scholarly journals Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy

SLEEP ◽  
2020 ◽  
Author(s):  
Richard K Bogan ◽  
Michael J Thorpy ◽  
Yves Dauvilliers ◽  
Markku Partinen ◽  
Rafael Del Rio Villegas ◽  
...  
Keyword(s):  
Placebo Group ◽  
Group Versus ◽  
Sodium Oxybate ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Titration Period ◽  
Secondary Efficacy Endpoint ◽  
Optimized Treatment

Abstract Study Objectives Evaluate efficacy and safety of lower-sodium oxybate (LXB), a novel oxybate medication with 92% less sodium than sodium oxybate (SXB). Methods Adults aged 18–70 years with narcolepsy with cataplexy were eligible. The study included a ≤30-day screening period; a 12-week, open-label, optimized treatment and titration period to transition to LXB from previous medications for the treatment of cataplexy; a 2-week stable-dose period (SDP); a 2-week, double-blind, randomized withdrawal period (DBRWP); and a 2-week safety follow-up. During DBRWP, participants were randomized 1:1 to placebo or to continue LXB treatment. Results Efficacy was assessed in 134 participants who received randomized treatment, and safety was assessed in all enrolled participants (N = 201). Statistically significant worsening of symptoms was observed in participants randomized to placebo, with median (first quartile [Q1], third quartile [Q3]) change in weekly number of cataplexy attacks from SDP to DBRWP (primary efficacy endpoint) in the placebo group of 2.35 (0.00, 11.61) versus 0.00 (−0.49, 1.75) in the LXB group (p < 0.0001; mean [standard deviation, SD] change: 11.46 [24.751] vs 0.12 [5.772]), and median (Q1, Q3) change in Epworth Sleepiness Scale score (key secondary efficacy endpoint) of 2.0 (0.0, 5.0) in the placebo group versus 0.0 (−1.0, 1.0) in the LXB group (p < 0.0001; mean [SD] change: 3.0 [4.68] vs 0.0 [2.90]). The most common treatment-emergent adverse events with LXB were headache (20.4%), nausea (12.9%), and dizziness (10.4%). Conclusions Efficacy of LXB for the treatment of cataplexy and excessive daytime sleepiness was demonstrated. The safety profile of LXB was consistent with SXB. Clinical trial registration NCT03030599.

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

scholarly journals 0753 Cataplexy-Free Days in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of JZP-258 in Adults With Narcolepsy With Cataplexy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A286-A286
Author(s):  
Y Dauvilliers ◽  
N Foldvary-Schaefer ◽  
R K Bogan ◽  
K Šonka ◽  
J Profant ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Open Label ◽  
Double Blind ◽  
Stable Dose ◽  
Titration Period ◽  
Product Candidate ◽  
Treatment Naïve ◽  
Optimized Treatment ◽  
To Receive ◽  
Efficacy Population

Abstract Introduction Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate with 92% less sodium. This analysis evaluated cataplexy-free days/week, as a measure of treatment impact, in a placebo-controlled randomized withdrawal study of JZP-258 treatment in patients with narcolepsy. Methods Treatment for cataplexy at study entry included 1) SXB (SXB-only); 2) SXB plus other anticataplectics (SXB+other); 3) anticataplectics other than SXB (other anticataplectics); or 4) cataplexy treatment-naive (anticataplectic-naive). Participants (aged 18-70 years with narcolepsy with cataplexy) began JZP-258 treatment during a 12-week, open-label, optimized treatment and titration period (OLOTTP), followed by a 2-week stable-dose period (SDP). Participants were randomized to receive placebo or continue JZP-258 treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). Results Of 201 enrolled participants, 134 comprised the efficacy population (placebo, n=65; JZP-258, n=69). Median (Q1, Q3) cataplexy-free days/week at first week of OLOTTP (while initiating JZP-258) by prior treatment were SXB-only, 5.8 (2.0, 7.0); SXB+other, 6.4 (5.0, 7.0); other anticataplectics, 4.0 (1.8, 6.0); anticataplectic-naive, 3.5 (0, 5.8). At end of SDP (on stable dose of JZP-258), median (Q1, Q3) cataplexy-free days/week were 6.0 (3.5, 7.0), 6.1 (1.4, 7.0), 6.0 (2.6, 7.0), and 6.2 (4.0, 7.0), respectively. Prior to randomization, there was no difference in median cataplexy-free days/week between participants to be randomized to placebo (6.0 [3.5, 7.0]) or JZP-258 treatment (6.0 [3.0, 7.0]); during DBRWP, median cataplexy-free days/week decreased in participants randomized to placebo (3.5 [0, 5.83]) but remained similar in participants randomized to continue JZP-258 treatment (5.6 [2.8, 7.0]). The overall safety profile of JZP-258 was similar to SXB. Conclusion Number of cataplexy-free days/week increased with JZP-258 treatment in participants previously naive to oxybate. Number of cataplexy-free days/week decreased during placebo exposure in participants randomized to placebo. Support Jazz Pharmaceuticals

scholarly journals Prevention of acute respiratory viral infections and influenza in children during the peaks of seasonal morbidity: the results of the international double-blind placebo-controlled randomized clinical trial

