ANZCTR - Registration

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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]

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

Condition category

Condition code

Blood

Anaemia

Reproductive Health and Childbirth

Antenatal care

Reproductive Health and Childbirth

Fetal medicine and complications of pregnancy

Diet and Nutrition

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]

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]

Proportion of women who correctly identify treatment allocation. This outcome will be assessed by study-specific questionnaire.

Timepoint [1]

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]

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]

At baseline and 4 weeks after intravenous treatment

Secondary outcome [2]

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]

At baseline and 4 weeks after intravenous treatment

Secondary outcome [3]

Change in Short Form-36 (SF-36) scores over time in intravenous versus oral iron group (assessed using the SF-36 questionnaire).

Timepoint [3]

From baseline to 4 weeks post-intravenous infusion

Secondary outcome [4]

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]

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]

Treatment adherence oral medication, by group: pill count, proportion of women taking >90% of capsules, proportion of women taking >50% of capsules.

Timepoint [5]

4 weeks after treatment commences and at time of birth (conclusion of treatment)

Secondary outcome [6]

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]

At 4 weeks after IV treatment and at birth admission

Secondary outcome [7]

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]

From study enrolment to postpartum hospital discharge and 6 weeks post partum

Secondary outcome [8]

Number of eligible women approached who do not consent to the study

Timepoint [8]

At study recruitment

Secondary outcome [9]

Median Hb level in IV versus oral iron group. This will be assessed using haemoglobin serum assay.

Timepoint [9]

4 weeks after treatment commences, and at birth

Secondary outcome [10]

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]

From birth admission to 42 days postpartum

Secondary outcome [11]

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]

From birth admission to 42 days postpartum

Secondary outcome [12]

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]

From birth admission to 42 days postpartum

Secondary outcome [13]

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]

From birth admission to 42 days postpartum

Secondary outcome [14]

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]

From birth admission to 42 days postpartum

Secondary outcome [15]

Other Maternal clinical outcomes IV versus oral iron group: gestational diabetes. This will be assessed using data linakge to medical records.

Timepoint [15]

From birth admission to 42 days postpartum

Secondary outcome [16]

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]

From birth admission to 42 days postpartum

Secondary outcome [17]

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]

From birth admission to 42 days postpartum

Secondary outcome [18]

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]

From birth admission to 42 days postpartum

Secondary outcome [19]

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]

From birth admission to 42 days postpartum

Secondary outcome [20]

Other Maternal clinical outcomes IV versus oral iron group: Maternal death. This will be assessed using data linkage to medical records.

Timepoint [20]

From birth admission to 42 days postpartum

Secondary outcome [21]

Other fetal/neonatal clinical outcomes: Rate of prematurity <37 completed weeks’ gestation. This will be assessed using data linkage to medical records.

Timepoint [21]

From birth to 28 days of life

Secondary outcome [22]

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]

At birth

Secondary outcome [23]

Other fetal/neonatal clinical outcomes: Birthweight. This will be assessed using data linkage to medical records.

Timepoint [23]

At birth

Secondary outcome [24]

Other fetal/neonatal clinical outcomes: Gestation at birth. This will be assessed using data linkage to medical records.

Timepoint [24]

At birth

Secondary outcome [25]

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]

From birth to 28 days of life

Secondary outcome [26]

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]

From birth to 28 days of life

Secondary outcome [27]

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]

From birth to 28 days of life

Secondary outcome [28]

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]

From birth to 28 days of life

Secondary outcome [29]

Average level of patient acceptance of randomisation of treatment (Likert scale)

Timepoint [29]

At baseline and 4 weeks after treatment

Secondary outcome [30]

Average level of clinican acceptance of randomisation of treatment (Likert scale)

Timepoint [30]

At baseline and 4 weeks of treatment

Secondary outcome [31]

Change in Edinburgh Depression Scale (EDS) scores over time in intravenous versus oral iron group. Measured using EDS (validated questionnaire).

Timepoint [31]

From baseline to 4 weeks post-intravenous infusion

Secondary outcome [32]

Median ferritin level IV versus oral iron group. This will be assessed by serum assay.

Timepoint [32]

4 weeks after treatment commences, and at birth

Secondary outcome [33]

Change in MCV IV versus oral iron group. This will be assessed by serum assay.

Timepoint [33]

4 weeks after treatment commences, and at birth

Secondary outcome [34]

Other Maternal clinical outcomes IV versus oral iron group: preeclampsia. This will be assessed using data linkage to medical records.

Timepoint [34]

From birth admission to 42 days postpartum

Secondary outcome [35]

Other Maternal clinical outcomes IV versus oral iron group: antepartum haemorrhage. This will be assessed using data linakge to medical records.

Timepoint [35]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Hospital for Women - Randwick

Recruitment hospital [2]

St George Hospital - Kogarah

Recruitment postcode(s) [1]

2031 - Randwick

Recruitment postcode(s) [2]

2217 - Kogarah

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

The National Blood Authority, Australia

Address [1]

Level 2, 243 Northbourne Avenue, Lyneham Australian Capital Territory 2602

Country [1]

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]

University

Name [1]

University of New South Wales

Address [1]

UNSW Sydney
NSW 2052

Country [1]

Australia

Secondary sponsor category [2]

Individual

Name [2]

Dr Antonia Shand

Address [2]

Department of Maternal-Fetal Medicine
Royal Hospital for Women
Barker St, Randwick NSW 2031

Country [2]

Australia

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

South-Eastern Sydney Local Health District Human Research Ethics Committee

Ethics committee address [1]

Prince of Wales Hospital
G71 East Wing
Edmund Blacket Building
RANDWICK NSW 2031

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/01/2019

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Iron-deficiency anaemia (IDA) affects approximately 1 in 7 Australian pregnant women, and optimal treatment for improving maternal wellbeing and decreasing blood transfusion remains uncertain. An issue with prior randomised trials of IV versus oral iron is lack of patient and clinician blinding to treatment received, so the primary aim of this study is therefore to determine the feasibility and effectiveness of blinding treatment allocation to IV iron or saline placebo infusion. Participants will be pregnant women with iron deficiency anaemia between 26 weeks and 33 weeks gestation, and will either be given IV iron and placebo capsules or iron capsules and placebo IV. It is expected that using an opaque sleeve covering the syringe and giving set when administering IV iron or saline placebo, followed by matching placebo or active iron oral tablets, respectively, is feasible and effective.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Antonia Shand

Address

Department of Maternal Fetal Medicine
Level 0,
Royal Hospital for Women
Barker Street
Randwick NSW 2031

Country

Australia

Phone

+61 414783472

Fax

[email protected]

Contact person for public queries

Name

Dr Antonia Shand

Address

Department of Maternal Fetal Medicine
Level 0,
Royal Hospital for Women
Barker Street
Randwick NSW 2031

Country

Australia

Phone

+61 414783472

Fax

[email protected]

Contact person for scientific queries

Name

Dr Antonia Shand

Address

Department of Maternal Fetal Medicine
Level 0,
Royal Hospital for Women
Barker Street
Randwick NSW 2031

Country

Australia

Phone

+61 414783472

Fax

[email protected]

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?

Current supporting documents:

Updated to:

Doc. No.	Type	Email
23714	Clinical study report	[email protected]
23715	Study protocol	[email protected]
23716	Informed consent form	[email protected]
23717	Ethical approval	[email protected]

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.

Trial Review

Documents added manually

Documents added automatically