Treatment of Nigerian women with Iron by drip or iron tablets taken by mouth, for low blood level, hours after delivery
| ISRCTN | ISRCTN51426226 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN51426226 |
| EudraCT/CTIS number | 2021-002867-23 |
| Secondary identifying numbers | 01/2.0 |
- Submission date
- 22/09/2022
- Registration date
- 03/10/2022
- Last edited
- 04/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
Iron deficiency anaemia is a condition where a lack of iron in the body leads to fewer red blood cells. Anaemia is a public health burden with a high incidence in Africa. Iron deficiency anaemia is often treated with high-dose iron tablets taken by mouth if it is mild or moderate in severity, while blood transfusion is give in severe cases of anaemia. Some women do not tolerate the tablets well as they may develop side effects like constipation, stomach pain, nausea or vomiting. Others forget to use the oral iron tablets and hence the blood levels still remain low. There are iron preparations in existence that can be given in infusion (drip) form and have been found to be safe, and their use for the treatment of iron deficiency anaemia after delivery is currently being studied. The aim of this study is to compare the effectiveness of ferric carboxymaltose (FCM) given as an infusion through a vein and oral ferrous sulphate (FS) taken by mouth for treating iron-deficiency anaemia in women after delivery, and to compare the acceptability of these two forms of iron preparation in Nigerian women with moderate or severe iron deficiency anaemia after delivery.
Who can participate?
Women aged between 15 and 49 who are anaemic (haemoglobin concentration <10 g/dL), and within 6-48 hours of delivery.
What does the study involve?
Information will be collected about the participants' health and delivery, after which blood samples will be taken for some tests which include iron studies, serum phosphate, and complete blood count. Participants will be randomly allocated to one of two drug treatment arms (FCM or FS group). Women in the FCM arm will be given ferric carboxymaltose in 200 ml of normal saline infusion (drip) and this will be given through the woman's vein over 20 minutes. Women in the FS arm will be started on ferrous sulphate tablets which will be given as one 200 mg tablet (containing 65 mg of elemental iron) twice a day until 6 weeks after delivery. They will be checked on the postnatal wards until discharge from hospital, and then followed up at the hospital or home at 2 weeks, 6 weeks, 3 months, and 6 months after delivery. During the follow-ups, questions about her health and that of their newborn will be asked, vital signs will be checked, specimens will be collected for investigation, and they will be assessed for depression, fatigue, maternal-to-infant bonding and quality of life at various intervals.
What are the possible benefits and risks of participating?
The study drugs to be used have been found to be safe in women after delivery and while breastfeeding. They may reduce the need for blood transfusion in women with low blood levels. Although, it is still possible to suffer some side effects from any of the medications like nausea, vomiting, and diarrhoea to any of the two study drugs. Participants will be monitored closely to identify any side effects and will be treated at no cost. All the study drugs will be given free of charge and all the tests relating to this research will also be done for free. Participants will be given contacts of their caregivers and will be sent regular reminders about their appointments. The findings of this study will improve the knowledge about the treatment of anaemia in women after delivery. This is planned to lead to the possible change of existing treatments, with improvement in the well-being of women after delivery and their newborns.
Where is the study run from?
University of Lagos (Nigeria)
When is the study starting and how long is it expected to run for?
February 2022 to December 2024
Who is funding the study?
Bill and Melinda Gates Foundation (USA)
Who is the main contact?
Prof. Bosede B. Afolabi, bbafolabi@unilag.edu.ng
Contact information
Scientific
Department of Obstetrics and Gynecology
Faculty of Clinical Sciences
College of Medicine
University of Lagos/Lagos University Teaching Hospital (LUTH)
P. M. B. 12003
Surulere.
