Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202012843695208 Date of Approval: 08/12/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The use of iron administered as an infusion into a vein compared to the use of iron tablets taken by mouth for treating Nigerian women with iron deficiency anaemia during pregnancy (IVON trial)
Official scientific title Intravenous versus oral iron for iron deficiency anemia in pregnant Nigerian women (IVON): an open label, randomized controlled trial (IVON trial)
Brief summary describing the background and objectives of the trial Background: Anaemia in pregnancy is a public health burden with high incidence in Africa. Currently high dose oral iron is recommended for treatment of mild to moderate anaemia and blood transfusion for severe anaemia. The high dose oral iron is often poorly tolerated and associated with several side effects. Various parenteral iron preparations are now available for treatment of iron deficiency anaemia (IDA). The earliest of these, iron dextran is not commonly used because of its potential to cause anaphylactic reactions. Newer preparations have been found to be safer and their use for treatment of IDA is currently being evaluated. Objective: This study sought out to compare the effectiveness of intravenous ferric carboxymaltose (intervention) versus oral ferrous sulphate (control) for treating IDA in pregnancy and to compare the tolerability, safety and the cost-effectiveness of intravenous versus oral iron among pregnant Nigerian women with moderate and severe IDA at 20–32 weeks’ gestation. Methodology: This study will be a hybrid Type 1 effectiveness-implementation design. A total of 1056 eligible and consenting pregnant women with anaemia at 20 – 32 weeks gestation will be recruited. They will be randomized into either of 2 groups. Group A will have intravenous ferric carboxymaltose 20mg/kg to a maximum of 1000mg infusion over 15 – 20 minutes at enrolment. Group B will have oral ferrous sulphate 200mg (65mg elemental iron) thrice daily from enrolment till delivery. They will be followed up through delivery and until 6 weeks post partum. Their haemoglobin concentration, full blood count, serum ferritin and iron panel comprising serum iron, serum ferritin, transferrin saturation and total iron binding globulin, will be assayed at specific intervals using standard laboratory techniques. Depression will be assessed at each visit using Edinburg Postnatal Depression Scale. Cost effectiveness analysis will also be done at each visit. The primary outcome measure will be prevalence of maternal anaemia at 36 weeks and preterm birth. Secondary outcome measures will include safety and tolerability of trial drugs, severe maternal events, incidence of infant low birth weight and incidence of depression. Statistical analysis will be done using STATA version 16.0 statistical software (STATACorp, Texas, USA).
Type of trial RCT
Acronym (If the trial has an acronym then please provide) IVON trial
Disease(s) or condition(s) being studied Haematological Disorders,Nutritional, Metabolic, Endocrine,Obstetrics and Gynecology,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Maternal anaemia, preterm birth, maternal depression and low birth weight
Purpose of the trial Treatment: Drugs
Anticipated trial start date 04/01/2021
Actual trial start date 09/08/2021
Anticipated date of last follow up 09/07/2023
Actual Last follow-up date 15/06/2023
Anticipated target sample size (number of participants) 1056
Actual target sample size (number of participants) 1056
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
NCT04976179 Clinicaltrial.gov
ISRCTN63484804 International Standard Randomised Controlled Trial Number
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Intravenous ferric carboxymaltose 20mg/kg to a maximum of 1000mg infusion over 15 - 20 minutes at enrolment. single dose at enrolment. Intravenous ferric carboxymaltose given at a dose of 20mg/kg to a maximum of 1000mg infusion diluted in 200mls of 0.9% Normal saline given over 15 - 20 minutes at enrolment. 528
Control Group Oral ferrous sulphate 200mg (65mg elemental iron) 3 times daily till 6 weeks post delivery. From enrolment till 6 weeks post delivery. Oral ferrous sulphate given at a dose of 200mg (65mg elemental iron) 3 times a day from enrolment till delivery. 528 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Pregnant women aged 15 to 49 years old. 2. Gestational age 20- and 32-weeks. 3. Baseline (enrollment) laboratory-confirmed moderate or severe anemia (Hb < 10g/dl). 1. Medically-confirmed significant bleeding, major surgery or received blood transfusion within the last 3 months 2. Symptomatic anemia with dyspnea or fatigue and a need for urgent correction 3. Concurrent anemia of another cause besides IDA. 4. Clinically-confirmed malabsorption syndrome or hypersensitivity to any form of iron treatment. 5. Preexisting maternal depression or other psychiatric illness 6. History of any immune related illness e.g., SLE, Rheumatoid arthritis. 7. Severe allergic reactions such as severe asthma. 8. Women with known drug allergies Adult: 19 Year-44 Year 15 Year(s) 49 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 02/12/2020 LAGOS UNIVERSITY TEACHING HOSPITAL HEALTH AND RESEARCH ETHICS COMMITTEE
