By Rebecca Bowers

EXECUTIVE SUMMARY

Patient enrollment has begun in the United States for Phase III trials of a new copper intrauterine device (IUD) with a flexible frame. The IUD’s design accommodates the uterine contour and features a lower total load of copper to improve comfort and reduce bleeding. The frame is made of nitinol, an alloy of nickel and titanium.

  • The Phase III trial is designed as a prospective, multi-center, single-arm, open-label clinical study to three years, with possible extension up to five years.
  • Women in the United States who prefer to use a nonhormonal, long-acting, reversible contraceptive currently have a single option — the copper T380A IUD.

Women in the United States who prefer to use a nonhormonal, long-acting, reversible contraceptive (LARC) currently have a single option the copper T380A intrauterine device (IUD). The copper IUD is a popular choice for many women, with global statistics indicating the device is used by more than 200 million women.1

Patient enrollment has begun in the United States for Phase III trials of the VeraCept IUD, a new copper IUD with a flexible frame. This IUD’s design accommodates the uterine contour and features a lower total load of copper to improve comfort and reduce bleeding. The frame is made of nitinol, an alloy of nickel and titanium.

During insertion, the device is placed just inside the internal cervical os and bilaterally at the tubal ostea. The device measures 30 mm by 32 mm. By comparison, the copper T380 measures 32 mm horizontally and 36 mm vertically.2 The VeraCept has 175 mm2 of copper surface area, which is less than the 380 mm2 surface area of the T380A.

The T380A IUD has a typical use failure rate of 0.8 per 100 women.3 By comparison, the two 52-mg levonorgestrel IUDs have typical use failure rates of 0.1 per 100 women.3

A Phase II trial of the VeraCept device involved 286 women at 12 U.S. centers with 4,263 cycles evaluated for pregnancy. About 60% of the women enrolled were nulliparous. Over 24 months of observation, one pregnancy occurred (Pearl Index 0.30; 95% confidence interval, 0.01-1.70). Placement was successful in 283 women, with a reported mean pain score of 1.44 at insertion. At one year, 177 women elected to continue using the device, with 135 of them (76.2%) continuing use until 24 months. About 15% of women stopped using the device early because of adverse events.4

The current Phase III trial is designed as a prospective, multi-center, single-arm, open-label clinical study to three years, with possible extension up to five years. Women who are post-menarcheal and pre-menopausal up to age 45, who are at risk for pregnancy, and who desire a long-term intrauterine contraceptive for birth control are eligible for the study. The study’s estimated completion date is in 2024.

Review the Current Option

The copper-containing IUD that is currently available was introduced in the United States in 1988. It is an extremely effective form of birth control, with a failure rate of 0.3% to 0.6%.5 The device features a copper surface area of 380 mm2. Each arm of the device has a solid copper sleeve, with copper wire wrapped around the 36-mm vertical stem. A monofilament polyethylene thread is tied through the base to create two 10.5-cm long, white tailstrings for device detection and removal. The device is designed for use by women whose uterine cavities sound to a depth of 6-9 cm.5

Most medical conditions do not create restrictions for copper IUD use, according to the U.S. Medical Eligibility Criteria for Contraceptive Use.6 Because the copper IUD is a nonhormonal contraception method, it can be used by women with medical contraindications to progestogens, such as women with hepatic dysfunction progestin-sensitive tumors, as well as those who prefer to avoid using synthetic hormones.5 The category 4 conditions (conditions that represent an unacceptable health risk if the method is used) for IUD placement include pregnancy, cervical/uterine/pelvic infection or cancer (cervical or endometrial), distorted uterine cavities, and undiagnosed abnormal uterine bleeding.5

Many women choose to continue using the copper IUD. In the CHOICE study of contraceptive methods, researchers found that among copper IUD users, 23%, 35.8%, and 44.1% had stopped using the device at 24 months, 48 months, and 60 months, respectively.7 In international studies, one-quarter to one-third of women used the device for 10 years.8 Although the copper IUD is approved by the Food and Drug Administration for up to 10 years of use, many family planning organizations routinely allow use of the device for 12 years before recommending removal. Results from a small study indicate that the copper IUD could provide contraception effectively for 20 years.9

The copper IUD is the most effective method of emergency contraception, with a 0.1% risk of pregnancy. It provides ongoing contraception, regardless of the point during the menstrual cycle when it is inserted or the number of days since unprotected intercourse.6

Dealing With Side Effects

Typically, copper IUDs do not cause a change in menstrual frequency, but currently available products can increase menstrual flow and cramping abdominal pain. Research indicates about 10% to 13% of users will have the IUD removed because of bleeding during the first year of use.10 With the potential for increased bleeding and cramping associated with copper IUDs, developers of the new IUD hope it will offer improvement.

In a randomized, subject-blinded comparison of the VeraCept IUD and the copper T380, data indicate use of the VeraCept device resulted in less pain at insertion, fewer device expulsions, and increased total continuation compared to the T380, with a similar level of contraceptive efficacy.11

How can clinicians help patients cope with bleeding? Randomized controlled trials indicate that the use of nonsteroidal anti-inflammatory drugs reduces heavy or prolonged menstrual bleeding from copper IUDs. Antifibrinolytic agents also may reduce bleeding.12,13 Treatment can ease distress and improve continuation rates, as well as prevent iron deficiency in women who use IUDs. 

REFERENCES

  1. United Nations, Department of Economic and Social Affairs, Population Division. Trends in Contraceptive Use Worldwide 2015. Available at: https://bit.ly/21QJ8Zx. Accessed March 20, 2019.
  2. Turok DK, Gawron LM, Lawson S. New developments in long-acting reversible contraception: The promise of intrauterine devices and implants to improve family planning services. Fertil Steril 2016;106:1273-1281.
  3. Dean G, Schwarz EB. Intrauterine devices. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 21st revised edition. New York: Ayer Company Publishers; 2018.
  4. Turok D, Nelson A. Phase 2 efficacy, safety and tolerability results of the veracept low-dose copper intrauterine contraceptive: 24-month data. Contraception 2018;98:355.
  5. Nelson AL, Massoudi N. New developments in intrauterine device use: Focus on the US. Open Access J Contracept 2016;7:127-141.
  6. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016;65:1-103.
  7. Diedrich JT, Madden T, Zhao Q, Peipert JF. Long-term utilization and continuation of intrauterine devices. Am J Obstet Gynecol 2015;213:822.
  8. Kaneshiro B, Aeby T. Long-term safety, efficacy, and patient acceptability of the intrauterine Copper T-380A contraceptive device. Int J Womens Health 2010;2:211-220.
  9. Sivin I. Utility and drawbacks of continuous use of a copper T IUD for 20 years. Contraception 2007;75(Suppl6):S70-S75.
  10. Hubacher D, Reyes V, Lillo S, et al. Preventing copper intrauterine device removals due to side effects among first-time users: Randomized trial to study the effect of prophylactic ibuprofen. Hum Reprod 2006;21:1467-1472.
  11. Reeves MF, Katz BH, Canela JM, et al. A randomized comparison of a novel nitinol-frame low-dose-copper intrauterine contraceptive and a copper T380S intrauterine contraceptive. Contraception 2017;95:544-548.
  12. Grimes DA, Hubacher D, Lopez LM, Schulz KF. Non-steroidal anti-inflammatory drugs for heavy bleeding or pain associated with intrauterine-device use. Cochrane Database Syst Rev 2006;(4):CD006034.
  13. Godfrey EM, Folger SG, Jeng G, et al. Treatment of bleeding irregularities in women with copper-containing IUDs: A systematic review. Contraception 2013;87:549-566.