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

Study Overview
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Brief Summary
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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 18 months. Approximately 600 participants will be enrolled. The primary hypothesis is that the mean change in hemoglobin concentration will be significantly higher in the group assigned to the LNG IUS compared to the group assigned to COCs

Detailed Description
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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.

Official Title
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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

Conditions
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Anemia

Intervention / Treatment
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* Diagnostic Test: Measure hemoglobin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LNG IUS<br>Levonorgestrel intrauterine system | Diagnostic Test: Measure hemoglobin<br>* Venous blood sample will be taken from the arm<br>* Other names: Measure serum ferritin;|
| Active Comparator: COC<br>Combined oral contraceptives with ferrous fumarate tables in regimen | Diagnostic Test: Measure hemoglobin<br>* Venous blood sample will be taken from the arm<br>* Other names: Measure serum ferritin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin | Measured in g/L | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum ferritin | Measured in mcg/L | 18 months | 
| Change in number of days of bleeding/spotting in a 28-day menstrual cycle | A bleeding day is defined as a day when blood loss requires the use of sanitary protection with a tampon, pad or pantyliner. A spotting day is a non-bleeding day with minimal blood loss that does not require new use of any type of sanitary protection, including pantyliners | 18 months | 
| Contraceptive method discontinuation | Discontinuation is defined as either LNG IUS removal or 5 or more consecutive days without taking an oral contraceptive pill | 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. | 18 months |