Contraceptive Pills for Discontinuing Implants

Overseen By Jeanelle Sheeder, PhD

Age: < 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Etonogestrel implant

Must not be taking: Estrogen birth control

Disqualifiers: Pregnancy desire, Moving plans, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 months

600 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Ethinyl Estradiol / Norgestimate Oral Tablet?

Research shows that Ethinyl Estradiol / Norgestimate is highly effective as a contraceptive, with a very low failure rate (Pearl index of 0.25), and it provides reliable cycle control with minimal side effects like breakthrough bleeding. It also has a favorable impact on metabolic health, such as improving cholesterol levels. ^{1 2 3 4 5}

Is the combination of norgestimate and ethinyl estradiol generally safe for use in humans?

The combination of norgestimate and ethinyl estradiol is generally considered safe for use in humans, with studies showing minimal effects on weight, blood pressure, and metabolism. It has a low incidence of side effects like acne, nausea, or headaches, and is associated with a lower risk of cardiovascular issues compared to other oral contraceptives. ^{1 2 4 6 7}

How does the drug norgestimate/ethinyl estradiol differ from other contraceptive options?

Norgestimate/ethinyl estradiol is unique because it contains a third-generation progestin, norgestimate, which has minimal androgenic effects (less likely to cause male-like side effects) and a lower impact on metabolism, potentially reducing the risk of cardiovascular issues compared to other oral contraceptives. ^{1 3 7 8 9}

What is the purpose of this trial?

To compare rates of etonogestrel implant discontinuation in implant initiators who are given advance provision of combined oral contraceptive pills (COCs) and a bleeding rescue regimen (COCR intervention) to participants given standard counseling (comparator).

Eligibility Criteria

This trial is for young individuals aged 14 to 22.9 who are using the etonogestrel implant as a contraceptive for the first time. It's not suitable for those with estrogen-related contraindications, plans to move away within a year, or a desire to become pregnant in the next year.

Inclusion Criteria

You are between ages of 14 to 22.9 years

Started etonogestrel implant for the first time and have never used the implant before

Exclusion Criteria

There is any contraindication to estrogen containing birth control

Plans to move from the area in next 12 months and is not able to come to the clinic

You plan to become pregnant within the next year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard counseling or the COCR intervention, which includes advance provision of combined oral contraceptive pills and a bleeding rescue regimen

12 months

Regular follow-ups as needed

Follow-up

Participants are monitored for satisfaction with the contraceptive implant and healthcare interactions related to the implant

12 months

3 visits (in-person) at 3, 6, and 12 months

Treatment Details

Interventions

• Ethinyl Estradiol / Norgestimate Oral Tablet

Trial Overview The study tests if giving out combined oral contraceptive pills (COCs) and a bleeding rescue regimen alongside standard counseling reduces premature discontinuation of contraceptive implants compared to just counseling alone.

Participant Groups

Group I: COCR Arm Experimental Treatment 1 Intervention

Participants in the COCR arm will receive three packs of combined oral contraceptive pills (35mcg ethinyl estradiol/norgestimate) and a specific protocol for their use for bothersome bleeding.

Group II: SOC Arm Active Control 1 Intervention

Participants in the SC arm will be offered care according to our standardized protocol, which may include STI testing, reassurance and monitoring, prescription of COCs if desired, or removal.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

Norgestimate/ethinyl estradiol, a new oral contraceptive, shows excellent contraceptive efficacy with a Pearl index of 0.25, indicating a very low failure rate.

This contraceptive has a low impact on carbohydrate and lipid metabolism and does not significantly affect blood coagulation factors, suggesting a potentially lower risk of cardiovascular disease compared to other oral contraceptives, although caution is advised for patients with a history of vascular or thrombotic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Norgestimate: a clinical overview of a new progestin. Bringer, J.[2019]

Both monophasic and triphasic formulations of ethinyl estradiol plus norgestimate have been shown to provide effective contraception, with efficacy comparable to other oral contraceptives, based on numerous clinical studies.

