CCTN - CONTRACEPTIVE CLINICAL TRIALS NETWORK - EVALUATION REVERSIBLE CONTRACEPTIVE

The Contraceptive Discovery and Development Branch (CDDB) under the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is committed to develop new methods that are long-acting reversible contraceptives (LARCs) that can provide safe and effective contraception for women who may have risk factors against some contraceptive products as well as reduce the risk of venous thromboembolism (VIE). The copper intrauterine devices (IUDs) are examples of intrauterine systems that provide long-acting contraceptive benefits without exogenous hormones or disruption of the regular menstrual cycle. LARC methods include IUDs, implants, or long acting vaginal rings. LARC methods are more effective than daily, weekly or monthly products because they are less prone to user error. IUDs and implants have an effectiveness rate that is in the top tier for typical use (>99% effective). Development of new LARC methods is a high priority for the CDDB. Of the currently approved LARC methods, copper-containing IUDs are the only highly effective reversible methods that do not involve administration of hormones and do not cause irregular or unscheduled bleeding patterns in women. These properties make a copper IUD an ideal method for women who do not wish to take or cannot take hormonal contraceptive methods. Products containing the synthetic estrogen and ethinyl estradiol have been associated with a dose-dependent increase in VIE. Copper IUDs do not increase the risk of VTE and would therefore be suitable for use by women who have an increased risk ofVTE, such as obese women, pregnant women and women with Leiden Factor V. Currently there is one copper IUD, Copper T380 (Paragard®), available in the US. This IUD is associated with pain on insertion and with a high incidence cramping and heavy bleeding during subsequent months of use. The number one reason for discontinuation of the method is the incidence ofheavy bleeding and cramping associated with the device. Preliminary data from some studies indicate that newer copper IUDs may be associated with a lower incidence of heavy bleeding and/or cramping and some devices may have less pain with insertion. It is unclear if any of the newer devices could have a lower incidence of expulsion in some populations of women. In order to evaluate if new LARC products could be effective for contraception, and have a lower incidence of side effects that might lead to discontinuation, a prospective randomized controlled clinical trial will be conducted in the NICHD Contraceptive Clinical Trials Network (CCTN). The products proposed to be tested are LARCs as described above. These products will be compared to the currently available LARC methods. The proposed study will be conducted in women of reproductive age in order to evaluate contraceptive efficacy, pain of insertion, bleeding patterns, associate cramping, expulsion rates as well as other safety and side effects of the long-acting reversible contraceptives (LARCs).