0
selected
-
1.
Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids
Stewart EA, Archer DF, Owens CD, Barnhart KT, Bradley LD, Feinberg EC, Gillispie-Bell V, Imudia AN, Liu R, Kim JH, et al
Journal of women's health (2002). 2021
Abstract
Objective: To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Methods: Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Results: Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Conclusion: Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.
-
2.
Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids
Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Feinberg EC, Hurtado SM, Kim J, et al
The New England journal of medicine. 2020;382(4):328-340
Abstract
BACKGROUND Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. CONCLUSIONS Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).
-
3.
Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas
Simon JA, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Dayspring T, Feinberg EC, Gillispie V, Hurtado S, et al
Obstet Gynecol. 2020;135(6):1313-1326
-
-
Free full text
-
Abstract
OBJECTIVE To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas. METHODS Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies. The primary endpoint was the percentage of women with both less than 80 mL menstrual blood loss during final month and a 50% or greater reduction in menstrual blood loss from baseline to final month. Safety evaluations included adverse events and bone mineral density changes. The planned sample size of UF-EXTEND was based on estimated rollover and discontinuation rates in the two preceding studies. RESULTS From September 2016 to March 2019, 433 women were enrolled in UF-EXTEND. Of these women, 218 received up to 12 months of elagolix with add-back therapy; the mean+/-SD age of this group was 42.4+/-5.4 years and 67.3% were black. The percentage of women who met the primary endpoint in this elagolix with add-back group was 87.9% (95% CI [83.4-92.3]). The most frequently reported adverse events with up to 12 months of elagolix plus add-back therapy were hot flush (6.9%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Mean percent decreases in bone mineral density from baseline to extension month 6 were significantly less with elagolix plus add-back therapy than with elagolix alone {between-group difference in lumbar spine: -3.3 (95% CI [-4.1 to -2.5])}. CONCLUSION Up to 12 months of elagolix with add-back therapy provided sustained reduction in menstrual blood loss in women with uterine leiomyomas, with the addition of add-back therapy attenuating the hypoestrogenic effects of elagolix alone. No new or unexpected safety concerns were associated with an additional 6 months of elagolix with addback therapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT02925494. FUNDING SOURCE AbbVie Inc funded this study.
-
4.
A prospective study comparing platelet-rich plasma and LA/corticosteroid in intra-articular injection for the treatment of lumbar facet joint syndrome
Wu J, Zhou J, Liu C, Zhang J, Xiong W, Lv Y, Liu R, Wang R, Du Z, Guizhen Z, et al
Pain Practice : the Official Journal of World Institute of Pain. 2016;17((7):):914-924
Abstract
OBJECTIVES To compare the effectiveness and safety between autologous platelet-rich plasma (PRP) and LA/corticosteroid in intra-articular injection for the treatment of lumbar facet joint syndrome. METHODS Forty-six eligible patients with lumbar facet joint syndrome were randomized into group A (intra-articular injection with PRP) and group B (intra-articular injection with LA/corticosteroid). The following contents were evaluated: pain visual analog scale (VAS) at rest and during flexion, and the Roland-Morris Disability Questionnaire (RMQ), Oswestry Disability Index (ODI), and modified MacNab criteria for pain relief and applications of post-treatment drugs. All outcome assessments were performed immediately after and at 1 week, 1 month, 2 months, 3 months, and 6 months after treatment. RESULTS No significant difference between groups was observed at baseline. Compared with pretreatment, both group A and group B demonstrated statistical improvements in the pain VAS score at rest or during flexion, the RMQ, and the ODI (P < 0.01). And there were significant differences between the 2 groups on the above-mentioned items (P < 0.05). For group B, subjective satisfaction based on the modified MacNab criteria and objective success rate were highest (80% and 85%) after 1 month, but only 50% and 20% after 6 months. However, for group A, they increased over time. In addition, there were no treatment-related complications in either group during follow-up. CONCLUSIONS Both autologous PRP and LA/corticosteroid for intra-articular injection are effective, easy, and safe enough in the treatment of lumbar facet joint syndrome. However, autologous PRP is a superior treatment option for longer duration efficacy. This article is protected by copyright. All rights reserved.
-
5.
Retrograde autologous priming of the cardiopulmonary bypass circuit reduces blood transfusion in small adults: a prospective, randomized trial
Hou X, Yang F, Liu R, Yang J, Zhao Y, Wan C, Ni H, Gong Q, Dong P
European Journal of Anaesthesiology. 2009;26((12):):1061-6.
Abstract
BACKGROUND AND OBJECTIVE Extreme haemodilution occurring with cardiopulmonary bypass imposes a primary risk factor for blood transfusion in small adult cardiac surgical patients. Priming of the cardiopulmonary bypass circuit with patients' own blood [retrograde autologous priming (RAP)] is a technique used to limit haemodilution and reduce transfusion requirements. We designed this study to evaluate the effects of RAP on reducing perioperative blood transfusion in small adults. METHODS One hundred and twenty patients with a body surface area of less than 1. 5 m undergoing first-time, nonemergency cardiac surgery were randomized to either the standard priming group or the RAP group. All patients followed strict transfusion criteria. Homologous transfusion, haematocrit, plasma colloid osmotic pressure and postoperative clinical outcomes were evaluated perioperatively. RESULTS Patient characteristics and operative parameters were equal for patients in both groups. With autologous priming, a mean volume of 614. 8 +/- 138. 8 ml of priming solution was replaced with autologous blood. This allowed a significantly higher haematocrit value during cardiopulmonary bypass (P < 0. 05). Red blood cell transfusion was necessary in 83. 3% of patients of the standard priming group on pump, whereas only 26. 7% of patients of the RAP group required transfusion (P < 0. 01). The overall transfusion rate of the RAP group was significantly less than that in the standard priming group during the hospitalization (90. 0 vs. 50. 0%, P < 0. 01). Amongst patients who received transfusion on pump, the number of homologous units of packed red blood cells was less in the RAP group than that in the standard priming group intraoperatively and perioperatively (0. 94 +/- 0. 32 vs. 1. 48 +/- 0. 68 units, P = 0. 03; 1. 24 +/- 0. 54 vs. 1. 69 +/- 0. 69 units, P = 0. 15). Ten minutes after aortic cross-clamp, colloid osmotic pressure was reduced by 39. 7 +/- 2. 8% in the standard priming group and by 28. 6 +/- 3. 2% in the RAP group (P < 0. 05). Clinical outcomes were similar with respect to pulmonary, renal and hepatic function, length of ICU stay and hospital stay. CONCLUSION RAP resulted in a significant decrease in intraoperative haemodilution and conserved the use of blood. This technique should be considered for patients with a small body surface area (<1. 5 m) undergoing open heart surgery.