489 Pivotal Phase 3 Study of FT218, a Once-Nightly Sodium Oxybate Formulation, in Patients With Narcolepsy: REST-ON Primary Results

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A193-A193
Author(s):  
Clete Kushida ◽  
Colin Shapiro ◽  
Thomas Roth ◽  
Michael Thorpy ◽  
Russell Rosenberg ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Sleep Latency ◽  
Sodium Oxybate ◽  
Mean Difference ◽  
Pivotal Phase ◽  
Double Blind ◽  
Old Patients ◽  
Maintenance Of Wakefulness Test ◽  
To Receive ◽  
Clinical Global Impression Improvement

Abstract Introduction Sodium oxybate (SO) is an effective treatment for patients with narcolepsy; however, currently available SO formulations require twice-nightly dosing. The purpose of this study was to evaluate efficacy and safety of FT218, an investigational once-nightly controlled-release SO formulation, for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy types 1 (NT1) and 2 (NT2). Methods This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Coprimary endpoints were mean sleep latency (minutes) on maintenance of wakefulness test (MWT), Clinical Global Impression-Improvement (CGI-I) of sleepiness, and weekly number of cataplexy attacks (NCAs; NT1 only). Results A total of 212 patients were randomized and received study treatment (FT218, n=107; placebo, n=105). FT218 showed significant (P<0.001) improvement vs placebo in mean sleep latency on MWT for all evaluated doses; LS mean difference (minutes) between FT218 and placebo was 6.13 at 9.0 g (week 13), 6.21 at 7.5 g (week 8), and 4.98 at 6.0 g (week 3). A higher proportion of patients receiving FT218 were much/very much improved on CGI-I vs placebo (72% vs 31.6% at 9.0 g; 62.6% vs 22.8% at 7.5 g; and 40.1% vs 6.1% at 6.0 g; all P<0.001). LS mean difference between FT218 and placebo in mean weekly NCAs was significant (P<0.001) for all doses: −6.65 at 9.0 g, −6.27 at 7.5 g, and −4.83 at 6.0 g. The most common adverse reactions were nausea, vomiting, headache, dizziness, enuresis, and decreased appetite. Conclusion All evaluated doses of FT218 showed significant improvement vs placebo in mean sleep latency on MWT, CGI-I, and weekly NCAs. FT218 was generally well tolerated and the most common adverse events were consistent with known side effects of SO. Support (if any) Avadel Pharmaceuticals.

490 Efficacy of FT218 on Polysomnographic Measures of Sleep Continuity in Patients With Narcolepsy: Results From the REST-ON Trial

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A193-A194
Author(s):  
Yves Dauvilliers ◽  
Michael Thorpy ◽  
Thomas Roth ◽  
Russell Rosenberg ◽  
Bruce Corser ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Sodium Oxybate ◽  
Mean Difference ◽  
Common Symptom ◽  
Nocturnal Sleep ◽  
Double Blind ◽  
Release Formulation ◽  
Double Blind Placebo ◽  
Secondary Endpoints ◽  
To Receive

Abstract Introduction Disturbed nocturnal sleep (DNS) is a common symptom in patients with narcolepsy, characterized by fragmented sleep, including frequent brief nightly awakenings. Sodium oxybate (SO) is an effective treatment for narcolepsy; however, currently available formulations must be taken twice nightly. FT218 is an investigational once-nightly controlled-release formulation of SO. Here, we evaluated the efficacy of FT218 on polysomnographic (PSG) measures of DNS and number of arousals (NAs) in patients with narcolepsy types 1 and 2. Methods This was a randomized, double-blind, placebo-controlled, multicenter study. Patients with narcolepsy aged ≥16 years were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks. Secondary endpoints included PSG measurements of DNS (defined as shifts to wake/N1 from N1, N2, N3, and REM) and NAs (defined per AASM Scoring Manual guidelines [v2.6]). Results Patients receiving FT218 had significant improvements vs placebo in DNS; the LS mean difference between FT218 and placebo was −22.63 for 9.0 g (week 13), −17.70 for 7.5 g (week 8), and −11.00 for 6.0 g (week 3) (all P<0.001). Patients receiving FT218 also had significant reduction in number of NAs vs placebo; the LS mean difference between FT218 and placebo for NAs was −23.68 (P<0.001) for 9.0 g, −19.41 (P<0.001) for 7.5 g, and −11.29 (P=0.021) for 6.0 g. The most common adverse reactions were nausea, dizziness, enuresis, headache, decreased appetite, and vomiting. Conclusion FT218 at all evaluated doses showed significant reduction in DNS and number of NAs vs placebo for all doses of FT218 evaluated. FT218 was generally well tolerated; the most common adverse events were consistent with known SO side effects. FT218 could offer a new once-nightly treatment option for DNS in patients with narcolepsy as demonstrated by PSG measures. Support (if any) Avadel Pharmaceuticals.

