Contraceptive Implant for Sickle Cell Disease

(SCD CURE Trial)

Overseen By Arden McAllister, MPH

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Hormonal contraception

Disqualifiers: SC disease, Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 10 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a contraceptive implant called Nexplanon to determine its effects on women with sickle cell disease (SCD). Researchers aim to discover if the implant can reduce pain episodes known as vaso-occlusive crises, improve quality of life, and affect blood health. Women with SCD who frequently experience pain episodes and are willing to stop using other hormonal birth control might be suitable for this study. Participants will either receive the Nexplanon implant or continue with their usual care for comparison. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective Nexplanon can benefit more patients with SCD.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop any hormonal contraception and have a 1-month washout period before enrolling. Other medications for sickle cell disease should not have changed in the past 3 months.

Will I have to stop taking my current medications?

The trial requires you to stop any hormonal contraception and have a 1-month period without it before joining. However, it does not specify if you need to stop other medications.

What is the safety track record for Nexplanon?

Research has shown that the contraceptive implant, Nexplanon, is generally safe for women with sickle cell disease (SCD). Studies have found no major changes in lab tests during the first year of use, indicating good tolerance. Some women have noticed changes in their bleeding patterns, but these changes are not severe. Additionally, the implant may reduce the intensity and frequency of pain crises in women with SCD. Overall, Nexplanon is considered a safe and effective option for managing symptoms in these patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using Nexplanon, a contraceptive implant, for individuals with sickle cell disease because it offers a unique approach to managing this condition. Unlike standard treatments like hydroxyurea or blood transfusions, which primarily target the symptoms or complications of sickle cell disease, Nexplanon provides a long-term, reversible contraception option that could be safer and more convenient for women with this condition. Its delivery method, a small rod implanted under the skin, offers consistent hormone release over three years, reducing the burden of daily medication. This novel application could simplify the management of sickle cell disease for women and improve their quality of life.

What is the effectiveness track record for Nexplanon in women with sickle cell disease?

Research has shown that the contraceptive implant Nexplanon, which releases etonogestrel, can benefit women with sickle cell disease. Studies have found that this implant reduces the frequency and severity of pain crises, common in individuals with this condition. Specifically, earlier research demonstrated that women experienced fewer painful episodes. In this trial, participants will receive Nexplanon to evaluate its impact on sickle cell disease. Already approved for birth control, Nexplanon shows promise in improving the quality of life for sickle cell patients. Overall, Nexplanon appears to provide effective pain relief for women with sickle cell disease. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for women aged 18-45 with Sickle Cell Disease (specifically SS or SB0 types) who experience at least one pain episode a month. Participants must not be on hormonal contraception, pregnant, breastfeeding, or planning to become pregnant soon. They should have stable sickle cell medication use and no contraindications to the Nexplanon implant.

Inclusion Criteria

Willing to comply with study procedures

I am a woman aged between 18 and 45.

I have been diagnosed with sickle cell disease.

Exclusion Criteria

I have sickle cell disease.

Contraindications to use of Nexplanon device as per clinical standards

Currently pregnant or pregnant within the last month or seeking to become pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

No Hormonal Intervention

Participants are observed for 3 months without hormonal contraceptive intervention, using either abstinence, barrier methods, or other non-hormonal contraceptive methods

3 months

Progestin Implant

Participants receive the progestin implant and are observed for its impact on vaso-occlusive crises, quality of life, and hematologic parameters

6 months

Follow-up

Participants are monitored for safety and effectiveness after the treatment phases

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nexplanon

Trial Overview The study tests the Nexplanon contraceptive implant's effects on women with Sickle Cell Disease. It aims to see if it changes the number of pain crises they have, affects their quality of life, or alters blood parameters related to their condition.

How Is the Trial Designed?

Group I: Nexplanon Active Control 1 Intervention

Group II: Baseline Active Control 1 Intervention

Nexplanon is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Nexplanon for:

• Birth control

Approved in European Union as Nexplanon for:

• Birth control

Approved in Canada as Nexplanon for:

• Birth control

Approved in United Kingdom as Nexplanon for:

• Birth control

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a study involving 24 healthy young females, the bioavailability of etonogestrel from two different oral contraceptive formulations (Cerazette and Liseta) was found to be similar, indicating that both are effective in delivering the hormone, with geometric mean bioavailability values of 0.79 and 0.82, respectively.

The pharmacokinetics of etonogestrel showed that after daily dosing of Cerazette for 7 days, a steady state was reached by day four, with an elimination half-life of approximately 30 hours, suggesting consistent hormone levels in the body with regular use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability and bioequivalence of etonogestrel from two oral formulations of desogestrel: Cerazette and Liseta. Timmer, CJ., Srivastava, N., Dieben, TO., et al.[2022]

A case study highlighted that improper insertion of the etonogestrel contraceptive implant (Implanon®) can lead to forearm pain and hypoesthesia due to contact with the medial cutaneous nerve, emphasizing the need for correct insertion techniques.

The newer Nexplanon® implant features a redesigned applicator aimed at improving insertion accuracy and reducing the risk of nerve injury during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropathy associated with etonogestrel implant insertion. Brown, M., Britton, J.[2022]

In a study involving 34 women, ultrasound was able to accurately locate non-palpable Implanon contraceptive implants in 33 cases, demonstrating its effectiveness as a localization tool.

