RESUMEN
PURPOSE: To evaluate the levonorgestrel-releasing intrauterine system Donasert® (also known as Levosert®) compared with the reference product Mirena® for the alleviation of heavy menstrual bleeding (HMB). MATERIALS AND METHODS: A phase 3 multicentre, non-inferiority, active-controlled study in non-menopausal women with HMB (menstrual blood loss [MBL] ≥ 80 mL) as the primary symptom randomised to either Donasert® or Mirena® and followed for 6 months. MBL was evaluated using a validated, modified version of the Wyatt pictogram. RESULTS: Overall, 312 were randomised (158 to Donasert® and 154 to Mirena®). The mean (standard deviation) absolute change in MBL from baseline to 6 months in the per-protocol population (N = 300) was -130 (71.8) mL and -127 (67.3) mL in the Donasert® and Mirena® groups, respectively; non-inferiority of Donasert® was confirmed (p-value <0.0001). Successful treatment of HMB (MBL <80 mL) and a decrease to ≤50% of baseline MBL was achieved in 139/154 (90.3%) and 126/146 (86.3%) participants in the Donasert® and Mirena® groups, respectively and the between-treatment difference was non-significant. Most adverse events were mild in severity. Only two device expulsions occurred in the study and there were no uterine perforations. CONCLUSIONS: Donasert® has equivalent efficacy and safety during the first 6 months foralleviation of HMB compared to the reference device, Mirena®. TRIAL REGISTRATION NUMBER: 348 (Clinical Trials Registry of the Ministry of Health of the Russian Federation, http://grls.rosminzdrav.ru/default.aspx).
Asunto(s)
Dispositivos Intrauterinos Medicados , Menorragia , Femenino , Humanos , Levonorgestrel/efectos adversos , Menorragia/tratamiento farmacológicoRESUMEN
OBJECTIVE: The aim of the study was to test the hypothesis that in the human uterus, the effectiveness of P2 receptor-mediated contractile responses is up-regulated during pregnancy. STUDY DESIGN: Experiments were performed on myometrial samples obtained from women undergoing caesarean section at 28-30 weeks of pregnancy (3 women, Group 1), 32-34 weeks of pregnancy (6 women, Group 2) and 38-41 weeks of pregnancy (16 women, Group 3). Concentration-response relationships for a non-selective P2 receptor agonist, adenosine 5'-triphosphate (ATP), a selective P2X receptor agonist, alpha,beta-methylene-ATP (alpha,beta-meATP), and a frequency-response relationship for non-adrenergic non-cholinergic (NANC) electrical field stimulation (EFS) were obtained using routine pharmacological organ bath technique. Effects of pyridoxalphosphate azophenyl-2',4'-disulphonic acid (PPADS, 10(-5) M), a P2 receptor antagonist, were also evaluated. Parametric Student's t-test, non-parametric Wilcoxon T-test, Mann-Whitney U-test, two-way analysis of variance (ANOVA) and Krushkal-Wallis tests were used for statistical analysis. RESULTS: ATP (10(-6) to 3 x 10(-4) M), alpha,beta-meATP (10(-7) to 3 x 10(-5) M) and EFS (2-32 Hz) evoked contractions of isolated pregnant uterus in all three groups. Uterus responses to ATP were not correlated with the term of pregnancy while the amplitude of uterine contractions to alpha,beta-meATP and EFS was higher in full term pregnancy than in earlier pregnancy. PPADS antagonized uterus responses to alpha,beta-meATP and EFS, but not to ATP, in all three groups. CONCLUSION: P2X receptor-mediated contractions of human pregnant uterus to alpha,beta-meATP and EFS, but not to ATP, are increased with the progression of pregnancy.