Dataset Information

Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device: Phase 2 Data to 36 Months.

ABSTRACT: OBJECTIVE:To assess in parous and nulliparous women, the efficacy, safety, and tolerability of a new, low-dose copper (175 mm) intrauterine contraceptive with a flexible nitinol frame provided in a preloaded applicator. METHODS:Institutional review boards at 12 U.S. sites approved this commercially funded project. Patients met standard inclusion and exclusion criteria for a copper-based intrauterine device (IUD), generally consistent with the Centers for Disease Control and Prevention's U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. Intrauterine device placement occurred at any day in the eligible patient's menstrual cycle after assuring she was not pregnant. The primary outcome measure assessed efficacy (measured by the Pearl Index) in this 1-year study with a 2-year extension. Secondary outcomes included placement success, ease of placement, safety as measured by adverse events, and tolerability assessed by discontinuation rate and bleeding and spotting patterns. RESULTS:A total of 286 women provided 5,640 cycles evaluable for pregnancy. Patients averaged 27.1 years of age. Nulliparous women represented 60.8% of the patients. Over 36 months of observation, we identified two pregnancies (Pearl Index 0.46 [95% CI 0.06-1.67]) and 10 serious adverse events; none were study-related. Successful placement occurred in 283 participants (99.0%). Median (range) continuation times were 2.7 years (0-3.4). We identified five expulsions (1.8%), zero uterine perforations, and one report of pelvic inflammatory disease. Adverse events prompted 30 women (10.6%) to discontinue early in the first year of use with 23 (8.1%) discontinuing for issues of bleeding, pain, or both. Altogether, 107 (37.8%) completed 36 months of device use. Mean bleeding days per cycle decreased from 7.6 in cycle 1 to 5.2 in cycle 13. CONCLUSION:The novel, low-dose copper and nitinol IUD demonstrated high efficacy and safety in this phase 2 U.S. Food and Drug Administration trial and warrants further expanded study in a phase 3 clinical trial. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT02446821. FUNDING SOURCE:Sebela Pharmaceuticals, Inc.

SUBMITTER: Turok DK

PROVIDER: S-EPMC7098438 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device: Phase 2 Data to 36 Months.

Turok David K DK Nelson Anita L AL Dart Clint C Schreiber Courtney A CA Peters Kevin K Schreifels Mary Jo MJ Katz Bob B

Obstetrics and gynecology 20200401 4

<h4>Objective</h4>To assess in parous and nulliparous women, the efficacy, safety, and tolerability of a new, low-dose copper (175 mm) intrauterine contraceptive with a flexible nitinol frame provided in a preloaded applicator.<h4>Methods</h4>Institutional review boards at 12 U.S. sites approved this commercially funded project. Patients met standard inclusion and exclusion criteria for a copper-based intrauterine device (IUD), generally consistent with the Centers for Disease Control and Preven ...[more]

PMID: 32168217

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Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.

Project description:Background30 years after the introduction of the levonorgestrel-releasing intrauterine device in Europe, several sub-Saharan African countries are seeking to broaden access to this contraceptive method. In this study, we aimed to assess 12-month continuation of the hormonal intrauterine device, copper intrauterine device, and implants, as well as to assess women's experiences and satisfaction using these methods in the private sector in Nigeria and the public sector in Zambia.MethodsWe did a prospective cohort study of long-acting reversible contraceptive users across 40 private sector clinics in Nigeria and 21 public sector clinics in Zambia. Eligible women were aged 18-49 years in Nigeria and 16-49 years in Zambia, had chosen to receive the hormonal intrauterine device, copper intrauterine device, or implant (either a 5-year levonorgestrel-releasing subdermal implant or a 3-year etonogestrel-releasing subdermal implant), and, in Nigeria only, had access to a telephone. Women were interviewed within 100 days of receiving their contraceptive method either via telephone in Nigeria or in person in Zambia, with follow-up surveys at 6 months and 12 months. The primary outcomes were method-specific, 12-month continuation rates-ie, continuation rates of the hormonal intrauterine device, copper intrauterine device, and implant across Nigeria and Zambia. We used Kaplan-Meier methods to estimate the cumulative probabilities of method-specific continuation and a log-rank test to compare contraceptive methods. We analysed self-reported satisfaction and experiences as a secondary outcome.FindingsBetween June 25 and Nov 22, 2018, we enrolled a total of 1542 women (n=860 in Nigeria and n=682 in Zambia) receiving a long-acting reversible contraceptive. In total, 835 women (266 [32%] hormonal intrauterine device users, 274 [33%] copper intrauterine device users, and 295 [35%] implant users) in Nigeria and 367 (140 [38%] hormonal intrauterine device users, 149 [40%] copper intrauterine device users, and 78 [21%] implant users) in Zambia were included in the study analysis. The 12-month cumulative continuation rates were 86·8% (95% CI 82·1-90·4) for the hormonal intrauterine device, 86·9% (82·1-90·4) for the copper intrauterine device, and 85·0% (80·2-88·7) for implants in Nigeria. In Zambia, the 12-month cumulative continuation rates were 94·7% (89·2-97·4) for the hormonal intrauterine device, 89·1% (82·3-93·4) for the copper intrauterine device, and 83·1% (72·2-90·1) for implants. At least 71% of respondents across the timepoints were very satisfied with their method, and at least 55 (79%) of 70 reported having recommended their contraceptive method to someone else. Across the methods, the most commonly self-reported positive aspect of long-acting reversible contraceptive use at 12 months was effectiveness in Nigeria (range 93-94%) and long-lasting duration in Zambia (48-60%). Between 124 (50%) of 248 and 136 (59%) of 230 Nigerian participants and 26 (42%) of 62 and 66 (57%) of 117 Zambian participants reported nothing negative about their contraceptive method.InterpretationOur study showed high continuation rates and satisfaction across long-acting reversible contraceptives, including the hormonal intrauterine device, a method that has been largely underused in sub-Saharan Africa. This finding supports the inclusion of the hormonal intrauterine device as a valuable addition to the mix of contraceptive methods in Nigeria and Zambia.FundingBill & Melinda Gates Foundation.

Dataset Information

Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device: Phase 2 Data to 36 Months.

Publications

Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device: Phase 2 Data to 36 Months.

Similar Datasets

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