2020 ◽  
Vol 65 (3) ◽  
pp. 109-120
Author(s):  
N. A. Geppe ◽  
A. V. Gorelov ◽  
O. V. Shamsheva ◽  
I. G. Sitnikov ◽  
E. P. Sitnikova ◽  
...  
Keyword(s):  
Placebo Group ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Group Versus ◽  
Study Drug ◽  
Preventive Therapy ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Respiratory Viral Infections

The authors conducted an international multicenter double-blind, placebo-controlled clinical study to obtain additional data on the efficacy and safety of a 12-week course of Anaferon for children for the prevention of acute respiratory viral infections (ARVI), including influenza, in children during the rise in seasonal morbidity (RCT of the Ministry of Health of the Russian Federation: №356 dated June 29, 2017; ClinicalTrials.gov Identifier: NCT03301155).Materials and methods. The study involved 1,036 children (1 month – 6 years 11 months 29 days) during two epidemiological seasons. The patients were divided into 2 groups: 528 patients received Anaferon for children 1 tablet a day for 12 weeks, 508 patients received placebo according to Anaferon for children scheme. The primary end point was the duration of the period from the first dose of the drug until manifestation of ARVI/influenza. Additional end points were percentage of children not falling with ARVI/influenza during 4-, 8- and 12-week course of preventive therapy; percentage of children with respiratory or ear-nose-throat bacterial infections requiring antibiotics within 12 week; percentage of children hospitalized with ARVI/influenza or their complications within 12 week. To assess safety, the authors analyzed the presence and nature of the adverse events (AEs), their severity, connection with the medication, outcome. The authors used the following statistical methods: calculation of hazard ratio, median time to the manifestation of symptoms of ARVI / influenza, 95% confidence intervals.Results. The Intention-to-treat (ITT) and Per Protocol [РР] analysis included the data of 1,021 [975] patients: 520 [494] – Anaferon for children group and 501 [481] –Placebo group. The average duration of the period from the first dose of the drug to the development of ARVI/influenza symptoms obtained as a result of the analysis of the statistical model was 428.8 [434.1] days for Anaferon for children group, that is 1.5 times higher than in Placebo group (275.8 [274.9] days; p=0.001 [p=0.0009]). The percentage of children without ARVI/influenza was 99.2% [99.2%] in Anaferon for children group (versus 90.2% [90.0%] in Placebo group; p=0.0003 [p=0.0003]) within 4 weeks, 92.7% [92.3%] (versus 82.8% [82.7%]; p=0.0003 [p=0.0003]) within 8 weeks, and 81.5% [81.8%] (versus 73.4% [73.4%], respectively; p=0.0021 [p=0.0021]). None of the patients was hospitalized for ARVI/influenza or complications. The frequency of AEs in Anaferon for children and Placebo groups had no differ. No one AE definitely related to the study drug was registered.Conclusion. The results confirm the efficacy and safety of a 12-week course of Anaferon for children to prevent ARVI and influenza during seasonal rise of morbidity in children.

486 Timing and Duration of Adverse Events in a Clinical Trial of Lower-Sodium Oxybate in Participants With Narcolepsy With Cataplexy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A192-A192
Author(s):  
Richard Bogan ◽  
Nancy Foldvary-Schaefer ◽  
Roman Skowronski ◽  
Abby Chen ◽  
Michael Thorpy
Keyword(s):  
Adverse Events ◽  
Study Drug ◽  
Drug Dose ◽  
Sodium Oxybate ◽  
Open Label ◽  
Double Blind ◽  
Peak Incidence ◽  
Safety Population ◽  
Titration Period ◽  
Treatment Naïve