492 Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, by Stimulant Use: A Post Hoc Analysis From the REST-ON Study

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A194-A194
Author(s):  
Asim Roy ◽  
Anne Marie Morse ◽  
Jordan Dubow ◽  
David Seiden ◽  
Richard Bogan
Keyword(s):  
Sleep Latency ◽  
Similar Efficacy ◽  
Sodium Oxybate ◽  
Mean Difference ◽  
Double Blind ◽  
Release Formulation ◽  
Old Patients ◽  
Stimulant Use ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Introduction FT218 is an investigational, once-nightly, controlled-release formulation of sodium oxybate for the treatment of narcolepsy. The purpose of this post hoc analysis of the REST-ON study was to evaluate the effect of FT218 on measures of excessive daytime sleepiness (EDS) in patients with narcolepsy with or without stimulant use. Methods This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were stratified by stimulant use and randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Assessments of EDS included mean sleep latency (minutes) on maintenance of wakefulness test (MWT) and Clinical Global Impression-Improvement (CGI-I) in sleepiness. Results A total of 190 patients were included in the modified intent-to-treat population (stimulants: FT218, n=66; placebo, n=53; no stimulants: FT218, n=31, placebo, n=40). Overall, 63% of patients were on concomitant stimulants. Patients receiving FT218 had significant improvement vs placebo in MWT regardless of stimulant use. LS mean difference in mean sleep latency vs placebo for stimulant use was 5.99 for 9.0 g (week 13), 5.51 for 7.5 g (week 8), and 5.35 for 6.0 g (week 3; all P<0.001). For no stimulant use, LS mean difference was 6.28 for 9.0 g (P=0.001), 7.14 for 7.5 g (P<0.001), and 4.19 for 6.0 g (P=0.007). More patients receiving FT218 rated sleepiness as much/very much improved on CGI-I vs placebo (stimulant use: 9.0 g, 80.5% vs 35.3%, odds ratio [OR] 7.55; 7.5 g, 66.3% vs 26.5%, OR 5.44; 6.0 g, 39.8% vs 4.4%, OR 14.27 [all P<0.001]; no stimulant use: 9.0 g, 55.1% vs 27.2%, OR 3.29 [P=0.047]; 7.5 g, 54.5% vs 17.5%, OR 5.64 [P=0.006]; 6.0 g, 40.0% vs 7.7%, OR 8.04 [P=0.003]). FT218 was generally well tolerated. Conclusion FT218 had similar efficacy on EDS at all evaluated doses in narcolepsy patients with or without stimulant use, with improvement over placebo on MWT and CGI-I. FT218 may provide effective treatment for EDS in patients with narcolepsy regardless of stimulant use. Support (if any) Avadel Pharmaceuticals.

491 Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, by Narcolepsy Subtype: A Post Hoc Analysis From the REST-ON Study

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A194-A194
Author(s):  
Asim Roy ◽  
Anne Marie Morse ◽  
Jordan Dubow ◽  
David Seiden ◽  
Richard Bogan
Keyword(s):  
Sleep Latency ◽  
Similar Efficacy ◽  
Sodium Oxybate ◽  
Double Blind ◽  
Release Formulation ◽  
Old Patients ◽  
Post Hoc Analysis ◽  
Intent To Treat ◽  
Subtype A ◽  
Post Hoc

