Treatment of iron deficiency anaemia in pregnancy study

ISRCTN	ISRCTN13007439
DOI	https://doi.org/10.1186/ISRCTN13007439
ClinicalTrials.gov (NCT)	NCT03725150
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	2018OBS100
Sponsor	The Royal Wolverhampton NHS Trust,
Funder	Rotha Abraham Trust

Submission date: 20/02/2019
Registration date: 25/06/2019
Last edited: 12/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Over a third of pregnant women are anaemic by their third trimester of pregnancy. The most common cause is iron deficiency (low iron in the blood). The main reason is rising iron requirements throughout pregnancy. Anaemia can make pregnant women feel tired and unwell. There is some evidence that anaemia may also increases the risk of babies being born prematurely and/or underweight. The evidence shows that anaemia could also be a risk factor for stillbirth and neonatal death. It can also be a real problem around the time of delivery if a mother bleeds when she is already anaemic. This increases the chance of her anaemia carrying on after pregnancy leading to more risk of infections and problems with breast feeding. Also, in more severe cases there will be more need for a blood transfusion.

Although we know how to treat this type of anaemia we don’t know how effective the treatment is, or how severe the side effects are for pregnant women. In fact, we know that many pregnant women are troubled by these side effects and thus don’t take the iron in the recommended way. This study aims to better understand anaemia and how to use oral iron therapy for iron deficiency anaemia in pregnant women. This includes recording the effect of treatment on anaemia symptoms, side effects, and the level of success of iron therapy using several blood tests.

Who can participate?
Anaemic pregnant women and those anaemic up to 6 weeks postpartum are invited to participate in this study and treated using an iron treatment schedule as described in national guidelines.

What does the study involve?
Blood samples for routine care and research will be taken at each clinic visit and tested to better understand iron metabolism and to better predict the response to oral iron therapy during pregnancy. Women will be asked to complete three short questionnaires at each visit and complete a symptoms diary for 2-4 weeks whilst taking iron tablets.

What are the possible benefits and risks of participating?
There is no risk to women and their fetus in taking part in this study as we are following routine standard care and treatment of anaemia. There may be some inconvenience in completing the study diary and questionnaires. Some women might suffer side effects from the iron tablets, but they will be closely monitored by the research doctor who will give further advice on what to do.

Where is the study run from?
This study is run from the Royal Wolverhampton NHS Trust .

When is the study starting and how long is it expected to run for?
June 2018 to March 2020

Who is funding the study?
Rotha Abraham Trust

Who is the main contact?
Mr David Churchill
david.churchill1@nhs.net

Prof Simon Stanworth
simon.stanworth@nhsbt.nhs.uk

Contact information

Mr David Churchill
Scientific

The Royal Wolverhampton NHS Trust, New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom

ORCID ID	0000-0003-0548-2953
Phone	01902 695153
Email	david.churchill1@nhs.net

Prof Simon Stanworth
Scientific

Department of Haematology
Consultant Haematologist
Oxford University Hospitals NHS Foundation Trust/NHSBT
Level 2, John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9BQ
United Kingdom

ORCID ID	0000-0002-7414-4950
Phone	+44 (0)1865
Email	simon.stanworth@nhsbt.nhs.uk

