Patients reported significantly improved health status on the Euro-QoL questionnaire at 12 months postprocedure. At baseline, patients in the Sonography Guided Transcervical Ablation of Uterine Fibroids trial had a mean overall score of 0.72 (N=143). At 12 months (n=133), their mean health utility scores rose 0.17 points to 0.89 (P<.001).
Most patients (97%) at 12 months reported satisfaction with the treatment and the same percentage (97%) would also recommend Sonata to a friend or family member. Specifically, 70.4% of reporting patients (n=135) indicated that they were “very satisfied” with treatment, 17.8% were “moderately satisfied,” 8.9% were “somewhat satisfied,” 2.2% were “somewhat dissatisfied,” and 0.7% were “moderately dissatisfied” at 12 months. Similarly, 81.5% would “definitely recommend” treatment with Sonata, 15.6% would “probably recommend” it, and 3.0% would “probably not recommend” treatment with Sonata at 12 months. No patient indicated dissatisfaction with the treatment or that she would “definitely not recommend” the treatment.
Overall, 98% (144/147) of patients found the transcervical ablation treatment to have been tolerable: 64.6% (n=95) of patients reported the procedure to have been “very tolerable,” 30.6% (n=45) found the procedure “moderately tolerable,” 2.7% (n=4) characterized it as “minimally tolerable,” and 2% (n=3) said it was “intolerable.” Overall mean pain scores (0–10 scale) were 0.2±1.0 (range 0.0–7.0) during the procedure and 2.6±2.8 (range 0.0–10.0) during recovery (reported for the time between procedure completion and discharge and recorded before discharge). Mean procedural pain scores were 0.01±0.1 for procedures under general anesthesia and 0.5±1.3 for procedures under conscious sedation. Mean recovery pain scores were 3.4±2.9 for patients receiving general anesthesia and 1.9±2.4 for those who were treated under conscious sedation. During recovery, 49 patients (33.3%) were managed with nonsteroidal antiinflammatory drugs and 39 patients (26.5%) received narcotics.
On average, patients reported returning to normal daily activities in 2.2±2.2 days, with more than half of the patients returning to normal activity within 1 day of the procedure. Employed patients returned to work in a mean 3.6±2.6 days postprocedure. Patients resumed a normal diet at 0.8±1.3 days, normal sleep at 0.7±1.6 days, and normal urinary and bowel functions at 0.2±0.8 days and 1.4±1.9 days, respectively.
Table 5 summarizes characteristics of ablated leiomyomas. Although patients were excluded for having one or more leiomyomas with diameters greater than 5.0 cm on transvaginal ultrasonogram, intrauterine ultrasonography from the Sonata System was used to provide the data in Table 5 regarding baseline leiomyoma size (for consistency, magnetic resonance measurements by the independent core imaging laboratory at baseline and 12 months were used to provide final comparative data regarding leiomyoma size and volume). On average, leiomyomas received 1.1±0.4 ablations; 64 leiomyomas (14.5%) were treated with two or more ablations. Most (80.8%) ablated leiomyomas ranged from 1 to 4 cm in diameter.
Among the patients whose qualifying leiomyoma(ta) indented the endometrial cavity (types 1, 2, or 2–5), the success rates for achieving 50% or greater reduction in pictorial blood loss assessment chart at 12 months were similar (64.3%, 68.0%, 61.9%; P=.94). For the 25.4% (36/142) of patients included in the analysis of the bleeding reduction coprimary endpoint whose only qualifying leiomyoma was a type 3 myoma, 63.9% (23/36) realized at least a 50% reduction in pictorial blood loss assessment chart score at 12 months. There were no significant differences in study success for either coprimary endpoint regarding the inclusion qualifying leiomyoma type, including patients whose sole qualifying leiomyoma was a type 3 myoma.
At 12 months postprocedure, the mean reduction in total uterine volume was 12.9% (n=133), from 267.3 cm3 at baseline to 232.6 cm3 at 12 months (P<.001). The mean maximal reductions in total and perfused leiomyoma volumes per patient from baseline to 12 months was 62.4% (n=129) and 63.9% (n=128), respectively (P<.001 for both).
There were no occurrences of device-related adverse events, serious or otherwise. There were two procedure-related serious adverse events reported in two patients (1.4%). One involved a deep venous lower extremity thrombus diagnosed 15 days postprocedure, managed as an outpatient without sequelae. The other event involved a patient who had received prophylactic antibiotics at the time of her treatment, but presented with a chief complaint of leukorrhea, pelvic pain, and unconfirmed low-grade fever 28 days postprocedure and was managed with overnight admission and broad-spectrum antibiotics. An independent medical advisory committee concluded that the event was related to leiomyoma sloughing and leukorrhea with no evidence of infection.