Lagos
100254
Nigeria
 ORCID ID |
0000-0002-7511-7567 |
|---|---|
| Phone | +234 (0)8023154064 |
| bbafolabi@unilag.edu.ng |
Public
Department of Obstetrics and Gynecology
Lagos University Teaching Hospital (LUTH)
P. M. B. 12003
Surulere
Lagos
100254
Nigeria
| ORCID ID |
0000-0002-8522-3232 |
|---|---|
| Phone | +234 (0)8060416764 |
| wunmiadaramoye@gmail.com |
Study information
| Study design | Multicenter interventional parallel open-label individually randomized controlled trial with an implementation study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | 42481 PIS v1.1.pdf |
| Scientific title | Intravenous ferric carboxymaltose versus oral ferrous sulphate for the treatment of moderate to severe postpartum anaemia in Nigerian women |
| Study acronym | IVON-PP |
| Study hypothesis | Hypothesis 1: Intravenous ferric carboxymaltose is effective, tolerable and safe in treating iron deficiency anaemia in postpartum women compared with oral ferrous sulphate. Hypothesis 2: Intravenous ferric carboxymaltose is acceptable and feasible for use in treating postpartum iron deficiency anaemia in Nigeria compared with oral ferrous sulphate. |
| Ethics approval(s) | 1. Approved 01/03/2022, Lagos University Teaching Hospital Health Research and Ethics Committee (Room 107, 1st Floor, LUTH administrative block, Surulere, Lagos, Nigeria; +234 (0)15850737, +234 (0)15852187, +234(0)15852209, +234(0) 15852158, +234(0)15852111; luthethics@yahoo.com), ref: ADM/DCST/HREC/APP/4908 2. Approved 07/09/2022, National Health Research and Ethics Committee (11th Floor, Federal Secretariat Complex Phase III, Amadu Bello Way, Abuja, Nigeria; +234 (0)9 523-8367;chairman@nhrec.net), ref: NHREC/01/01/2007 3. Approved 08/09/2022, National Agency for Food Drug Administration and Control (NAFDAC)( Plot 1, Isolo Industrial Scheme, Oshodi-Apapa Expressway, Isolo, Lagos, Nigeria; +234 (0)9 523-8367; der.headquarters@nafdac.gov.ng), ref: NAFDAC/DER/VCTD/IVON-PP/2022/01 4. Approved 26/07/2022, Lagos State Ministry of Health (LSMH) (Block 4, The Secretariat, Alausa, Ikeja, P.M.B 21007, Ikeja; no telephone number provided; health.lagosstate.gov.ng) ref: LSMH/6649/I/120 5. Approved 30/06/2022, Rivers State Health Research Ethics Committee (26 Okoroma street, Port Harcourt, Nigeria; +234 (0)84230828; rshmbph@yahoo.com), ref: RSHMB/RSHREC/2022/021 6. Approved 08/07/2022, Kano State of Nigeria Ministry of Health, Health Research Ethics Committee (2nd & 3rd floor, Post Office road, Kano State, Nigeria; +234 (0)8039472476; moh.kano2019@gmail.com), ref: NHREC/17/03//2018 7. Approved 20/07/2022, University of Port Harcourt Teaching Hospital Research Ethics Committee (P.M.B 6176, Port Harcourt, Nigeria; no telephone number provided; no email provided), ref: UPTH/ADM/90/S.II/VOL.XI/1394) 8. Approved 04/08/2022, Kwara State Ministry of Health Ethical Research Committee (ERC) (P.M.B 1386, Fate road, Ilorin, Kwara state, Nigeria; no telephone number provided; no email provided) ref: ERC/MOH/2022/08/068 |
| Condition | Iron deficiency anaemia in postpartum women |
| Intervention | Postpartum women during 6-48 hours of delivery will be screened. Eligible women on the ward will be individually randomized in a 1:1 ratio to receive either intravenous ferric carboxymaltose or oral iron. The baseline biodata of the participant will be entered into "REDCap" and "Sealed envelope" will generate the randomisation code for each participant. The drugs have been pre-supplied and stored according to the manufacturer's standard on site. Research staff depending on the arm the participant is randomised into will administer the drug. The intervention group will receive ferric carboxymaltose, a single dose of 20 mg/kg up to a maximum of 1000 mg. This dose will be administered as an infusion in 200 ml 0.9% sodium chloride and infused over a minimum of 15 - 20 minutes. Thereafter, they will be observed closely for a minimum of 30 minutes after infusion. The control group will receive oral ferrous sulphate 200 mg (65 mg elemental iron), to be taken two times daily; 1 hour before meals or 2 hours after meals with a full glass of water till 6 weeks postpartum. All participants will be followed up subsequently till 6 months postpartum. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Intravenous ferric carboxymaltose, oral ferrous sulphate |