Ethics Committee Address
Street address City Postal code Country
Idi-Araba Lagos 100254 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 04/02/2021 National Health Research and Ethics Committee NHREC
Ethics Committee Address
Street address City Postal code Country
Federal Ministry of Health, 11th floor, Federal Secretariat Complex Phase III, Ahmadu Bello Way, Abuja Abuja 900001 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 20/01/2021 Aminu Kano Teaching Hospital AKTH Health Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Zaria Road, Kano Kano 700225 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/12/2020 Lagos State Health Service Commission
Ethics Committee Address
Street address City Postal code Country
Ganiyu Smith Street, Lagos Island Lagos Island 101282 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/12/2020 Lagos State Primary Health care Board
Ethics Committee Address
Street address City Postal code Country
Taylor Drive, Off Edmund Street, Yaba Lagos Mainland 101212 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/11/2020 Ministry of Health Kano
Ethics Committee Address
Street address City Postal code Country
Post Office Road, Kano Kano 700213 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 23/04/2021 National Agency for Drug Administration and Control NAFDAC
Ethics Committee Address
Street address City Postal code Country
Plot 1, Isolo Industrial Estate, Oshodi-Isolo Expressway, Lagos Lagos 100263 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/07/2021 Lagos University Teaching Hospital Health Research and Ethics Committee LUTH HREC
Ethics Committee Address
Street address City Postal code Country
Idi-Araba, Lagos Lagos 100254 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 31/03/2022 National Health Research Committee of Nigeria NHREC
Ethics Committee Address
Street address City Postal code Country
Ahmadu Bello Way, Abuja Abuja 900288 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. The comparative effectiveness of treatment with intravenous ferric carboxymaltose (intervention) versus oral ferrous sulphate (control) in reducing the prevalence of maternal anemia at 36 weeks' gestation. 2. Reducing the incidence of preterm birth. Hb concentration will be measured at 36 weeks gestational age. Data for incidence of preterm birth will be obtained at delivery.
Secondary Outcome 1. Increase in maternal hemoglobin levels at 4 weeks post-initiation of treatment. 2. The safety and tolerability of intravenous ferric carboxymaltose versus oral ferrous sulphate, including the incidence of hypophosphatemia and severity of maternal adverse effects. 3. Severe maternal events, specifically, haemorrhage, sepsis, shock and the need for blood transfusion. 4. The incidence of low infant birthweight (<2.5 kg), prematurity (<37 weeks’ gestation as dated from the last menstrual period or a first trimester ultrasound scan), stillbirth and neonatal mortality (birth till 28 days of life), and proportion of infants being breastfed at 1, 2 and 4 weeks of life, and receiving BCG, oral polio and hepatitis vaccination in same time period. 5. The incidence of small for gestational age (birthweight less than the 10th percentile for gestational age). 6. Depression linked to emotional well-being of mothers using the validated Edinburgh Postnatal Depression Scale. 7. Prevalence of maternal iron deficiency at 36 weeks gestational age defined as serum ferritin level less than 30ng/mL. Each outcome will be assessed at specified times either at enrolment and/or day 1, 4 weeks, 5 weeks and 36 weeks post enrolment and/or delivery and/or 7 days, 28 days and 6 weeks post delivery.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Lagos University Teaching Hospital Idi-Arba Lagos 100254 Nigeria
Lagos Island Maternity Hospital Campbell street, Lagos Island Lagos 101231 Nigeria
Mother and Child Centre Amuwo Odofin 1st Avenue, 1st Gate, Festac Town, Amuwo-Odofin Lagos 102312 Nigeria
Simpson Primary Health Centre Ebute Metta Simpson street Ebute-Metta Lagos 101212 Nigeria
Iwaya Primary Health Centre Yaba Omotola street, Iwaya Lagos 100213 Nigeria
Aminu Kano Teaching Hospital Zaria road Kano 700233 Nigeria