Abstract Introduction FT218 is an investigational, once-nightly, controlled-release formulation of sodium oxybate for the treatment of narcolepsy. The purpose of this post hoc analysis of the REST-ON study was to evaluate the effect of FT218 on measures of excessive daytime sleepiness (EDS) in patients with narcolepsy subtypes 1 (NT1) and 2 (NT2). Methods This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were stratified by narcolepsy subtypes and randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Assessments of EDS included mean sleep latency (minutes) on maintenance of wakefulness test (MWT) and Clinical Global Impression-Improvement (CGI-I) in sleepiness. Results A total of 190 patients were included in the modified intent-to-treat population (NT1: FT218, n=72; placebo, n=73; NT2: FT218, n=21, placebo, n=24). Patients with NT1 or NT2 receiving FT218 had significant improvement in MWT. LS mean difference in mean sleep latency (minutes) vs placebo for NT1 was 5.97 for 9.0 g (week 13), 7.02 for 7.5 g (week 8), and 4.89 for 6.0 g (week 3; all P<0.001), and for NT2, 6.27 for 9.0 g (P=0.020), 4.01 for 7.5 g (P=0.162), and 5.33 for 6.0 g (P=0.020). A higher proportion of NT1 patients receiving FT218 had significant improvement on CGI-I vs placebo (9.0 g: 75.5% vs 35.9%; 7.5 g: 66.9% vs 27.9%; 6.0 g: 39.9% vs 7.8%; all P<0.001). A higher number of NT2 patients receiving FT218 were consistently rated as much/very much improved vs placebo, based on descriptive statistics. FT218 was generally well tolerated. Conclusion FT218 had similar efficacy on EDS at evaluated doses in NT1 and NT2, with improvement in MWT and CGI-I greater than placebo. FT218 may provide effective treatment for EDS in patients with narcolepsy, with or without cataplexy. Support (if any) Avadel Pharmaceuticals.

scholarly journals Once-Nightly Sodium Oxybate (FT218) Demonstrated Improvement of Symptoms in a Phase 3 Randomized Clinical Trial in Patients With Narcolepsy

SLEEP ◽  
2021 ◽  
Author(s):  
Clete A Kushida ◽  
Colin M Shapiro ◽  
Thomas Roth ◽  
Michael J Thorpy ◽  
Bruce C Corser ◽  
...  
Keyword(s):  
Clinical Global Impression ◽  
Epworth Sleepiness Scale ◽  
Clinical Laboratory ◽  
Sleep Latency ◽  
Sodium Oxybate ◽  
Phase 3 ◽  
Maintenance Of Wakefulness Test ◽  
Secondary Endpoints ◽  
Change In Mean ◽  
Clinical Global Impression Improvement

Abstract Study Objectives To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial. Methods Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments. Results In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n=107) or placebo (n=105). For the 3 coprimary endpoints and Epworth Sleepiness Scale, all 3 doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement vs placebo (all P<0.001). For ON-SXB 9 g vs placebo, increase in mean sleep latency was 10.8 vs 4.7 min (LSMD [95% CI], 6.13 [3.52–8.75]), 72.0% vs 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76–11.23]), change in mean weekly number of cataplexy attacks was –11.5 vs –4.9 (LSMD [95% CI], –6.65 [–9.32 to –3.98]), and change in Epworth Sleepiness Scale was –6.5 and –2.7 (LSMD [95% CI], –6.52 [–5.47 to –2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis. Conclusions ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose.

493 Weight Loss With FT218, a Once-Nightly Sodium Oxybate Formulation for the Treatment of Narcolepsy: Post Hoc Analysis From REST-ON

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A194-A195
Author(s):  
Anne Marie Morse ◽  
Asim Roy ◽  
Jordan Dubow ◽  
David Seiden ◽  
Richard Bogan
Keyword(s):  
Weight Loss ◽  
Treatment Group ◽  
Placebo Treatment ◽  
Sodium Oxybate ◽  
Mean Difference ◽  
Analysis Of Covariance ◽  
Double Blind ◽  
Old Patients ◽  
Placebo Treatment Group ◽  
Baseline Weight

