Iron Infusion Into a Vein Compared to Iron Tablet Taken by Mouth for Treating Iron Deficiency Anemia in Pregnancy (IVON)

NCT04976179 | Completed Phase 3 DMC

• 4 other identifiers: PACTR202012843695208ISRCTN63484804Investment ID INV-0172712021-002867-23
• Study Type: interventional
• Target: 1,056
• Locations: 1 country
• Sites: 11

Brief Summary

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. 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 in 200mls of normal saline 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 serum transferrin 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 incidence of maternal anaemia and rise in haemoglobin level. 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).

Conditions

Iron Deficiency Anemia of Pregnancy

Keywords

anaemia in pregnancy; iron deficiency; ferric carboxymaltose; ferrous sulphate; intravenous; oral; side effects; effectiveness

Outcome Measures

Primary Outcomes (2)

• Prevalence of maternal anemia at 36 weeks' gestation

  To be collected from data source on number of women with hemoglobin concentration less than 10g/dl as determined by hemocue.

  Measurement taken at 36 weeks gestational age

• Incidence of preterm delivery

  Measured using data source. Preterm delivery is defined as all births after 28 weeks gestational age but before 37 completed weeks of gestation.

  Data will be collected following delivery.

Secondary Outcomes (6)

• Proportion of patients with side effects or intolerance to medication in FCM vs. FS group, including incidence of hypophosphatemia and severe maternal adverse effects at Day 1 and 4 weeks post enrolment, at 36 weeks gestation and 6 weeks post delivery

  Assessment to be done on Day 1 and 4 weeks post enrolment, at 36 weeks gestational age and at 6 weeks post delivery

• Proportion of patients with severe maternal events, specifically, haemorrhage, sepsis, shock and the need for blood transfusion measured using data source at delivery

  Measured at delivery

• The incidence of low infant birthweight, prematurity, stillbirth and neonatal mortality, 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

  Measurements will be taken at delivery, 1,2 and 4 weeks post delivery

• The incidence of depression linked to emotional well-being of mothers using the validated Edinburgh Postnatal Depression Scale measured at enrolment, 36 weeks gestational age and 7 days post delivery

  Measurements taken at enrolment, 36 weeks gestational age and 7 days post delivery

• Maternal hemoglobin levels at 4 weeks post-initiation of treatment

  Measurement taken at 4 weeks post-initiation of treatment

Study Arms (2)

FCM - Intravenous Ferric carboxymaltose

EXPERIMENTAL

Intravenous Ferric Carboxymatlose administered in a single dose of 20mg/Kg to a maximum of 1000mg in 200mls of infusion given over minimum of 15 - 20 minutes at enrollment.

Drug: Ferric carboxymaltose

FS -Oral Ferrous sulphate

ACTIVE COMPARATOR

Oral Ferrous Sulphate (containing 65mg of elemental iron) to be taken as one 200mg tablet 3 times a day until delivery.

Drug: Ferrous sulfate

Interventions

Ferric carboxymaltose DRUG

Ferric carboxymaltose to be given as an intravenous infusion

Also known as: Ferinject

FCM - Intravenous Ferric carboxymaltose

Ferrous sulfate DRUG

Ferrous sulphate tablet to be taken orally

Also known as: Fesulf

FS -Oral Ferrous sulphate

Eligibility Criteria

• Age: 15 Years - 49 Years
• Gender Eligibility Details: Pregnant females only are eligible to participate in the proposed research.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pregnant women aged 15 to 49 years old between 20\*- and 32\*\*-weeks' gestational age.
• Baseline (enrollment) laboratory-confirmed moderate or severe anemia (Hb \< 10g/dl).

You may not qualify if:

• Medically-confirmed significant bleeding, major surgery or received blood transfusion within the last 3 months.
• Severe symptomatic anemia needing urgent correction with blood transfusion.
• Anemia of other cause besides IDA e.g., Sickle cell anemia.
• Clinically-confirmed malabsorption syndrome.
• Hypersensitivity to any form of iron treatment.
• History of any immune related illness e.g., SLE, Rheumatoid arthritis.
• Preexisting maternal depression or other psychiatric illness.
• Severe allergic reactions such as severe asthma.
• History of severe drug allergy.

Sponsors & Collaborators

• University of Lagos, Nigeria: lead
• Aminu Kano Teaching Hospital: collaborator

Study Sites (11)

Kabuga Comprehensive Primary Health Centre

Gwarzo, Kano State, 700282, Nigeria

Location

Kumbotso Comprehensive Health Centre

Kumbotso, Kano State, 700104, Nigeria

Location

Aminu Kano Teaching Hospital

Tarauni, Kano State, 700233, Nigeria

Location

Simpson Primary Health Centre

Ebute-Metta, Lagos, 101212, Nigeria

Location

Lagos University Teaching Hospital

Idi Araba, Lagos, 100254, Nigeria

Location

Iwaya Primary Health Centre

Iwaya, Lagos, 100213, Nigeria

Location

Sheikh Jidda General Hospital

Kano, 700224, Nigeria

Location

Nuhu Bammali Maternity Hospital

Kano, 700231, Nigeria

Location

Sharada Primary Health Centre

Kano, 700234, Nigeria

Location

Mother and Child Centre, Amuwo-Odofin, Lagos

Lagos, 102102, Nigeria

Location

Lagos Island Maternity Hospital, Lagos

Lagos, 102273, Nigeria

Location

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MeSH Terms

Conditions

Iron Deficiencies

Interventions

ferric carboxymaltose; ferrous sulfate

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Bosede B Afolabi, DM(Notts)

  College of Medicine, University of Lagos, Idi-araba, Nigeria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomized using Sealed Envelope software and assigned into 2 parallel study arrms as they are recruited. Those in the FCM group will receive Intravenous Ferric Carboxymaltose (Interventional drug) and those in the FS group will receive Oral Ferrous Sulphate (Standard drug).

Study Record Dates

• First Submitted: July 4, 2021
• First Posted: July 26, 2021
• Study Start: August 9, 2021
• Primary Completion: April 5, 2023
• Study Completion: June 15, 2023
• Last Updated: July 21, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD sharing will commence at the time of first publication or within 6 months of study completion. The duration of IPD sharing will be 2 years, starting tentatively on 1st January 2024 and ending in 31st December 2025.
• Access Criteria: 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.

Locations

NG (11)