| Primary outcome measure | Current primary outcome measure as of 31/07/2024: Proportion of participants who are anemic at six weeks postpartum. An anemic state is defined as hemoglobin level of < 11.0 g/dL, measured using haemoglobin levels at 6weeks postpartum ____ Previous primary outcome measure: Proportion of participants who are non-anaemic at six weeks postpartum. Non-anaemic state is defined as haemoglobin level ≥ 11.0g/dl, measured using haemoglobin levels at 6weeks postpartum |
| Secondary outcome measures | 1. Proportion of women with postpartum depression, measured using the Edinburgh Postnatal Depression Scale at six weeks and six months postpartum. 2. Change in mean postpartum haemoglobin levels at two weeks and six weeks postpartum, measured using haemoglobin levels at two weeks and six weeks. 3. Achievement of a non-anaemic state (Hb≥11.0g/dl) at six months postpartum, measured using haemoglobin levels at six months. 4. Prevalence of moderate/severe anaemia at six weeks and six months postpartum, measured using haemoglobin levels at six weeks and six months. Moderate anaemia is defined as haemoglobin level 7.0-9.9 g/dl and severe anaemia as haemoglobin level 5. Change in mean serum ferritin, serum transferrin, serum iron and % transferrin saturation at two weeks and six weeks postpartum. 6. Need for blood transfusion after iron treatment during the first 6 weeks postpartum. 7. Prevalence of fatigue at six weeks and six months postpartum, measured using the Fatigue Severity Scale (revised FSS-5R version). 8. Proportion of women with secondary postpartum haemorrhage after treatment. This will be defined as excessive bleeding requiring surgical intervention or blood transfusion from 24 hours after delivery till 12 weeks postpartum. 9. Proportion of infants being breastfed (exclusive and any) at six weeks and six months postpartum. 10. Prevalence of impaired maternal-infant bonding at six weeks and six months postpartum measured using the Mother-to-Infant Bonding Scale at six weeks and six months postpartum. 11. Incidence confirmed or suspected maternal infection within 6 weeks of birth, as defined by a new prescription of antibiotics for presumed perineal wound-related infection, endometritis or uterine infection, urinary tract infection or other systemic infection (clinical sepsis). 12. Incidence of hypophosphatemia at two weeks and six weeks postpartum. Measurement of vitamin D, alkaline phosphatase, P1NP, FGF23, Ca, PO4, which are biomarkers of phosphorus homeostasis and bone turnover at two weeks and six weeks postpartum. Hypophosphatemia is defined as serum phosphate level < 1 mg/dL (0.32 mmol/L). 13. Incidence of early neonatal death, defined as death of new-born from enrolment of the mother to before 7 completed days. 14. Incidence of late neonatal death, defined as death of the new-born from enrolment of the mother to before 28 completed days. 15. Incidence of infant death, defined as death from enrolment before the age of six months. 16. Incidence of post-natal maternal death from enrolment up to 6 weeks and at 6 months postpartum. 17. Incidence of adverse drug events. 18. Quality of life measured using the WHOQOL BREF at enrolment, 6 weeks, and 6 months postpartum. |
| Overall study start date | 01/02/2022 |
| Overall study end date | 18/12/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 15 Years |
| Upper age limit | 49 Years |
| Sex | Female |
| Target number of participants | 1400 |
| Total final enrolment | 1400 |
| Participant inclusion criteria | 1. Women aged between 15 and 49 years 2. Between 6 and 48 hours after delivery 3. Baseline (enrollment) moderate or severe anemia (Hb ≤ 9.9g/dl), confirmed by Hemocue haemoglobinometer 4. Able and willing to give written informed consent |
