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Trial registered on ANZCTR


Registration number
ACTRN12615000950561
Ethics application status
Approved
Date submitted
1/06/2014
Date registered
10/09/2015
Date last updated
14/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to assess whether two different doses of antenatal intravenous iron administration (500 mg and 1000mg ferric carboxymaltose) are equivalent in replenishing and sustaining iron stores successfully in pregnant iron deficient women
Scientific title
A study to assess whether two different doses of antenatal intravenous iron administration (500 mg and 1000mg ferric carboxymaltose) are equivalent in replenishing and sustaining iron stores successfully in pregnant iron deficient women
Secondary ID [1] 284670 0
none
Universal Trial Number (UTN)
U1111-1157-5881
Trial acronym
PROTECTIVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Iron deficiency 292062 0
post partum depression 292063 0
Condition category
Condition code
Blood 292401 292401 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
initially single dose of intravenous ferric carboxymaltose 500mg in 2nd or 3rd trimester
Intervention code [1] 289496 0
Treatment: Drugs
Comparator / control treatment
initially single dose of intravenous ferric carboxymaltose 1000mg in 2nd or 3rd trimester
Control group
Dose comparison

Outcomes
Primary outcome [1] 292262 0
% of patients requiring additional doses to maintain serum ferritin > 30mcg/L, and transferrin saturation < 25% or a ferritin < 50mcg/L, and transferrin saturation < 20% in women with an elevated CRP,
Maximal follow up is 12 months post partum
Timepoint [1] 292262 0
at 4-6 weeks after infusion,
at delivery,
6 weeks, 3, 6, 12 months post-partum or at the time of next pregnancy, if this occurs prior to the 12 month timepoint.
Secondary outcome [1] 308585 0
Evolution (Total iron requirements) of other iron/haematological parameters (serum ferritin, transferrin saturation, serum iron, soluble serum transferrin receptor)
Timepoint [1] 308585 0
at baseline,3, 6, 12 months post-partum



Secondary outcome [2] 313612 0
neonatal iron status of cord blood
Timepoint [2] 313612 0
at delivery
Secondary outcome [3] 315231 0
changes post treatment in
- Mental health assessment in association with iron status (prim endpoint);
- Assessments of psychiatric diagnoses (MINI), depression and anxiety symptoms (SIGH-AD, EDPS),
- and general functioning (ANRQ, GAF)
Timepoint [3] 315231 0
6 weeks post partum
12 months post partum
Secondary outcome [4] 344422 0
Gestational age at delivery, Information from antenatal record and case notes entry at delivery
Timepoint [4] 344422 0
Antenatal period and at delivery
Secondary outcome [5] 344423 0
Neonatal outcomes including:
Birth weight and Customized birth weight centile, composite outcome, assessed from birth record after birth
Timepoint [5] 344423 0
At birth , assessed from birth record
Secondary outcome [6] 344424 0
Infant developmental status (Ages and Stages ASQ3 - 12 Month Questionnaire)
Timepoint [6] 344424 0
12 months follow up.
Secondary outcome [7] 344425 0
Preterm delivery
defined as delivery less than 37 weeks gestation
assessed from medical records
Timepoint [7] 344425 0
preterm labour
defined as regular contractions of the uterus resulting in changes in the cervix that start before 37 weeks of pregnancy, assessed at time of delivery
Secondary outcome [8] 344426 0
PPROM
amniotic sac or “water” breaks prior to 37 weeks
assessed from medical records
Timepoint [8] 344426 0
time when it occurs, at time of delivery
Secondary outcome [9] 344427 0
Gestational diabetes, assessed from medical records
Timepoint [9] 344427 0
during pregnancy, assessed at medical follow ups at week 28 and week 36 of pregnancy, or at any other unscheduled follow ups
Secondary outcome [10] 344428 0
Pregnancy Hypertension (chronic hypertension, gestational hypertension, pre-eclampsia (de novo or superimposed, white coat hypertension), assessed from medical records
Timepoint [10] 344428 0
after 20 weeks of pregnancy, assessed at time of delivery
Secondary outcome [11] 344429 0
Pre-eclampsia – according to ISSHP (2014) definition (hypertension developing after 20 weeks gestation and the co-existence of one or more of: proteinuria, maternal organ dysfunction or uteroplacental dysfunction/fetal growth restriction, assessed from medical records
Timepoint [11] 344429 0
after 20 weeks gestation
assessed at time of delivery
Secondary outcome [12] 344430 0
Mode of delivery – vaginal, instrumental, caesarean section (elective, emergency both for non-progressive labour and suspected fetal distress).
assessed from hospital record after delivery
Timepoint [12] 344430 0
at delivery, assessed from hospital record
Secondary outcome [13] 344431 0
Antepartum haemorrhage,
defined as bleeding from or in to the genital tract, occurring from 24+0 weeks of pregnancy and prior to the birth of the baby
assessed from medical records
Timepoint [13] 344431 0
from 24 weeks of pregnancy
at delivery, assessed from medical record
Secondary outcome [14] 344432 0
Postpartum haemorrhage,
when there is loss of more than 500 mL after a vaginal birth or 1000 mL following a caesarean section, in the first 24 hours.
assessed from medical records
Timepoint [14] 344432 0
after delivery within the first 24 hours following childbirth.
assessed from medical records
Secondary outcome [15] 344433 0
fetal death, defined as spontaneous intrauterine death of a fetus at any time during pregnancy.
assessed from medical records
Timepoint [15] 344433 0
at any time during pregnancy., data collected throughout pregnancy
assessed from medical records
Secondary outcome [16] 344434 0
Birth length,data taken from midwife entry, assessed from medical record
Timepoint [16] 344434 0
at birth
Secondary outcome [17] 344435 0
Head circumference, data taken from midwife entry, assessed from medical record
Timepoint [17] 344435 0
at birth
Secondary outcome [18] 344436 0
Neonatal resuscitation, data taken from case note entry, assessed from medical record
Timepoint [18] 344436 0
after delivery, immediately after birth, assessed from medical records
Secondary outcome [19] 344437 0
Oxygen therapy (>4 hours)
assessed from medical records
Timepoint [19] 344437 0
after delivery
retrospective review from case note records

