Reducing Anemia in Pregnancy in India: the RAPIDIRON Trial

NCT05358509 | Completed Phase 4 DMC

• 1 other identifier: 1811-03347
• Study Type: interventional
• Target: 4,368
• Locations: 1 country
• Sites: 4

Brief Summary

Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. Anemia rates are among the highest in South Asia, with a recent national survey indicating that over half of pregnant women in India are classified as anemic. For nearly 40 years, India's first-level treatment for anemia in pregnancy has been oral iron; however, side effects, poor adherence to tablet ingestion, and low therapeutic impact are among reasons to consider a new paradigm for treatment of pregnant women with iron deficiency anemia (IDA). Reducing Anemia in Pregnancy in India: the RAPIDIRON Trial is a 3-arm, randomized-controlled trial designed to assess if a single dose of an intravenous (IV) iron formulation, administered early in the second trimester of pregnancy for treatment of moderate IDA, will result in a greater proportion of participants in the IV iron arms achieving a normal hemoglobin concentration in the third trimester when compared to participants randomized to receive oral iron. This trial is also designed to test the hypothesis that the low birth weight (LBW) rate for participants randomized to the IV iron arms will be lower when compared to the LBW rate of those randomly assigned to the oral iron arm. The three arms include two IV iron arms (arm 1 - ferric carboxymaltose, arm 2 - iron isomaltoside, also known as ferric derisomaltose) and an active, comparator arm receiving oral iron, which is the standard of care. This study will be conducted in two states in India - Karnataka and Rajasthan. This study supports the overall goals of the Indian Ministry of Health and Family Welfare for pregnancy care; thus, all study participants will be followed according to the Ministry's antenatal care guidelines, and data will be collected through 42 days post-delivery. (see attached protocol for more detail)

Conditions

Iron Deficiency Anemia; Infant, Low Birth Weight; Anemia of Pregnancy

Keywords

Anemia; Iron Deficiency Anemia; Intravenous iron; India; Low birth weight infants; Anemia in pregnancy

Outcome Measures

Primary Outcomes (2)

• Return to non-anemic status in the last trimester of pregnancy

  Return to non-anemic status, defined as hemoglobin concentration ≥11 g/dL, measured at either a 30-34 week antenatal visit or prior to delivery

  30-34 week antenatal visit or prior to delivery

• Low birth weight (<2500 grams) deliveries

  Low birth weight (\<2500 grams) deliveries

  Delivery/birth

Secondary Outcomes (26)

• Changes in hemoglobin concentration by moderate anemia subgroups

  30-34 week antenatal visit or prior to delivery

• Changes in transferrin saturation

  After randomization to 42 days post-delivery

• Changes in ferritin

  After randomization to 42 days post-delivery

• Changes in offspring hemoglobin measured from cord blood

  Delivery/birth

• Offspring transferrin saturation from cord blood

  Delivery/birth

Other Outcomes (1)

• An independent cost-effectiveness analysis will be conducted by an expert in the field with a background in health economics and the cost-effectiveness of health care interventions.

  After randomization to 42 days post-delivery

Study Arms (3)

IV iron intervention arm 1

EXPERIMENTAL

Intervention arm 1 involves a single dose of an IV iron formulation - ferric carboxymaltose - given during pregnancy.

Drug: Ferric carboxymaltose

IV iron intervention arm 2

EXPERIMENTAL

Intervention arm 2 involves a single dose of an IV iron formulation - iron isomaltoside - given during pregnancy.

Drug: Iron isomaltoside

Active comparator

ACTIVE COMPARATOR

Participants randomly assigned to the active comparator arm will receive oral iron tablets to take daily, which is the current standard of care.

Drug: Ferric Sulfate

Interventions

Ferric carboxymaltose DRUG

Pregnant participants randomized to intervention arm 1 will receive a single dose of ferric carboxymaltose having 1000mg of iron if they weigh over 50kg. If a participant is under 50kg, they will receive a lower dose as determined by a formula used by the manufacturer (20mg iron/kg body weight). This will be given ideally immediately after randomization, sometime between 14 weeks and 17 weeks of pregnancy.

IV iron intervention arm 1

Iron isomaltoside DRUG

Pregnant participants randomized to intervention arm 1 will receive a single dose of iron isomaltoside having 1000mg of iron if they weigh over 50kg. If a participant is under 50kg, they will receive a lower dose as determined by a formula used by the manufacturer (20mg iron/kg body weight). This will be given ideally immediately after randomization, sometime between 14 weeks and 17 weeks of pregnancy.

