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.: PACTR202206713343239 Date of Approval: 29/06/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Levonorgestrel Intrauterine System effect on Anemia: LISA Trial
Official scientific title 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.
Brief summary describing the background and objectives of the trial 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. Primary Objective: To compare hemoglobin changes over time in the randomized arms: LNG IUS versus COCs Secondary Objectives: • To compare serum ferritin changes over time in the randomized arms • To correlate changes in hemoglobin and serum ferritin to changes in self-reported menstrual blood loss • To assess and compare participants’ satisfaction with the two contraceptive products • To monitor incidence of progression to severe anemia and compare randomized arms
Type of trial RCT
Acronym (If the trial has an acronym then please provide) LISA Trial
Disease(s) or condition(s) being studied Haematological Disorders
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Devices
Anticipated trial start date 01/08/2022
Actual trial start date
Anticipated date of last follow up 01/08/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 600
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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 Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group LNG IUS product The LNG IUS product (Avibela®) is a levonorgestrel-releasing intrauterine system consisting of a T-shaped polyethylene frame with a drug reservoir containing 52 mg levonorgestrel, packaged within a sterile inserter. Initially, levonorgestrel is released at a rate of 18.6 mcg/day. The rate decreases progressively to approximately 16.3 mcg/day at 1 year and 14.3 mcg/day at 2 years. The products will be used as explained in the product labels. No dosing alterations will be made. For the LNG IUS, once the product is inserted in the uterus, no dosing actions are required of the participant. This trial will use two contraceptive products that are currently approved by the Kenyan regulatory authorities and available in Kenya: The LNG IUS product (Avibela®) is a levonorgestrel-releasing intrauterine system consisting of a T-shaped polyethylene frame with a drug reservoir containing 52 mg levonorgestrel, packaged within a sterile inserter. Initially, levonorgestrel is released at a rate of 18.6 mcg/day. The rate decreases progressively to approximately 16.3 mcg/day at 1 year and 14.3 mcg/day at 2 years. The products will be used as explained in the product labels. No dosing alterations will be made. For the LNG IUS, once the product is inserted in the uterus, no dosing actions are required of the participant. If the participant tests negative for pregnancy and additionally study staff are reasonably sure the participant is not currently pregnant according to WHO guidelines, the products can be started on the day of enrollment. In some cases, the participant may need to return to the clinic for LNG IUS insertion. Study staff may need to provide back-up contraceptive methods if the participant is 5+ days past the start of her last menses. The World Health Organization’s Family Planning Handbook will be used to help clinicians determine the appropriate starting day of the contraceptive regimens. 300
Control Group Combined oral contraceptive regimen FemiplanTM The combined oral contraceptive regimen (FemiplanTM) is provided in a 28-day blister pack. Each pack contains 21 tablets containing 0.15 mg of levonorgestrel/30 mcg of ethinyl estradiol and 7 tablets containing 75 mg of ferrous fumarate The products will be used as explained in the product labels. No dosing alterations will be made. For the COC regimen, participants will be instructed to take one tablet every day and start the subsequent pack immediately after finishing the previous 28-day regimen. The products will be used as explained in the product labels. No dosing alterations will be made. For the COC regimen, participants will be instructed to take one tablet every day and start the subsequent pack immediately after finishing the previous 28-day regimen. The combined oral contraceptive regimen (FemiplanTM) is provided in a 28-day blister pack. Each pack contains 21 tablets containing 0.15 mg of levonorgestrel/30 mcg of ethinyl estradiol and 7 tablets containing 75 mg of ferrous fumarate.If the participant tests negative for pregnancy and additionally study staff are reasonably sure the participant is not currently pregnant according to WHO guidelines, the products can be started on the day of enrollment. The participant can take the COCs product home and start when appropriate. The World Health Organization’s Family Planning Handbook will be used to help clinicians determine the appropriate starting day of the contraceptive regimens. 300 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Prospective participants must meet the following main criteria: 1. Provide sequential oral and written consents to screen for eligibility and enroll 2. Female, aged 18-50 3. Desire to use contraception or possibly switch methods 4. Initial hemoglobin of < 126 g/L 5. Possession of a cell phone and willingness to be contacted 6. Confirmatory low hemoglobin (minimum of 87 g/L and maximum of 126 g/L) taken 1 to 4 weeks after the initial test 7. Regularly menstruating (at least once every 35 days) 8. At least 6 weeks postpartum 9. Willingness to agree to study procedures 10. Willingness to be randomized to treatment 11. Willingness to use assigned hormonal contraceptive for 18 months An individual who has any of the following will be excluded from participation in this study: 1. Severe anemia (hemoglobin < 86 g/L), based on the second rapid test 2. Currently pregnant based on urine pregnancy test and failure to rule out possible pregnancy according to WHO guidelines (75) 3. Surgically sterilized or had a hysterectomy 4. Participated previously in this study by being randomized to contraceptive 5. Currently using a subdermal contraceptive implant and does not wish to have it removed 6. Currently using an LNG IUS 7. Currently receiving treatment for anemia 8. Any of the following previously diagnosed disorders: hemosiderosis, hemochromatosis, hemolytic anemia 9. Known allergic reactions to oral contraceptives or LNG IUS 10. Currently receiving an investigational (unapproved) drug in another study 11. Any condition (social or medical) which in the opinion of the investigator would make study participation unsafe 12. Intending to become pregnant in the next 18 months 13. Mucopurulent cervicitis 14. Pelvic inflammatory disease 15. Other medical contraindications to treatment, according to WHO Medical Eligibility Criteria (categories 3 or 4)(9) Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 50 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 10/02/2022 KNH UON ERC
Ethics Committee Address
Street address City Postal code Country
Hospital Road Nairobi 196700202 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Mean change in hemoglobin Primary Endpoint: Hemoglobin levels at 6, 12, and 18 months.
Secondary Outcome Serum ferritin changes over time in the randomized arms 6, 12, and 18 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kangemi Health Centre Off Hinga Road, Along Gichanga Road, Nairobi, Kenya Nairobi 00500 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institutes of Health 9000 Rockville Pike Maryland United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor FHI 360 Blackwell Street Durham NC United States of America Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
University of Nairobi Institute of Tropical and Infectious Diseases UNITID Hospital Road Nairobi 00202 Kenya
FHI360 Chancery Bld 2nd Floor, Valley Road, P.O. Box 38835-00623 Nairobi 00623 Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator David Hubacher dhubacher@fhi360.org 9195447040 359 Blackwell Street
City Postal code Country Position/Affiliation
Durham NC United States of America Senior Epidemiologist FHI 360
Role Name Email Phone Street address
Scientific Enquiries Faith Thuita fthuita@uonbi.ac.ke 254204915060 Hospital road
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya Senior Scientist Department of Public and Global Health University of Nairobi
Role Name Email Phone Street address
Public Enquiries Julius Oyugi fthuita@gmail.com 00000000 xxx
City Postal code Country Position/Affiliation
Nairobi xx Kenya UNITID
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the published results of NIH funded research, requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals. Data from this study will be made available to the public per NIH requirements. Informed Consent Form,Statistical Analysis Plan,Study Protocol Two years This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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