Levonorgestrel Intrauterine System Effects on Hemoglobin and Serum Ferritin Among Anemic Women in Kenya (LISA)

Levonorgestrel Intrauterine System Effects on Hemoglobin and Serum Ferritin Among Anemic Women in Kenya: an Open Label Randomized Trial to Compare With an Oral Contraceptive Regimen That Provides Supplemental Ferrous Fumarate Tablets

Women with mild/moderate anemia who are seeking contraception will be randomized to a levonorgestrel (LNG) intrauterine system (IUS) or an LNG/ethinyl estradiol (EE)/ferrous fumarate combined oral contraceptive (COC) regimen and followed prospectively for 12-18 months. Approximately 400 participants will be enrolled. The primary hypothesis that the mean change in hemoglobin in the group assigned to the LNG IUS will be superior to the COC/ferrous fumarate (control) group after 12-months of product use.

Study Overview

• Status: Active, not recruiting
• Conditions: Anemia
• Intervention / Treatment: Device: LNG IUS; Drug: COCs

Detailed Description

Anemia continues to disproportionately affect marginalized women in resource-poor countries. In Africa/SE Asia, over 270 million women of reproductive age are anemic. Iron deficiency anemia causes 18% of maternal deaths worldwide. Multiprong approaches are needed to reduce the prevalence of anemia and the negative impact on family health.

Every menstrual cycle, women lose 14 to 19 mg of iron; this is iron that anemic women need to lead healthier lives. Though the relationships between iron loss from menstruation, absorption of dietary intake of iron, storing iron, and the impacts on hematologic parameters are complex, higher levels of menstrual blood loss are associated with lower hemoglobin values.

The levonorgestrel intrauterine system is a highly effective contraceptive product that also generally reduces menstrual blood loss. In research spanning over four decades, the product consistently raises hemoglobin levels and increases iron stores in broad populations of women, but particularly for women with heavy menstrual bleeding. This product is not widely available in resource-poor countries, due to higher costs relative to other contraceptives.

As a potential tool to alleviate anemia, the levonorgestrel intrauterine system has never been adequately tested. Previous research has never focused on anemic women, nor used proper scientific approaches to determine if the product can significantly increase hemoglobin and iron levels via reducing menstrual blood loss.

The overall goal of the proposed research is to give anemic women in Kenya an opportunity to try the levonorgestrel intrauterine system and with improved scientific approaches, measure the impact on hemoglobin and iron stores. In this randomized trial, the comparison product will be oral contraceptives containing iron supplement pills. If the levonorgestrel intrauterine system is found to work as hypothesized, then the product can become another tool to alleviate anemia among reproductive-aged women, resulting in healthier living and healthier beginnings to pregnancy when desired.

• Study Type: Interventional
• Enrollment (Actual): 405
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Nairobi, Kenya
    • Kangemi Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Provide sequential oral and written consents to screen for eligibility and enroll
• Female, aged 18-50
• Desire to use contraception or possibly switch methods
• Possession of a cell phone and willingness to be contacted
• Confirmatory low hemoglobin (minimum of 87 g/L and maximum of 126 g/L) taken 1 to 4 weeks after the initial test
• Regularly menstruating (at least once every 35 days)
• At least 6 weeks postpartum
• Willingness to agree to study procedures
• Willingness to be randomized to treatment
• Willingness to use assigned hormonal contraceptive for 18 months

Exclusion Criteria:

• Severe anemia (hemoglobin < 86 g/L)
• Currently pregnant based on urine pregnancy test and failure to rule out possible pregnancy according to WHO guidelines
• Surgically sterilized or had a hysterectomy
• Participated previously in this study by being randomized to contraceptive
• Currently using a subdermal contraceptive implant and does not wish to have it removed
• Currently using an LNG IUS
• Currently receiving treatment for anemia
• Any of the following previously diagnosed disorders: hemosiderosis, hemochromatosis, hemolytic anemia
• Known allergic reactions to oral contraceptives or LNG IUS
• Currently receiving an investigational (unapproved) drug in another study
• Any condition (social or medical) which in the opinion of the investigator would make study participation unsafe
• Intending to become pregnant in the next 18 months
• Mucopurulent cervicitis
• Pelvic inflammatory disease
• Other medical contraindications to treatment, according to WHO Medical Eligibility Criteria (categories 3 or 4)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LNG IUS; Levonorgestrel intrauterine system	Device: LNG IUS; Avibela®: Levonorgestrel intrauterine system (LNG IUS) containing 52mg of LNG, released in the uterine cavity at approximately 19mcg per day.
Active Comparator: COC; Combined oral contraceptives with ferrous fumarate tablets in regimen	Drug: COCs; FemiplanTM: Combined oral contraceptives in a 21/7 pill package (21 pills of 0.15 mg of LNG and 30 mcg of EE followed by 7 pills containing 75 mg of ferrous fumarate).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin Level	Measured in g/L	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum ferritin Level	Measured in mcg/L	18 months
Volume of menstrual blood loss and quantity of hygiene products used	Self-report	3, 6, 9, 12, 15, and 18 months
Severe Anemia	Venous hemoglobin less than 86g/L	At 6,12 and 18 months
Contraceptive satisfaction	Level of satisfaction with the products will be recorded on a 5-point Likert scale: very satisfied, somewhat satisfied, neutral, somewhat dissatisfied, very dissatisfied.	12-18 months
Hemoglobin Changes	g/L	18 months

Collaborators and Investigators

• Sponsor: FHI 360
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: David Hubacher, PhD, FHI 360; Principal Investigator: Faith Thuita, PhD, University of Nairobi

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: hemoglobin; anemia; oral contraceptives; hormonal contraception; intrauterine system
• Additional Relevant MeSH Terms: Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Chrysarobin
• Other Study ID Numbers: 1712233; R01HD100497 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated under the project will be shared consistent with the NIH Grant Policy, and the FHI 360 Protection of Human Subjects (PHSC) committee guidelines. Data will be de-identified to avoid linkages to individual research participants and will be free of variables that could lead to deductive disclosure of the identity of individual research participants. A de-identified primary dataset will be posted to an open-data repository within 30 calendar days after the first publication.
• IPD Sharing Time Frame: Deidentified quantitative research data will be made available in a timely manner once the main findings from the research have been accepted for publication.
• IPD Sharing Access Criteria: Data generated under the project will be shared consistent with the NIH Grant Policy, and the FHI 360 Protection of Human Subjects (PHSC) committee guidelines. Data will be de-identified to avoid linkages to individual research participants and will be free of variables that could lead to deductive disclosure of the identity of individual research participants. A de-identified primary dataset will be posted to an open-data repository within 30 calendar days after the first publication.
• IPD Sharing Supporting Information Type: ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No