Abstract Introduction This analysis evaluated treatment-emergent adverse events (TEAEs) during a double-blind, placebo-controlled, randomized withdrawal trial (NCT03030599) of lower-sodium oxybate (LXB; Xywav™), an FDA-approved treatment for excessive daytime sleepiness or cataplexy in narcolepsy. Methods At study entry, participants were taking sodium oxybate (SXB) alone, SXB with other anticataplectics, other anticataplectics alone, or were anticataplectic treatment-naive. Participants taking SXB transitioned to the same LXB dose (gram-for-gram); oxybate-naive participants initiated LXB (4.5 g/night). TEAEs were analyzed in the safety population (N=201, received ≥1 study drug dose) during a 12-week open-label optimized treatment/titration period (while other anticataplectics were tapered/discontinued) and subsequent 2-week stable-dose period (SDP). TEAE duration was defined as time from TEAE start to end date (or end of SDP, if TEAE end date was unrecorded). Results LXB-emergent TEAEs varied by treatment at entry. Anticataplectic treatment-naive participants reported TEAEs including headache (n=36/90, 40%; median duration [range]=1 [1–76] day), nausea (n=19/90, 21%; duration=9 [1–37] days), and dizziness (n=15/90, 17%; duration=10 [1–117] days); peak incidence was week 2 (n=8/89, 9%) for headache, week 3 (n=3/88, 3%) for dizziness, and week 1 (n=6/90, 7%) for nausea. Anticataplectic treatment-naive participants (n=13/90, 14%) also reported decreased appetite, with relatively long duration (58 [2–358] days). Participants taking SXB alone reported TEAEs including headache (n=17/52, 33%; duration=1 [1–122] day) and diarrhea (n=4/52, 8%; duration=41 [2–101] days); peak headache incidence was week 4 (n=4/52, 8%); diarrhea had no peak. Participants taking other anticataplectics alone reported TEAEs including headache (n=14/36, 39%; duration=1 [1–94] day), nausea (n=9/36, 25%; duration=3 [1–16] days), and dizziness (n=9/36, 25%; duration=4 [1–29] days); peak incidence was week 1 (n=3/36, 8%) for headache, week 6 (n=2/32, 6%) for nausea, and week 4 (n=3/33, 9%) for dizziness. One participant taking SXB with other anticataplectics (n=1/23, 4%) reported headache in weeks 1–2 and 4; one reported nausea (4%) persisting from week 1 to 8. Overall, study discontinuations attributed to TEAEs were 20/57 (35%). Conclusion Most TEAEs with LXB treatment occurred early, were consistent with the known SXB safety profile, and were relatively short-lived (except decreased appetite). Participants previously taking SXB reported fewer TEAEs than oxybate-naive participants. Support (if any) Jazz Pharmaceuticals, Inc.

The efficacy and safety of roxadustat for anemia in patients with chronic kidney disease: a meta-analysis

2020 ◽  
Author(s):  
Qiyan Zheng ◽  
Huisheng Yang ◽  
Xinwen Fu ◽  
Yishan Huang ◽  
Ruojun Wei ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Placebo Group ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Transferrin Saturation ◽  
Group Versus ◽  
Efficacy And Safety ◽  
Epoetin Alfa ◽  
Electronic Resource ◽  
Quality Evidence

Abstract Background Chronic kidney disease (CKD) is an increasing public health issue. Anemia, which is a complication of CKD, is associated with reduced quality of life and increased morbidity and mortality. Currently quite a few clinical studies have been conducted to compare roxadustat with epoetin alfa [all for dialysis-dependent (DD) patients] or placebo [all for nondialysis-dependent (NDD) patients]. Our meta-analysis aimed to investigate the efficacy and safety of roxadustat for anemia in patients with CKD. Methods We thoroughly searched eight electronic resource databases for randomized controlled trials (RCTs) comparing the efficacy and safety between roxadustat versus epoetin alfa or placebo for the treatment of anemia in patients with CKD. Results Four Phase 2 and two Phase 3 studies with 1010 participants were included. Hemoglobin (Hb) and transferrin levels were increased significantly in the roxadustat group versus those in the placebo {standard mean difference [SMD] 1.57 [95% confidence interval (CI) 1.17–1.98]; SMD 1.81 [95% CI 1.53–2.08]; respectively, both low-quality evidence} or epoetin alfa group [SMD 0.47 (95% CI 0.02–0.93), very low-quality evidence; SMD 1.05 (95% CI 0.81–1.29), low-quality evidence; respectively]. Hepcidin levels were reduced significantly in the roxadustat group versus those in the placebo [SMD −1.72 (95% CI −3.03 to −0.41), very low-quality evidence] or epoetin alfa group [SMD −0.23 (95% CI −0.43 to −0.02), low-quality evidence]. Ferritin and serum transferrin saturation (TSAT) levels were reduced significantly in the roxadustat group versus those in the placebo group [SMD −0.82 (95% CI −1.31 to −0.33); SMD −0.54 (95% CI −0.76 to −0.32), respectively; both low-quality evidence] and ferritin and TSAT levels in the roxadustat group were comparable to those in the epoetin alfa group [SMD 0.02 (95% CI −0.18–0.21); SMD 0.15 (95% CI −0.04–0.35), respectively, both low-quality evidence]. As for safety, the incidence of adverse events (AEs) in the roxadustat group was insignificantly different from that of the placebo group [risk ratio (RR) 0.99 (95% CI 0.83–1.18); P = 0.89, very low-quality evidence]. But the incidence of AEs in the roxadustat group was significantly higher than that in the epoetin alfa group [RR 1.25 (95% CI 1.01–1.54); P = 0.04, low-quality evidence]. There was no significant association between roxadustat and the incidence of serious AEs (SAEs) for both NDD and DD patients [RR 1.08 (95% CI 0.51–2.28) and RR 1.43 (95% CI 0.85–2.40), respectively, both very low-quality evidence]. Conclusion In this meta-analysis of RCTs, we found evidence that after the oral administration of roxadustat, NDD patients’ Hb levels were increased effectively and DD patients’ Hb levels were maintained effectively. The risk of SAEs was not observed with the short-term use of roxadustat. These findings support roxadustat for the treatment of anemia in patients with CKD.