Abstract Introduction Patients with narcolepsy are more likely to be obese compared with healthy controls. FT218 is an investigational once-nightly sodium oxybate formulation for the treatment of narcolepsy. Here, we report on changes in weight-related clinical values with FT218 treatment in patients with narcolepsy. Methods This was a randomized, double-blind, placebo-controlled multicenter study in patients with narcolepsy ≥16 years old. Patients were not excluded based on baseline weight or body mass index (BMI). Patients were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Weight and BMI were measured at baseline and study end. LS mean difference in BMI between FT218 and placebo was analyzed using analysis of covariance. Results A total of 107 patients received FT218 and 105 patients received placebo. At baseline, mean (SD) weight was 81.2 (20.8) kg in the FT218 treatment group and 82.1 (22.5) kg in the placebo treatment group. At end of study (week 13), mean (SD) weight was 80.9 (21.9) kg in the FT218 treatment group and 82.25 (21.6) in the placebo treatment group. At week 13, mean (SD) change in weight from baseline was –1.29 (3.6) kg for FT218 and 0.19 (2.6) kg for placebo; 17.5% of patients receiving FT218 vs 3.8% of patients receiving placebo had ≥5% weight loss. At baseline, mean (SD) BMI was 28.1 (7.8) kg/m2 in the FT218 treatment group and 28.2 (6.6) kg/m2 in the placebo treatment group. At study end (week 13), LS mean (SE) change from baseline in BMI was ‒0.51 (0.13) kg/m2 for patients receiving FT218 and 0.08 (0.13) kg/m2 for patients receiving placebo (LS mean difference [95% CI], ‒0.59 [‒0.95 to ‒0.23]; P=0.001). FT218 was generally well tolerated. Conclusion Patients receiving FT218 experienced a significantly greater decrease in weight and BMI vs placebo. These results suggest that treatment with once-nightly FT218 may provide weight-related benefit for patients with narcolepsy and comorbid weight gain. Support (if any) Avadel Pharmaceuticals

485 Efficacy and Safety of Once- and Twice-Nightly Dosing of Lower-Sodium Oxybate in Adults With Idiopathic Hypersomnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A191-A192
Author(s):  
Isabelle Arnulf ◽  
Anne Marie Morse ◽  
Patricia Chandler ◽  
Rupa Parvataneni ◽  
Dan Chen ◽  
...  
Keyword(s):  
Sodium Oxybate ◽  
Mean Difference ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Patient Global Impression ◽  
Idiopathic Hypersomnia ◽  
Secondary Endpoints ◽  
Global Impression Of Change

Abstract Introduction Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder. In a randomized, controlled study of lower-sodium oxybate (LXB; Xywav™) in adults with IH (NCT03533114), significant differences for LXB compared with placebo were observed in Epworth Sleepiness Scale (ESS; primary efficacy endpoint), self-reported Patient Global Impression of Change (PGIc), and IH Severity Scale (IHSS; key secondary endpoints). In this clinical study, investigators were permitted to initiate LXB dosing on a once-nightly or twice-nightly regimen. Methods Eligible participants aged 18–75 years began LXB treatment, administered once or twice nightly during an open-label treatment/titration and optimization period (OLTTOP; 10–14 weeks); dose amount/regimen could be adjusted during this period. Participants next entered a 2-week, open-label, stable-dose period (SDP), then were randomized to placebo or to continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). P values are nominal for this exploratory analysis. Results Of 154 enrolled participants, 40 (26%) initiated LXB treatment on a once-nightly regimen. In the efficacy population (n=115), 27 participants were on a once-nightly regimen during SDP (48.1% of whom initiated treatment once nightly during OLTTOP) and 88 participants were on a twice-nightly regimen during SDP (86.4% of whom initiated treatment twice nightly during OLTTOP). During SDP, median (min, max) LXB total dose was 4.5 (2.5, 6) g/night (once-nightly group) and 7.5 (4.5, 9) g/night (twice-nightly group). ESS scores worsened in participants randomized to placebo vs those continuing LXB in the once-nightly group (n=11 and n=15, respectively; LS mean difference [95% CI]: −4.93 [−7.41, −2.46]; P=0.0004) and twice-nightly group (n=47 and n=41, respectively; LS mean difference [95% CI]: −7.44 [−9.15, −5.72]; P<0.0001). Worsening was also observed in PGIc (once-nightly: 81.8% [placebo] vs 26.7% [LXB]; P=0.0077; twice-nightly: 89.4% [placebo] vs 19.5% [LXB]; P<0.0001) and IHSS score (estimated median difference [95% CI], once-nightly: −9.00 [−16.0, −3.0]; P=0.0028; twice-nightly: −12.00 [−15.0, −8.0]; P<0.0001). Common adverse events included nausea (21.4%), headache (16.2%), anxiety (14.9%), dizziness (11.7%), insomnia (11.7%), and vomiting (10.4%). Conclusion The efficacy and safety of LXB in IH were demonstrated for both once-nightly and twice-nightly regimens. The majority of participants initiated and remained on a twice-nightly regimen. Support (if any) Jazz Pharmaceuticals