Both formulations demonstrated favorable metabolic effects, such as increasing good cholesterol (HDL) and reducing the LDL/HDL ratio, while showing minimal impact on weight gain, blood pressure, and carbohydrate metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate. Corson, SL.[2019]

In a study involving 19 healthy women, raltegravir did not significantly affect the pharmacokinetics of the estrogen and progestin components of the oral contraceptive norgestimate-ethinyl estradiol, indicating that it can be safely co-administered without requiring dose adjustments.

The study found that co-administration of raltegravir and the contraceptive was well tolerated, with no serious adverse effects reported, suggesting a favorable safety profile for this combination in HIV-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. Anderson, MS., Hanley, WD., Moreau, AR., et al.[2021]

Cyclessa, a new low-dose triphasic contraceptive, demonstrated comparable contraceptive efficacy to Ortho-Novum 7/7/7 while providing significantly better cycle control, including fewer instances of breakthrough bleeding and spotting.

Women using Cyclessa experienced less weight gain and a smaller increase in body mass index compared to those using Ortho-Novum 7/7/7, indicating a favorable safety profile for Cyclessa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, cycle control, and safety of two triphasic oral contraceptives: Cyclessa (desogestrel/ethinyl estradiol) and ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol): a randomized clinical trial. Kaunitz, AM.[2019]

The study analyzed the plasma concentration profiles of three oral contraceptive steroid preparations in Egyptian women, finding that peak plasma concentrations of the estrogen component (EE2) varied significantly among the preparations, with Ovral showing the highest levels.

Despite differences in estrogen content, the pharmacokinetic parameters such as half-life, oral clearance, and volume of distribution were similar across the contraceptives, indicating that the kinetic profiles in healthy Egyptian women are comparable to those in other ethnic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest. el-Raghy, I., Back, DJ., Makeram, M., et al.[2019]

Norgestimate combined with ethinyl estradiol is an effective low-dose oral contraceptive that offers cycle control similar to older formulations while having low androgenic activity, as confirmed by several phase II and III clinical studies.

This combination has been shown to improve lipid profiles by increasing high-density lipoprotein cholesterol and enhancing the low-density/high-density lipoprotein ratio, unlike norgestrel, which has adverse effects on these lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A norgestimate-containing oral contraceptive: review of clinical studies. Kafrissen, ME.[2019]

In a large study of 59,701 women over 342,348 menstrual cycles, the oral contraceptive norgestimate/ethinyl estradiol demonstrated a very low use-efficacy Pearl index of 0.25 pregnancies per 100 woman-years, indicating high effectiveness in preventing pregnancy.

The contraceptive was well-tolerated, with minimal side effects and significant reductions in bleeding intensity for 32% of women, while only 1% experienced amenorrhea and low rates of spotting (4%) and breakthrough bleeding (3%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women. Runnebaum, B., Grunwald, K., Rabe, T.[2022]

The contraceptive patch (Ortho Evra) delivers consistent levels of norelgestromin and ethinyl estradiol, maintaining effective hormone concentrations for up to 10 days, even if a scheduled change is missed for two days.

The patch's pharmacokinetics are stable across different application sites and conditions, such as heat and exercise, and do not interact with tetracycline, ensuring reliable contraceptive efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic overview of Ortho Evra/Evra. Abrams, LS., Skee, D., Natarajan, J., et al.[2019]

In a study of 300 women comparing two oral contraceptives, Brevicon users experienced significantly more intermenstrual bleeding than those using Norinyl 1/35, which could influence their choice to continue using the method.

Despite the differences in side effects, both contraceptives had high discontinuation rates after 11 months, with 68.2% for Norinyl 1/35 and 75.2% for Brevicon, primarily due to menstrual problems and other personal reasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative clinical trial of Norinyl 1/35 versus Brevicon in Rio Clara, Brazil. Albuquerque, LA., Albuquerque, EG., Waszak, CS., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Norgestimate: a clinical overview of a new progestin. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy, cycle control, and safety of two triphasic oral contraceptives: Cyclessa (desogestrel/ethinyl estradiol) and ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol): a randomized clinical trial. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

A norgestimate-containing oral contraceptive: review of clinical studies. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetic overview of Ortho Evra/Evra. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

A comparative clinical trial of Norinyl 1/35 versus Brevicon in Rio Clara, Brazil. [2019]