scholarly journals A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial for Evaluation of the Efficacy and Safety of DKB114 on Reduction of Uric Acid in Serum

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3794
Author(s):  
Yu Hwa Park ◽  
Do Hoon Kim ◽  
Jung Suk Lee ◽  
Hyun Il Jeong ◽  
Kye Wan Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Uric Acid ◽  
Placebo Group ◽  
Serum Uric Acid ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Food Ingredient ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Significant Difference

This study sought to investigate the antihyperuricemia efficacy and safety of DKB114 (a mixture of Chrysanthemum indicum Linn flower extract and Cinnamomum cassia extract) to evaluate its potential as a dietary supplement ingredient. This clinical trial was a randomized, 12-week, double-blind, placebo-controlled study. A total of 80 subjects (40 subjects with an intake of DKB114 and 40 subjects with that of placebo) who had asymptomatic hyperuricemia (7.0–9.0 mg/dL with serum uric acid) was randomly assigned. No significant difference between the DKB114 and placebo groups was observed in the amount of uric acid in serum after six weeks of intake. However, after 12 weeks of intake, the uric acid level in serum of subjects in the DKB114 group decreased by 0.58 ± 0.86 mg/dL and was 7.37 ± 0.92 mg/dL, whereas that in the placebo group decreased by 0.02 ± 0.93 mg/dL and was 7.67 ± 0.89 mg/dL, a significant difference (p = 0.0229). In the analysis of C-reactive protein (CRP) change, after 12 weeks of administration, the DKB114 group showed an increase of 0.05 ± 0.27 mg/dL (p = 0.3187), while the placebo group showed an increase of 0.10 ± 0.21 mg/dL (p = 0.0324), a statistically significant difference (p = 0.0443). In the analysis of amount of change in apoprotein B, after 12 weeks of administration, the DKB114 group decreased by 4.75 ± 16.69 mg/dL (p = 0.1175), and the placebo group increased by 3.13 ± 12.64 mg/dL (p = 0.2187), a statistically significant difference between the administration groups (p = 0.0189). In the clinical pathology test, vital signs and weight measurement, and electrocardiogram test conducted for safety evaluation, no clinically significant difference was found between the ingestion groups, confirming the safety of DKB114. Therefore, it may have potential as a treatment for hyperuricemia and gout. We suggest that DKB114 as a beneficial and safe food ingredient for individuals with high serum uric acid. Trial registration (CRIS.NIH. go. Kr): KCT0002840.

scholarly journals Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study

2019 ◽  
Vol 78 (8) ◽  
pp. 1033-1040 ◽  
Author(s):  
Sophie Glatt ◽  
Peter C Taylor ◽  
Iain B McInnes ◽  
Georg Schett ◽  
Robert Landewé ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Certolizumab Pegol ◽  
Inadequate Response ◽  
Proof Of Concept ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Reactive Protein ◽  
Dual Inhibition

ObjectiveEvaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.MethodsDuring this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).ResultsOf 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).ConclusionsPoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.

scholarly journals Topical Propranolol Improves Epistaxis Control in Hereditary Hemorrhagic Telangiectasia (HHT): A Randomized Double-Blind Placebo-Controlled Trial

2020 ◽  
Vol 9 (10) ◽  
pp. 3130
Author(s):  
Meir Mei-Zahav ◽  
Yulia Gendler ◽  
Elchanan Bruckheimer ◽  
Dario Prais ◽  
Einat Birk ◽  
...  
Keyword(s):  
Placebo Group ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Controlled Trial ◽  
Intravenous Iron ◽  
Common Adverse Event ◽  
Open Label ◽  
Two Phase ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Propranolol Group

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (−2.03 ± 1.7 as compared with −0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (−1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

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