IDA is associated with poor neonatal outcomes and maternal morbidity. This clinical trial
will compare IV iron isomaltoside to IV iron sucrose for correction of IDA, along with
the potential impacts to the patient: physical, emotional and convenience. The study will
also take into consideration the financial and resource impacts to the healthcare system,
as well as determine the validity of using iron isomaltoside in second and third
trimester pregnancy.
The trial will be a randomized, comparative, single center, phase III trial with a 1:1
allocation ratio. There will be two groups involved in this trial. Group 1: A single dose
of IV iron isomaltoside. Group 2: Standard iron sucrose therapy.
Eligible participants will be screened for IDA during the initial appointment (greater or
equal to 13 weeks gestational age) with the obstetrical care provider.
Discussion/awareness about the study will be discussed at their appointment or over the
telephone with the obstetrical care provider. This information will only be discussed if
the patient requires IV iron repletion in second or third trimester pregnancy.
Enrollment inclusion/exclusion criteria must be met for the participant to receive the
information about the study.
Study personnel will discuss the clinical trial, including obtaining informed consent
with the eligible participant. Baseline vital signs and blood work will be documented
from the previous patient visit where IDA was diagnosed. Documentation and data
collection will occur at 3 other points within the clinical trial: Post iron infusion
(approximately 30 days after infusion), during delivery and at 6 weeks postpartum.
Standard community blood work requisitions will be used for blood work and blood tests
that occur within the community or health clinic setting. Standard Physician orders or
Pre Printed orders will be followed for tests, bloodwork and medication administration
while in hospital at the delivery admission. Participant duration will be from intake
(approximately 13 weeks gestation to 6 week follow up post delivery of infant). The
follow up at the 6 week appointment will be the end point for the participation of the
study. A total of approximately 231 days of involvement within the study duration for
each participant.
The study will be completed 36 months after the enrollment of the first participant or
when all patients have been recruited to satisfy the sample size calculation.
The sample size is calculated based on the primary endpoint (achievement of Hb≥110 g/L
after iron intervention). As iron isomaltoside has a faster rise in hgb (weeks 1 to 5)
with fewer visits, it is assumed that 5% of iron isomaltoside and 15% of iron sucrose
participants will have hgb <110 g/L at delivery. Given the 10% difference between groups
of patients achieving a hgb ≥110g/L in the iron isomaltoside group, it is calculated that
at a p of 0.05 and a power of 80%, 140 participants are required in each treatment group.
The primary endpoint of this trial is the correction of anemia, defined as Hgb greater or
equal to 110 g/L at trial post iron infusion (30 days post iron infusion (with measured
hemoglobin levels during delivery and at six weeks postpartum).
The secondary endpoint is the change in quality of life questionnaires from baseline,
post iron infusion, at delivery and 6 weeks postpartum through standard Redcap tools.
Additionally, any adverse event will be documented with appropriate follow up care.
Participant subjective data will also be collected based on tolerance of IV iron,
pregnancy related symptoms and quality of life comparing pre iron infusion, post iron
infusion, at delivery and again at 6 weeks post delivery. Participants will also be
required to answer questions related to convenience of appointment for iron infusion(s),
accessibility to the infusion appointments and post birth bonding with baby.
Analysis will be performed after data collection is complete using the latest version of
RStudio. Qualitative variables will be expressed as counts, percentages, quantitative
variables as mean +/- standard deviation or median (interquartile range [IQR] depending
on the variable distribution. Comparison of continuous variables will be performed using
the two sided Student's t test or Mann Whitney U test (where appropriate), and the chi
squared test or Fisher's exact test (where appropriate) to compare category variables.
The Kaplan Meier method will be used for the graphical assessment of time related events.
Analysis of the primary efficacy and safety endpoints will be by intention to treat.
Participants who withdraw either due to medical condition or expressed withdrawal will be
set as censored. No data relating to the withdrawal will be utilized in the data
analysis. The proportion of endpoints will be analyzed using logistic regression.
Continuous secondary endpoints will be analyzed by linear regression. For analyzing
missing data, model based multiple imputations will be used for both primary and
secondary outcomes.
Eligible pregnant women with iron deficiency will be recruited through the Department of
Obstetrics and Gynecology Department, or through health care providers that maintain
obstetrical care privileges at RGH.
Treatments arms will be allocated through a blocked randomization list prepared by an
online tool. Moreover, the randomization will be stratified by Hgb level in increments of
10g/L to pursue equal distribution of the two groups. The sequence list will not be
accessible to the investigators. Participants will be randomly assigned to receive either
IV iron isomaltoside or IV iron sucrose. IV iron sucrose is the comparator because it is
currently the formulation used for IDA during second and third trimester pregnancy in
Regina, Saskatchewan, Canada. Products will be stored as per the product monograph and as
per requirements and guidelines set out by the Saskatchewan Health Authority.
The Saskatchewan Health Authority will ensure that the written agreement to perform trial
related monitoring, audits, Research Ethics Board reviews and regulatory inspections, and
provide direct access to source data and/or documents of this clinical trial, as
required. Data and source documents must be readily available to the Research Ethics
Board, Health Canada, Therapeutic Products Directorate, inspectors, clinical trial team
members, including investigators and/or obstetrical care providers for the purposes of
compliance with regulatory requirements of the clinical protocol and purposes relating to
treatment, care and follow up of adverse drug reactions or by means of trace
back/lookback as required. Source data and documentation include patient records whether
hard copy or electronic, blood work, appointment dates and times, test and procedure
results relating to this clinical trial. All source documents must be accessible during
the clinical trial period and after the clinical trial has completed.