Nonserious procedure-related adverse events were reported in 74 patients (50.3%). These included leiomyoma sloughing (30.6%), cramping or pain (7.5%), leukorrhea (6.1%), uncomplicated genitourinary infections (4.8%), nonspecific (constitutional) symptoms (3.4%), expelled leiomyoma (1.4%), flu-like symptoms (1.4%), nausea or vomiting (0.7%), and other nongynecologic events (constipation, sore throat, atelectasis, high blood pressure; 5.4%).
Several studies have advocated for more effective and better tolerated leiomyoma management, because women with uterine leiomyomas often delay or avoid treatment as a result of a lack of acceptable options.2,23 The transcervical route may provide benefits to women with symptomatic leiomyomas compared with open or laparoscopic treatment options, including avoidance of the peritoneal cavity and no requirement for general anesthesia except when necessary on clinical grounds (eg, morbid obesity) or based on anesthesiologist or patient preference.
The leiomyoma ablation system described here could expand access to transcervical leiomyoma treatment beyond the smaller intracavitary or indenting leiomyomas treatable with operative hysteroscopy. In the Sonography Guided Transcervical Ablation of Uterine Fibroids trial, 79% of treated leiomyomas were intramural (types 3 and 4), transmural (type 2–5), and subserosal (types 5 and 6) myomata.
It is noteworthy that the trial included women with heavy menstrual bleeding who had type 3 myomata without leiomyomas that indented the endometrial cavity. At 12 months, these patients had treatment effectiveness similar to that of the overall study population. This suggests a possible association of type 3 leiomyomas with heavy menstrual bleeding. Previous work indicates that type 4 leiomyomas may also be associated with heavy menstrual bleeding.24
There were 24 treating investigators at 22 sites, including academic centers, community hospitals, and several private physician offices. This represents a wide variety of practicing obstetrician–gynecologists, none of whom had prior experience with transcervical leiomyoma ablation. Each investigator received the same training and support, consisting of didactic training followed by procedure simulation with a phantom model of a leiomyoma uterus. The Sonography Guided Transcervical Ablation of Uterine Fibroids trial results suggest that with appropriate training and support, transcervical radiofrequency ablation may be safely and effectively provided by obstetrician–gynecologists.
Limitations of the Sonography Guided Transcervical Ablation of Uterine Fibroids trial include a nonrandomized design, a limit of 5 cm, and the exclusion of patients who desired fertility. Although not randomized, Sonography Guided Transcervical Ablation of Uterine Fibroids is a multicenter interventional trial with prospectively defined endpoints having set objective performance criteria. Well-designed interventional trials can provide compelling evidence for the effectiveness of a treatment.25,26 The Sonography Guided Transcervical Ablation of Uterine Fibroids trial included a robust patient selection process to minimize confounding factors, excluding patients with other etiologies of abnormal uterine bleeding such as anovulation, adenomyosis, and bleeding disorders. Furthermore, the study included a mix of patient-reported outcomes to complement the objective reintervention and bleeding primary endpoints.
Maximum leiomyoma diameter was limited to 5 cm in Sonography Guided Transcervical Ablation of Uterine Fibroids. For purposes of this pivotal trial, leiomyomas were selected that could normally be treated with a single ablation. However, larger leiomyomas could be treated with multiple ablations. In the Sonography Guided Transcervical Ablation of Uterine Fibroids trial, 64 leiomyomas (14.5%) were treated with at least two ablations.
Patients who desired fertility were excluded as a result of ethical reasons because Sonography Guided Transcervical Ablation of Uterine Fibroids was a pivotal safety and effectiveness study. This enriched the eligible population for older patients and minimized the ability to track perinatal and postpartum outcomes. However, the study includes 3-year follow-up of patients and the reporting of any pregnancy outcomes should they occur. In addition, a worldwide clinical registry characterizing the long-term outcomes with transcervical leiomyoma ablation out to 5 years is ongoing (SAGE Global Registry, NCT # 03118037).
The 12-month results from the Sonography Guided Transcervical Ablation of Uterine Fibroids trial compare favorably with other nonextirpative leiomyoma treatments such as uterine artery embolization and laparoscopic radiofrequency ablation. Twelve-month surgical reintervention in the Sonography Guided Transcervical Ablation of Uterine Fibroids trial was 0.7% compared with 10% after uterine artery embolization in the REST trial and 0.7% after a single-arm prospective study of laparoscopic radiofrequency ablation with the Acessa System.27,28 The percentage of patients who met the FDA-required bleeding endpoint at 12 months was higher for the Sonography Guided Transcervical Ablation of Uterine Fibroids trial (64.8%) than that seen in the pivotal trial of the Acessa System (40.2%).28
As demonstrated in the Sonography Guided Transcervical Ablation of Uterine Fibroids trial, transcervical leiomyoma ablation was associated with a significant reduction in leiomyoma symptoms with no device-related adverse events and a low surgical reintervention rate through 12 months. General anesthesia was not required except on clinical or patient and physician grounds. The findings from this study demonstrate the potential of the Sonata System to safely and effectively treat a variety of nonpedunculated leiomyoma types through a uterus-conserving, incisionless approach.
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