Out of 24 patients referred for removal, 20 had their implants successfully extracted using ultrasound guidance, indicating that this method is not only accurate but also safe for guiding removal procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound localisation and removal of non-palpable Implanon implants. James, P., Trenery, J.[2022]

In a study of 65 women comparing the NuvaRing (RING) to a low-dose oral contraceptive (PILL) over five cycles, the RING showed a lesser impact on carbohydrate metabolism, indicating it may be a safer option for insulin sensitivity.

The RING also resulted in a greater reduction of free androgen and dehydroepiandrosterone sulfate levels compared to the PILL, suggesting potential benefits in managing hormonal profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive. Elkind-Hirsch, KE., Darensbourg, C., Ogden, B., et al.[2007]

The new next-generation applicator (NGA) for the radiopaque etonogestrel (ENG) implant was well-received by both experienced and inexperienced clinicians, with nearly all expressing satisfaction after multiple insertions.

The radiopaque implant was successfully visible on X-ray imaging, and while most insertions were easy, adherence to proper insertion instructions was crucial to avoid errors, as three incorrect insertions occurred due to noncompliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinician satisfaction and insertion characteristics of a new applicator to insert radiopaque Implanon: an open-label, noncontrolled, multicenter trial. Mansour, D., Mommers, E., Teede, H., et al.[2022]

The study assessed the pharmacokinetics of etonogestrel and ethinylestradiol from the NuvaRing in 16 healthy women, finding that maximum serum levels were reached in about one week after insertion.

While the NuvaRing provided similar systemic exposure to etonogestrel compared to the oral contraceptive, it resulted in approximately 50% lower exposure to ethinylestradiol, suggesting a potentially different safety and efficacy profile for the vaginal ring compared to the oral contraceptive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Timmer, CJ., Mulders, TM.[2018]

Over a 10-year period, 5433 adverse effects (AEs) were reported for the etonogestrel contraceptive implant, with only 7% classified as serious, indicating that while AEs are common, they are mostly not severe.

The introduction of Nexplanon® has significantly reduced complications related to insertion and migration of the implant, highlighting improvements in safety and efficacy compared to its predecessor, Implanon®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety profile of etonogestrel contraceptive implant (Nexplanon® and Implanon®) reported in France]. Simon, C., Agier, MS., Béné, J., et al.[2017]

In a study of 152 postpartum patients, early insertion of the Implanon contraceptive implant did not significantly affect the duration of lochia, with both treatment and control groups experiencing similar median durations of around 25 days.

Out of the women who had Implanon inserted, 17.7% experienced prolonged or intermittent vaginal bleeding beyond 50 days postpartum, leading to their implant removal, indicating a potential side effect of the contraceptive method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective cohort study of early postpartum etonogestrel implant (Implanon®) use and its effect on duration of lochia. Dobromilsky, KC., Allen, PL., Raymond, SH., et al.[2019]

A new ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to accurately measure etonogestrel (ENG) levels in serum, which is crucial for understanding its pharmacokinetics in contraceptive use.

The method demonstrated high sensitivity with detection limits as low as 25 pg/mL and was successfully applied to assess ENG levels in patients, helping to determine the efficacy of contraceptive implants and the need for removal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A UPLC-MS/MS method for therapeutic drug monitoring of etonogestrel. Thomas, T., Petrie, K., Shim, J., et al.[2021]

Nexplanon® is a long-acting contraceptive implant that is generally considered safe, but it can occasionally cause moderate to severe adverse reactions.

A specific case of delayed-type hypersensitivity reaction to Nexplanon® was reported, which resolved after the implant was removed, highlighting the importance of monitoring for potential allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed-type hypersensitivity reaction against Nexplanon®. Serati, M., Bogani, G., Kumar, S., et al.[2014]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0027968424002074

Impact of Etonogestrel-releasing contraceptive implant use ... Etonogestrel-releasing contraceptive implants were associated with a reduction in the intensity and frequency of pain crises in women with sickle cell disease.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39428270/

Impact of Etonogestrel-releasing contraceptive implant use ... Conclusions: Etonogestrel-releasing contraceptive implants were associated with a reduction in the intensity and frequency of pain crises in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02594462

Contraception in Women With Sickle Cell Disease The objective of this study is to evaluate the clinical effect through safety of etonogestrel-releasing contraceptive implant in women with sickle cell anemia ...

4. ajmc.com ajmc.com/view/etonogestrel-contraceptive-implants-reduce-pain-crises-in-women-with-sickle-cell-disease

Etonogestrel Contraceptive Implants Reduce Pain Crises ... Etonogestrel-releasing contraceptive implants in women with sickle cell disease significantly reduced pain intensity and frequency of pain ...

5. trial.medpath.com trial.medpath.com/clinical-trial/f93c9af29e30d52e/effects-contraceptive-implant-women-sickle-cell-disease

Effects of the Contraceptive Implant in Women With Sickle Cell ... This study aims to measure the acceptability and impact of the progestin implant on frequency of vaso-occlusive crises, quality of life, and hematologic ...

6. contraceptionjournal.org contraceptionjournal.org/article/S0010-7824(25)00466-4/abstract

Safety of hormonal contraception among women with ... Evidence remains limited for adverse health outcomes, especially thrombosis, with HC use among women with SCD. The certainty of evidence was low ...