Also known as: Ferric derisomaltose

IV iron intervention arm 2

Ferric Sulfate DRUG

Pregnant participants randomized to the oral iron arm will be given 200 ferrous sulphate tablets with 60mg elemental iron each, immediately after randomization, and instructed to take two per day (one in the morning and one at night) throughout the remainder of their pregnancy.

Also known as: Ferric sulphate

Active comparator

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women between 18-40 years of age at time of consent that received education about the study and were capable of giving informed consent;
• Hemoglobin concentration of 7 - 10.4 g/dL;
• Expressed intent and expectation of remaining in the designated research area during pregnancy and delivering in a facility in or near the research area and remaining in the area to enable study participant and data collection consistent with the research protocol;
• Expressed willingness that specifically includes agreement to randomization to the standard care study arm (of oral iron) or to one of the two arms involving treatment with single-dose IV iron.
• Iron deficiency anemia, defined for this study as moderate anemia with hemoglobin concentration level between 7 - 9.9 g/dL, serum transferrin saturation (TSAT) \<20%, and/or ferritin \<30 ng/mL;
• Presence of a live, singleton, intrauterine fetus and dating ultrasound (at visit #2) that indicates a pregnancy that, at randomization, would be between the beginning of week 14 and prior to 17 weeks 0 days.

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Children's Investment Fund Foundation: collaborator
• Jawaharlal Nehru Medical College: collaborator
• S. Nijalingappa Medical College: collaborator
• Raichur Institute of Medical Sciences: collaborator
• Sawai Mansingh Medical College: collaborator

Study Sites (4)

S. Nijalingappa Medical College

Bagalkot, Karnataka, India

Location

Jawaharlal Nehru Medical College

Belagavi, Karnataka, India

Location

Raichur Institute of Medical Sciences

Rāichūr, Karnataka, India

Location

Sawai Man Singh Medical College

Jaipur, Rajasthan, India

Location

Related Publications (4)

• International Institute for Population Sciences (IIPS). National Family Health Survey-5, 2019-21, India Fact Sheet. Retrieved 8 February 2022 from: http://rchiips.org/nfhs/NFHS-5_FCTS/India.pdf.

  BACKGROUND

• Ministry of Health and Family Welfare, Government of India. (April 2018). Anemia Mukt Bharat - Intensified National Iron Plus Initiative (I-NIPI) - Operational Guidelines for Programme Managers. Retrieved 13 April 2022 from: https://anemiamuktbharat.info/wp-content/uploads/2019/09/Anemia-Mukt-Bharat-Operational-Guidelines-FINAL.pdf.

  BACKGROUND

• electronic medicines compendium (emc). Ferinject (ferric carboxymaltose). Retrieved 30 July 2020 from: https://www.medicines.org.uk/emc/product/5910/.

  BACKGROUND

• electronic medicines compendium (emc). Monofer 100mg/ml solution for injection/infusion. Retrieved 30 July 2020 from: https://www.medicines.org.uk/emc/product/5676/smpc.

  BACKGROUND

Related Links

• Anemia Mukt Bharat - India National Anemia Guidelines for Program Managers
• Ferinject (ferric carboxymaltose) - Summary of Product Characteristics
• Monofer 100mg/ml solution for injection/infusion - Summary of Product Characteristics

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Anemia

Interventions

ferric carboxymaltose; iron isomaltoside 1000; ferric derisomaltose; ferric sulfate

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Richard Derman, MD, MPH

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Oral iron use will not be masked (as tablets will be provided). However, blinding will occur for the two IV iron intervention arms, as participants, primary health center (PHC) staff, and community health center (CHC) infusion teams will only know that participants have been randomly assigned to receive an IV iron infusion without knowing the specific arm and formulation to be used. A pharmacist associated with each CHC performing infusions for the trial will be designated to prepare the randomly assigned IV iron formulation (according to participant weight and manufacturer instructions) on the day of treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3-arm, randomized-controlled trial involving two intervention arms (two formulations of intravenous iron) and one active, comparator arm (oral iron, standard of care). Pregnant participants will be randomized with a one-to-one-to-one ration to the three study arms.

Study Record Dates

• First Submitted: April 15, 2022
• First Posted: May 3, 2022
• Study Start: March 15, 2021
• Primary Completion: December 14, 2023
• Study Completion: January 21, 2024
• Last Updated: May 24, 2024

Record last verified: 2024-05

Locations

IN (4)