Sheikh Jeddah General Hospital Bello Road 700224 Sabon Gari West Kano 700271 Nigeria
Nuhu Bammali General Hospital Emir Palace Road 700224 Kan Karofi Kano 713261 Nigeria
Kumbotsu Comprehensive Primary Health Centre Kumbotsu Kano 700104 Nigeria
Sharada Primary Health Centre Sharada Kano 700234 Nigeria
Kabuga Comprehensive Primary Health Centre Gwarzo Rd, Kofar Dukayuwa Kano 700282 Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
BILL AND MELINDA GATES FOUNDATION 500 5TH Ave N Seattle Washington WA, 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Lagos Idi-Araba Lagos Nigeria University
COLLABORATORS
Name Street address City Postal code Country
Professor Bosede B. Afolabi Idi-Araba Lagos 100254 Nigeria
Professor Hadiza Galadanci Zaria road Kano 700233 Nigeria
Dr. Mobolanle Balogun Idi--Araba Lagos 100254 Nigeria
Dr. Titilope Adeyemo Idi-Araba Lagos 100254 Nigeria
Dr. Nadia Sam Agudu 620 W Lexington St Baltimore MD 2120 United States of America
Dr Ochuwa A. Babah Idi-Araba Lagos 100254 Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Bosede Afolabi bosedeafolabi2003@yahoo.com +2348023154064 Idi-Araba
City Postal code Country Position/Affiliation
Lagos 100254 Nigeria Professor Department of Obstetrics and Gynecology Faculty of Clinical Sciences College of Medicine University of Lagos and Lagos University Teaching Hospital IdiAraba Lagos
Role Name Email Phone Street address
Public Enquiries Ochuwa Babah ochuwab@yahoo.co.uk +2347038090032 Idi-Araba
City Postal code Country Position/Affiliation
Lagos 100254 Nigeria Senior Lecturer Department of Obstetrics and Gynecology Faculty of Clinical Sciences College of Medicine University of Lagos and Lagos University Teaching Hospital IdiAraba Lagos
Role Name Email Phone Street address
Scientific Enquiries Bosede Afolabi bosedeafolabi2003@yahoo.com +2348023154064 Idi-Araba
City Postal code Country Position/Affiliation
Lagos 100254 Nigeria Professor Department of Obstetrics and Gynecology Faculty of Clinical Sciences College of Medicine University of Lagos and Lagos University Teaching Hospital Lagos
Role Name Email Phone Street address
Scientific Enquiries Hadiza Galadanci hgaladanci@yahoo.com +2348033210047 Zaria Road, Kano
City Postal code Country Position/Affiliation
Kano 700233 Nigeria Co Investigator
Role Name Email Phone Street address
Public Enquiries Abubakar Abdulazeez aabdulazeez459@gmail.com +2348036430171 Zaria Road, Kano
City Postal code Country Position/Affiliation
Kano 700233 Nigeria Program Manager IVON trial Kano Zone
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We will store the data and deposit it in ‘Open Science Framework’, after approval is obtained from the ethics committee. We will also provide metadata along with the data to describe it. No patient identifier will be included in data shared. Potential new users may access our data including the metadata on the ‘Open Science Framework’. We will share the data at the time of publication of our first paper. The assigned DOI number, the OSF website details and our approach to data sharing will be included as an appendix to all publications emanating from this research to facilitate accessibility to our data and metadata. We will also share these at any conference presentation both international and local, and also on our study website to facilitate access to it by other researchers. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol The IPD sharing will commence at the time of the first publication or within 6 months of completing the study. The duration of IPD sharing will be 2 years. The tentative start date for IPD sharing is 1st January 2024 and the tenative end date is 31st December 2025. 1. The principal investigator will bear overall responsibility for this data and will be responsible for deciding whether to supply research data to a potential new user. The CMUL HREC will provide an independent oversight function. 2. Data will be made available at the time of publication, at the latest. Depending on the nature of the data itself, data may be made available earlier, either on an individual basis to interested researchers and/or potential new collaborators. 3. We will ensure that our informed consent forms clearly spell out and seek consent for future data sharing. However, only de-identified data will be shared. I think we will need to clearly spell out the data sharing process. 4. All external users will sign and be bound by our data sharing agreements and will not be allowed to use the data for reasons other than stated in their application. 5. IPD sharing will be by open access on Open Science Framework during the period of IPD sharing.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://ivontrial.com/ No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information