Paulinia cupana (Guaraná) purified dry extract (PC-18) for chemotherapy related fatigue in patients solid tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19552-e19552
Author(s):  
Adriana Braz Del Giglio ◽  
Tatiana Goberstein Lerner ◽  
Andrea Thaumaturgo Lera ◽  
Henrique Soares Paiva ◽  
Bruno Carelli ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Controlled Trial ◽  
Mean Difference ◽  
Double Blind ◽  
Dry Extract ◽  
Tumor Types ◽  
Anxiety Depression ◽  
To Receive ◽  
Head Neck

e19552 Background: Paulinia cupana (guaraná) is an amazonic plant with stimulant proprieties which was shown previously to be effective for chemotherapy related fatigue in patients with breast cancer in a randomized double blind placebo controlled trial conducted by our group (J Altern Complement Med. 2011;17(6):505-12). Purpose: Extend our study to patients with different tumor types receiving various regimens of chemotherapy, treated with a purified dry extract of Paulinia cupana (PC-18). Methods: We included patients with solid tumors older than 18 years of age who were scheduled to receive systemic chemotherapy. We excluded patients with fibromyalgia and uncontrolled hypothyroidism, depression, anemia, hypertension or cardiac disease. We evaluated basal fatigue with the BFI questionnaire before chemotherapy, and included only patients who had an increase in their BFI score after one week. PC-18 was given at 50 mg PO bid, starting after one week of chemotherapy. We employed the FACIT-F, BFI, Chalder, HADS and PSQI questionnaires to evaluate fatigue, anxiety, depression and sleep quality at one week and after 4 weeks of chemotherapy. Results: 36 patients with a mean age of 54 years, 61 % female, 28% with breast, 22% colorectal, 8.3% lung , 8.3% head/neck, 5.6% ovarian and 27% of other carcinomas were included. Fatigue scores improved significantly when we compared scores of the BFI (mean difference = 19.39; 95%CI 12.4 – 26.37, p < 0.0001), FACIT-F (mean difference = -11.51; 95%CI -19.25 - -3.76, p = 0.0049) and Chalder (mean difference = 4.571; 95% CI 1.86 – 7.28, p = 0.0018) questionnaires. HADS subscales scores of anxiety (p = 0.025) and depression (p = 0.0095) also improved significantly after 3 weeks of PC-18 therapy. PSQI scores did not change significantly (p = 0.26) after 3 weeks of PC-18 treatment. Conclusions: We conclude that Paulinia cupana (Guaraná) PC-18 extract is active for treatment of chemotherapy related fatigue in patients with a variety of solid tumors and also improves their anxiety and depression scores without worsening the quality of their sleep.

scholarly journals Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease

2020 ◽  
Author(s):  
Aaron Broadwell ◽  
Arkadi Chines ◽  
Peter R Ebeling ◽  
Edward Franek ◽  
Shuang Huang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mineral Density ◽  
Pivotal Phase ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Ckd Stage ◽  
Moderate Chronic Kidney Disease ◽  
To Receive

Abstract Context The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown. Objective This post hoc analysis evaluates the long-term safety and efficacy of denosumab in individuals with mild-to-moderate chronic kidney disease (CKD) (stages 2 and 3) using data from the pivotal phase 3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension (NCT00523341) studies. Participants and Methods Women age 60 to 90 years with a bone mineral density (BMD) T-score of less than –2.5 to greater than –4.0 at the total hip or lumbar spine were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible participants could enroll in the extension to receive denosumab 60 mg subcutaneously every 6 months. Change in estimated glomerular filtration rate (eGFR) from study baseline and annualized rates of fracture and adverse events (AEs) were the main outcome measures. Results Most participants (1259/1969 [64%] long-term arm; 1173/1781 [66%] crossover arm) with baseline CKD stage 2 or 3 remained within the same CKD subgroup at study completion; less than 3% progressed to CKD stage 4. Participants in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of participants reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) both for the long-term (54% vs 52% vs 57% vs 58%) and crossover (43% vs 42% vs 43% vs 68%) arms, except CKD stage 3b subgroup, crossover arm. Conclusion The safety and efficacy of denosumab did not differ among participants with mild to moderate CKD.

scholarly journals Extended Perineural Analgesia After Hip and Knee Replacement When Buprenorphine-Clonidine-Dexamethasone Is Added to Bupivacaine: Preliminary Report from a Randomized Clinical Trial