Study information

Primary study design	Observational
Study design	Prospective cohort study.
Secondary study design	Cohort study
Participant information sheet	ISRCTN13007439_PIS_V1.2_24May2018.pdf
Scientific title	Iron deficiency anaemia in pregnancy: an observational study of tolerability, compliance with oral iron therapy and effects on haematological/biochemical markers
Study acronym	TIAP
Study objectives	To better define the natural history and understand how to use oral iron therapy for iron deficiency anaemia in pregnant women. Specifically, the study will document the impact of treatment on symptomatology, the induction of side effects, and the utility of several haematological indices; haemoglobin, ferritin, transferrin saturation, reticulocyte haemoglobin concentration, alongside changes in new markers of iron homeostasis (hepcidin), which may better predict the success of treatment with iron.
Ethics approval(s)	Approved 23/04/2018, the West Midlands - Black Country Research Ethics Committee (West Midlands - Black Country Research Ethics Committee, The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS; 0207 1048106, 0207 104 8102; nrescommittee.westmidlands-blackcountry@nhs.net), ref: 18/WM/0090.
Health condition(s) or problem(s) studied	Iron deficiency anaemia in pregnancy
Intervention	This study is an observational study of practice. Anaemic pregnant women will be invited to participate in a study aiming to assess response and tolerability to current doses and schedules for oral iron, as recommended in national (BSH) guidelines. At follow-up clinic visits a full blood count will be performed as per standard care. The following assessment/tests will also be performed as part of this study: 1. Blood samples will be taken for subsequent detailed analysis of pathways of iron metabolism. 2. Participants will be asked to complete Quality of Life questionnaires (The World Health Organisation- Five Well-Being Index (WHO-5), and the Well-being in Pregnancy (WiP) questionnaire.) 3. An additional Questionnaire to investigate the barriers and enablers to taking oral iron therapy 4. Participants will be asked to complete a tolerability and symptom diary Pregnancy and fetal outcome data will also be collected 8 weeks after birth. These data are collected routinely for this group of women.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Ferrous sulphate
Primary outcome measure(s)	The proportion of pregnant women who meet the criteria for a clinical response, defined as an increase in haemoglobin concentration of 10g/l measured using serum haemoglobin concentration at baseline and 2-4 weeks after the onset of iron therapy.
Key secondary outcome measure(s)	1. The change in frequency and severity of symptoms associated with anaemia in pregnancy measured using The ‘Anaemia in Pregnancy Assessment Questionnaire’ at baseline and any subsequent visit/s (depending on how many visits required but a minimum of one visit measurement is required at 2-4 weeks after the onset of iron therapy). 2. The frequency and severity of side effects induced by iron therapy to treat anaemia measured using tolerability and symptom diary at baseline and any subsequent visit/s (depending on how many visits required but a minimum of one visit measurement is required at 2-4 weeks after the onset of iron therapy). 3. A measurement of compliance with currently recommended oral iron regimens prescribed in pregnancy measured using tolerability and symptom diary and the need for dose adjustments in line with BSCH guidelines at baseline and any subsequent visit/s (depending on how many visits required but a minimum of one visit measurement is required at 2-4 weeks after the onset of iron therapy) 4. To document the longitudinal changes in haemoglobin, red cell indices, iron, transferrin, ferritin, CRP, during a treatment course of oral iron measured using serum haemoglobin, red cell indices, iron, transferrin, ferritin, CRP concentration at baseline and any subsequent visit/s (depending on how many visits required but a minimum of one visit measurement is required at 2-4 weeks after the onset of iron therapy). 5. To investigate the changes in research biomarker serum hepcidin, and whether it can predict the response to oral iron measured by serum hepcidin at baseline and any subsequent visit/s (depending on how many visits required but a minimum of one visit measurement is required at 2-4 weeks after the onset of iron therapy).
Completion date	01/03/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	45 Years
Sex	Female
Target sample size at registration	120
Total final enrolment	111
Key inclusion criteria	1. Pregnant women (any stage during pregnancy up to 36 weeks) and women in the puerperium (within 6 weeks post-delivery) 2. Anaemia as defined by WHO criteria and described in British Society Haematology (BSH)/ British Committee for standards in Haematology (BCSH) guidelines. 2.1. First trimester < 110g/l 2.2. Second and third trimester < 105g/l 2.3. Puerperium < 100g/l 3. Age: 18-45 years
Key exclusion criteria	1. Presenting at or after 36 weeks 2. Affected by a (major) haemoglobinopathy e.g. B thalassaemia major sickle cell disease 3. Overt clinical signs of sepsis 4. Allergies to iron 5. Hyperemesis Gravidarum / persistent vomiting 6. Inflammatory conditions such as Crohns, ulcerative colitis, Systemic lupus erythematosus, Rheumatoid arthritis. 7. Chronic renal failure
Date of first enrolment	01/06/2018
Date of final enrolment	01/12/2019

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Royal Wolverhampton Hospitals NHS Trust

New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Mr David Churchill (david.churchill1@nhs.net) once the study write up and publications have been completed. The data will become available in 2021 once all the analyses and publications have been completed. It will be available for individual patient systematic reviews. Consent was not obtained from the participants who would need to be contacted by those wishing to utilise the data. These data are anonymised.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	version V1.2	24/05/2018	25/06/2019	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version 1.2	04/05/2018	25/10/2022	No	No

Additional files

ISRCTN13007439_PIS_V1.2_24May2018.pdf: Uploaded 25/06/2019
ISRCTN13007439_PROTOCOL_V1.2_04May18.pdf: Protocol file

Editorial Notes

12/09/2023: The intention to publish date was changed from 01/03/2023 to 31/10/2023.
25/10/2022: Protocol uploaded (not peer reviewed).
08/03/2022: The intention to publish date was changed from 01/03/2022 to 01/03/2023.
3. The plain English summary was updated to reflect these changes.
10/06/2021: The following changes have been made:
1. The overall trial end date has been changed from 01/06/2020 to 01/03/2020 and the plain English summary has been updated to reflect this change.
2. The intention to publish date has been changed from 01/12/2020 to 01/03/2022.
09/07/2020: IPD sharing statement added.
10/01/2020: The total final enrolment was added.
27/08/2019: Internal review.
25/06/2019: The participant information sheet has been uploaded.
08/04/2019: Trial's existence confirmed by the West Midlands - Black Country Research Ethics Committee.