| Participant exclusion criteria | 1. Having received a blood transfusion, for any indication, within the last 3 months 2. Symptomatic anemia and a need for urgent correction 3. Known haemoglobinopathy such as sickle cell disease, HbCC disease 4. Clinically confirmed malabsorption syndrome 5. Known hypersensitivity or contraindication to any form of iron treatment, study drug or any of its excipients 6. Self-reported pre-existing maternal depression or other psychiatric illness and as evidenced by a YES response to any past history of psychiatry ward hospitalization, psychiatry medications, behavioral changes, or past consultation with psychiatry services 7. Severe allergic conditions such as severe asthma, eczema or other atopic condition 8. Known autoimmune conditions e.g., systemic lupus erythematosus, rheumatoid arthritis or known severe drug allergies. 9. Planning to move or reside outside the research area |
| Recruitment start date | 28/11/2022 |
| Recruitment end date | 03/07/2024 |
Locations
Countries of recruitment
- Nigeria
Study participating centres
Lagos
100254
Nigeria
Festac Town
Amuwo-Odofin
Lagos
102102
Nigeria
Surulere
Lagos
101283
Nigeria
Iju Road
Ifako-Ijaye
Lagos
101232
Nigeria
Idimu
Lagos
100278
Nigeria
Port Harcourt
Rivers
500102
Nigeria
Rivers
501101
Nigeria
Bori
Notem
Rivers
502101
Nigeria
Omoku
Rivers
510101
Nigeria
Abuloma
Port Harcourt
Rivers
500102
Nigeria
Kano
700233
Nigeria
Kano
700252
Nigeria
Kofar Nassarawa
Kano
700224
Nigeria
Kano
700271
Nigeria
Kofar Dukayuwa
Kano
700282
Nigeria
Oke Ose
Ilorin
Kwara
241102
Nigeria
Ilorin
Kwara
240101
Nigeria
Along Yebmot Hotel
Ilorin
Kwara
240101
Nigeria
Ilorin
Kwara
240101
Nigeria
Ilorin
Kwara
240101
Nigeria
Sponsor information
University/education
College of Medicine
Lagos
12003
Nigeria
| Phone | +234 (0)8023002960 |
|---|---|
| provost@cmul.edu.ng | |
| Website | http://www.unilag.edu.ng/ |
"ROR" |
https://ror.org/05rk03822 |
Funders
Funder type
Charity
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | 30/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | The study results will be used in preparing charts for health education and counselling of women at the antenatal clinics and postnatal wards. The findings of the study will be presented at conferences (both international and local) to disseminate them to a large body of professionals in the field of obstetrics and gynaecology, haematology, internal medicine, paediatrics, etc. The findings will also be published in high-impact peer-reviewed journals for wider dissemination of information. Press releases about the findings of the study will be issued. |
| IPD sharing plan | The researchers will deposit the research data in the Open Science Framework. The data will be deidentified to maintain participants' confidentiality. The data will be shared at the time of publication of the first manuscript. This will likely be done within 6 months of study completion. The duration of IPD sharing will be 2 years. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.1 | 03/10/2022 | No | Yes | |
| Protocol file | version 1.3 | 26/09/2022 | 03/10/2022 | No | No |
| Protocol file | version 1.4 | 30/11/2022 | 09/02/2023 | No | No |
| Protocol file | version 2.0 | 18/01/2024 | 12/03/2024 | No | No |
| Statistical Analysis Plan | 13/03/2025 | 04/04/2025 | No | No |
Additional files
Editorial Notes
04/04/2025: The statistical analysis plan was uploaded as an additional file.
29/01/2025: The overall end date was changed from 28/02/2025 to 18/12/2024.
13/08/2024: The recruitment end date was changed from 31/08/2024 to 03/07/2024.
31/07/2024: The primary outcome measure was changed.
03/07/2024: The total final enrolment was added.
12/03/2024: The following changes were made to the trial record:
1. Uploaded protocol v2.0 (not peer-reviewed) as an additional file.
2. The recruitment end date was changed from 30/03/2024 to 31/08/2024.
3. The overall end date was changed from 30/09/2024 to 28/02/2025.
4. The plain English summary was updated to reflect these changes.
09/02/2023: The following changes were made to the trial record:
1. The recruitment start date was changed from 31/10/2022 to 28/11/2022.
2. The recruitment end date was changed from 28/02/2023 to 30/03/2024.
3. The overall end date was changed from 31/03/2025 to 30/09/2024.
3. The intention to publish date was changed from 30/06/2025 to 30/12/2025.
4. The plain English summary was updated to reflect these changes.
5. Uploaded protocol v1.4 (not peer-reviewed) as an additional file.
03/10/2022: Trial's existence confirmed by National Health Research and Ethics Committee of Nigeria
