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.