Pain Medicine ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 2893-2902
Author(s):  
Brian A Williams ◽  
James W Ibinson ◽  
Marsha E Ritter ◽  
Catalin S Ezaru ◽  
Hulimangala R Rakesh ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Knee Replacement ◽  
Mean Difference ◽  
Nerve Blocks ◽  
Double Blind ◽  
Knee Replacement Surgery ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
Time Parameters ◽  
To Receive

Abstract Objective We tested the hypothesis that buprenorphine-clonidine-dexamethasone (BCD) extends perineural analgesia compared with plain bupivacaine (BPV) nerve blocks used for hip and knee replacement surgery. Design Prospective, parallel-arms, randomized, double-blind trial. Setting A single veterans’ hospital. Subjects Seventy-eight veterans scheduled for total hip or knee replacement with plans for spinal as the primary anesthetic. Methods Participants underwent nerve/plexus blocks at L2–L4 and L4–S3 in advance of hip or knee joint replacement surgery. Patients were randomized to receive BPV-BCD or plain BPV in a 4:1 allocation ratio. Patients answered four block duration questions (listed below). Time differences between treatments were analyzed using the t test. Results Significant (P &lt; 0.001) prolongation of the time parameters was reported by patients after the BPV-BCD blocks (N = 62) vs plain BPV (N = 16). The time until start of postoperative pain was 26 vs 11 hours (mean difference = 15 hours, 95% CI = 8 to 21). The time until no pain relief from the blocks was 32 vs 15 hours (mean difference = 17 hours, 95% CI = 10 to 24). The time until the numbness wore off was 37 vs 21 hours (mean difference = 16 hours, 95% CI = 8 to 23). The time until the worst postoperative pain was 39 vs 20 hours (mean difference = 19 hours, 95% CI = 11 to 27). Conclusions BPV-BCD provided 26–39 hours of perineural analgesia in the L2–L4 and L4–S3 nerve distributions after hip/knee replacement surgery, compared with 11–21 hours for plain BPV.

scholarly journals No Difference between Spinal Anesthesia with Hyperbaric Ropivacaine and Intravenous Dexmedetomidine Sedation with and without Intrathecal Fentanyl: A Randomized Noninferiority Trial

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Seung Cheol Lee ◽  
Tae Hyung Kim ◽  
So Ron Choi ◽  
Sang Yoong Park
Keyword(s):  
Spinal Anesthesia ◽  
Sensory Block ◽  
Mean Difference ◽  
Single Shot ◽  
Double Blind ◽  
Noninferiority Trial ◽  
Lower Limb Surgery ◽  
The Mean ◽  
Secondary Outcomes ◽  
To Receive

To enhance the duration of single-shot spinal anesthesia, intrathecal fentanyl and intravenous dexmedetomidine are widely used as adjuvants to local anesthetics. This noninferiority trial evaluated whether hyperbaric ropivacaine alone can produce a noninferior duration of sensory block in comparison to hyperbaric ropivacaine with intrathecal fentanyl in patients under dexmedetomidine sedation. Methods. Fifty patients scheduled for elective lower limb surgery under spinal anesthesia were randomly assigned in a double-blind fashion to receive either hyperbaric ropivacaine 15 mg (Group R) or hyperbaric ropivacaine 15 mg with intrathecal fentanyl 20 μg (Group RF). Intravenous dexmedetomidine (1 μg/kg for 10 min, followed by 0.5 μg/kg/h) was administered in both groups. The primary outcome of this study was the time to two-dermatomal regression of sensory block. The noninferiority margin for the mean difference was −10 min. Characteristics of the block, intraoperative and postoperative side effects, postoperative pain score, and analgesic consumption were assessed as secondary outcomes. Results. There was no difference in the two-dermatomal regressions of sensory block between the two groups (Group R 70.4 ± 10.2 min, Group RF 71.2 ± 12.4 min, p  = 0.804) with a mean difference of 0.8 min (−7.2 to 5.6, 95% confidence interval). Thus, the noninferiority of hyperbaric ropivacaine alone was established. There were no significant differences in the secondary outcomes between the two groups. Conclusions. Under intravenous dexmedetomidine sedation, the duration of spinal anesthesia with hyperbaric ropivacaine alone was noninferior to that of hyperbaric ropivacaine with intrathecal fentanyl. This suggests that addition of intrathecal fentanyl to hyperbaric ropivacaine may not be necessary in patients receiving intravenous dexmedetomidine.

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