Eligibility
Key inclusion criteria
Pregnant women (2nd and 3rd trimester) with iron deficiency (serum ferritin <15mcg/mL transferrin saturation < 25%; if elevated CRP then serum ferritin <50mcg/mL and TSAT <20%).
Minimum age
18 Years
Maximum age
50 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Patients with B12 pmol/L or folate nmol/L deficiency that cannot be corrected before trial entry will be excluded.
2.Known hypersensitivity to ferric carboxymaltose or not eligible for dosing per approved Product Insert
3.Haemoglobin (Hb) >130g/dL
4.Hemochromatosis or other iron storage disorders
5.Serious medical condition, uncontrolled systemic disease or any other medical condition (including an inability to fully comprehend and/or perform study procedures) that, in the judgment of the Investigator, prohibits the patient from entering or potentially completing the study

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 by telephone randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated random number sequence
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We expect 20% of patients in each arm of the study to require a top up iron infusion, regardless of whether they are in the 1000mg or 500mg arm.
A difference greater than 5% would indicate that one was better than the other (ie if one had rates either less than 15% or greater than 25%) it would be better/worse than the other dose. If these assumptions are correct, then we need 128 in each arm as a baseline. If we then expect 15% drop out, we would need 150 in each arm of the study

Data will be analysed using a range of computerised statistical methods. Specific analyses will depend upon the data. The primary outcome (requirement for additional iron infusion) will be compared between the two groups using Chi Squared analysis. The blood test data will be compared using t-tests and repeated measures ANOVA for analysis of time effects within participants. The mental health data will be analysed using t-tests, analysis of variance, correlational analysis, regression, chi-square, validity and reliability checks on Cronbach’s alpha, and principal components analysis where appropriate. Non-parametric tests will be undertaken if data sets are not suitable for parametric analysis.
To ensure both safety data and efficacy data an interim analysis is going to be performed once 50% of the calculated sample size is reached (or in the event that greater than expected adverse outcomes are observed). This will be assessed by an independent third party, including a statistician and an expert in the field. This will involve interpretation of the analysis, in order to determine if it is imperative to act and initiate a data-dependent stopping of the trial. This can be done based on the following two aspects:
*Treatments are found to be convincingly different by impartial knowledgeably experts
*Side effects or toxicity are too severe to continue treatment in light of potential benefits

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2526 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 8211 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 289327 0
Hospital
Name [1] 289327 0
Lyell McEwin Hopsital
Address [1] 289327 0
Haydown Rd
Elizabeth Vale SA 5112
Country [1] 289327 0
Australia
Funding source category [2] 298984 0
Government body
Name [2] 298984 0
National Blood Authority
Address [2] 298984 0
Level 2/243 Northbourne Ave, Lyneham ACT 2602
Country [2] 298984 0
Australia
Primary sponsor type
Hospital
Name
Lyell McEwin Hospital
Address
Haydown Rd
Elizabeth Vale SA 5112
Country
Australia
Secondary sponsor category [1] 289621 0
None
Name [1] 289621 0
Address [1] 289621 0
Country [1] 289621 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291093 0
TQEH HREC
Ethics committee address [1] 291093 0
The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South SA 5011
Ethics committee country [1] 291093 0
Australia
Date submitted for ethics approval [1] 291093 0
Approval date [1] 291093 0
04/02/2015
Ethics approval number [1] 291093 0
HREC/14/TQEHLMH/122

Summary
Brief summary
The aim of this study is to assess whether two different doses of antenatal intravenous iron administration (500 mg and 1000mg ferric carboxymaltose) are equivalent in replenishing and sustaining iron stores successfully in pregnant iron deficient women.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48706 0
A/Prof Bernd Froessler
Address 48706 0
Lyell McEwin Hospital
Dept of Anaesthesia
Haydown Rd
Elizabeth Vale
SA 5112
Country 48706 0
Australia
Phone 48706 0
+61881829000
Fax 48706 0
Email 48706 0
bernd.froessler@health.sa.gov.au
Contact person for public queries
Name 48707 0
A/Prof Bernd Froessler
Address 48707 0
Lyell McEwin Hospital
Dept of Anaesthesia
Haydown Rd
Elizabeth Vale
SA 5112
Country 48707 0
Australia
Phone 48707 0
+61881829000
Fax 48707 0
Email 48707 0
bernd.froessler@health.sa.gov.au
Contact person for scientific queries
Name 48708 0
A/Prof Bernd Froessler
Address 48708 0
Lyell McEwin Hospital
Dept of Anaesthesia
Haydown Rd
Elizabeth Vale
SA 5112
Country 48708 0
Australia
Phone 48708 0
+61881829000
Fax 48708 0
Email 48708 0
bernd.froessler@health.sa.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary