scholarly journals Exhalation Delivery Systems for Application of Intranasal Corticosteroids

2020 ◽  
pp. 014556132098019
Author(s):  
Alexander J. Kovacs ◽  
Nithin D. Adappa ◽  
Edward C. Kuan
Keyword(s):  
Nasal Cavity ◽  
Delivery System ◽  
Paranasal Sinuses ◽  
Safety Data ◽  
Sinus Surgery ◽  
Topical Steroids ◽  
Efficacy And Safety ◽  
Open Label ◽  
Safety And Efficacy ◽  
Patient Reported

Background: Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient’s forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system. Methods: Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies. Results: The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU. Conclusion: Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS.

scholarly journals Efficacy and Safety of Long-Term Low-Dose Clarithromycin in Patients With Refractory Chronic Sinusitis After Endoscopic Sinus Surgery: A Prospective Clinical Trial

2021 ◽  
pp. 014556132110320
Author(s):  
Han Chen ◽  
Bing Zhou ◽  
Qian Huang ◽  
Cheng Li ◽  
Yubin Wu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Nasal Cavity ◽  
Endoscopic Sinus Surgery ◽  
Low Dose ◽  
Continuous Treatment ◽  
Sinus Surgery ◽  
Efficacy And Safety ◽  
Endoscopic Findings ◽  
Before And After

Objective: To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication. Methods: This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously. Results: A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea ( P < .05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment ( P < .05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed. Conclusion: Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota.

Development of the Paranasal Sinuses in Children: Implications for Paranasal Sinus Surgery

1993 ◽  
Vol 102 (9) ◽  
pp. 705-711 ◽  
Author(s):  
Gerald Wolf ◽  
Wolfgang Anderhuber ◽  
Frederick Kuhn
Keyword(s):  
Nasal Cavity ◽  
Paranasal Sinus ◽  
Paranasal Sinuses ◽  
Age Groups ◽  
Clinical Importance ◽  
Sinus Surgery ◽  
Clinical Anatomy ◽  
Surgical Interventions ◽  
Stage Of Development ◽  
Paranasal Sinus Surgery

The pediatric nasal cavity and paranasal sinuses, when compared to those in adults, differ not only in size but also in proportion. Knowledge of the unique anatomy and pneumatization of children's sinuses is an important prerequisite to understanding the pathogenesis of sinusitis and its complications. It is also important in evaluation of radiographs and in planning surgical interventions. In order to study the development of the paranasal sinuses in children and relate clinical anatomy to sinus surgery, the sinuses in 102 pediatric skulls and cadaver heads were measured. The results were classified by stage of development into 4 different age groups: newborn and 1 to 4, 4 to 8, and 8 to 12 years. The characteristics of each group and their clinical importance for paranasal sinus surgery are described.

scholarly journals Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

2014 ◽  
Vol 41 (5) ◽  
pp. 837-852 ◽  
Author(s):  
Jürgen Wollenhaupt ◽  
Joel Silverfield ◽  
Eun Bong Lee ◽  
Jeffrey R. Curtis ◽  
Susan P. Wood ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Incidence Rate ◽  
Kinase Inhibitor ◽  
Safety Data ◽  
Janus Kinase ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Safety And Efficacy ◽  
Mean Values ◽  
Link Type

Objective.To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).Methods.Data were pooled from 2 open-label studies (NCT00413699, NCT00661661) involving patients who had participated in qualifying phase I, II, or III index studies of tofacitinib. Safety data included over 60 months of observation; efficacy data are reported up to Month 48. Treatment was initiated with tofacitinib 5 or 10 mg twice daily. Primary endpoints were adverse events (AE) and laboratory safety data. Secondary endpoints included American College of Rheumatology (ACR) response rates, and Disease Activity Score (28 joints) (DAS28)-4[erythrocyte sedimentation rate (ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) assessments.Results.Overall, 4102 patients were treated for 5963 patient-years; mean (maximum) treatment duration was 531 (1844) days; 20.8% of patients discontinued treatment over 60 months. The most common AE were nasopharyngitis (12.7%) and upper respiratory tract infection (10.5%). Serious AE were reported in 15.4% of patients with an exposure-estimated incidence rate of 11.1 events/100 patient-years. Serious infections were reported in 4.5% of patients with an exposure-estimated incidence rate of 3.1 events/100 patient-years (95% CI: 2.66–3.55). Mean values for laboratory variables were stable over time and consistent with phase II and III studies. Persistent efficacy was demonstrated through Month 48, as measured by ACR response rate (ACR20/50/70) DAS28-4-ESR, and HAQ-DI. Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background nonbiologic disease-modifying antirheumatic drugs.Conclusion.Tofacitinib demonstrated consistent safety and persistent efficacy over 48 months in patients with RA.

scholarly journals DOP73 Efficacy and safety of escalation to tofacitinib 10 mg BID for patients with UC following loss of response on 5 mg BID maintenance therapy: Results from OCTAVE open-label, long-term extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S110-S111 ◽  
Author(s):  
B E Sands ◽  
A C Moss ◽  
A Armuzzi ◽  
J K Marshall ◽  
J O Lindsay ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Treatment Failure ◽  
Induction Therapy ◽  
Dose Escalation ◽  
Safety Data ◽  
Mucosal Healing ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Open Label

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib have been demonstrated in patients with moderate to severe UC in three Phase 3 studies (OCTAVE Induction 1 and 2 [NCT01465763; NCT01458951]; OCTAVE Sustain [NCT01458574]) [1]. Here, we present updated efficacy and safety data of tofacitinib dose escalation in patients with UC participating in an ongoing, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) [2]. Methods We present updated data from the dose-escalation subpopulation of the OLE study (as of May 2019; database not locked) comprising patients who achieved clinical response (CR) following 8 weeks of tofacitinib 10 mg twice daily (BID) induction therapy, entered OCTAVE Sustain receiving tofacitinib 5 mg BID, experienced treatment failure between Week 8 and Week 52, and subsequently entered OCTAVE Open with escalation to tofacitinib 10 mg BID. Treatment failure was defined as an increase of ≥3 points from maintenance study baseline total Mayo score, plus an increase of ≥1 point in both rectal bleeding subscore and centrally read endoscopic subscore (ES), and an absolute ES of ≥2 after ≥8 weeks of maintenance therapy. CR, mucosal healing (MH) and remission (R) were evaluated at Months 2, 12, 24 and 36 of OCTAVE Open (non-responder imputation and last observation carried forward [NRI-LOCF] and observed data). Safety was evaluated throughout the study. Results Of 944 patients enrolled in the OLE study, the dose escalation subpopulation comprised 59 patients. In these patients, CR, MH and R rates 36 months after dose escalation were, respectively, 40.7%, 39.0% and 30.5% for NRI-LOCF and 95.2%, 86.4% and 66.7% for observed data (Table). Of these 59 patients, 29 had prior tumour necrosis factor inhibitor (TNFi) failure; in these patients, CR, MH and R rates at Month 36 were, respectively, 51.7%, 51.7% and 41.4% for NRI-LOCF, and 100.0%, 92,3% and 75.0% for observed data. Incidence rates for safety events and pt-years’ exposure are reported in the table. Conclusion For most patients who lost initial CR to tofacitinib 10 mg BID induction therapy while on tofacitinib 5 mg BID maintenance therapy, including those with prior TNFi failure, dose-escalation back to 10 mg BID recaptured CR by Month 2 and was generally maintained over 3 years. The safety profile with tofacitinib 10 mg BID in the dose-escalation subpopulation was generally consistent with that in the overall study population, although there was a numerically higher rate of herpes zoster. These analyses are limited by low pt numbers and the absence of a comparator arm. References

scholarly journals P219 Long-term safety of filgotinib in patients with PsA: week 52 safety data from a Phase 2 open-label extension study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Laura Coates ◽  
Philip Mease ◽  
Dafna Gladman ◽  
Filip Van den Bosch ◽  
Anna Rychlewska-Hanczewska ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

Preliminary results of a phase II trial of FOLFOX4 regimen in Chinese patients with unresectable primary liver cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14065-14065 ◽  
Author(s):  
S. K. Qin ◽  
Y. J. Wang ◽  
Q. Wu ◽  
B. C. Xing
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Phase Ii ◽  
Primary Liver Cancer ◽  
Safety Data ◽  
Median Number ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Open Label ◽  
Number Of Cycles

14065 Background: Primary liver cancer (PLC) is the 3rd most common cancer in whole China. Development of systemic chemotherapy for the patients not eligible for operation as well as TACE commonly have been required. Oxalipaltin (Eloxatin)+ 5-FU/LV, namely FOLFOX 4 regimen was tried to investigate its efficacy and safety in inoperable PLC. Methods: It was an open-label, single arm and multi-center phase II study to explore RR, DCR,TTP and MST. All the pts had pathologically confirmed inoperable PLC with/without distant metastasis. The pts were treated with the standard FOLFOX 4 regimen, that is OXA 85mg/m2 d1; LV 200mg/m2 IV 2hrs d1,2; 5-FU 400mg/m2 bolus, d1,2 and 5-FU 600mg/m2 CIV 22hrs d1,2; q2w upto 6 cycles or until progression. Tumor evaluation was done every 6 weeks using RECIST criteria. Neurotoxicity was evaluated by Eloxatin specific neurotoxicity criteria (Sanofi-Aventis Co.Ltd) and other toxicities by the NCI CTC AE version 2.0. Results: From July 2004 to Sep. 2005, 27 pts (21 male, 6 female) were recruited from the 4 cancer centers with average age of 56 ±13 years old. 25 patients (92.6%) had hepatocellular carcinoma, and 2 (7.4%) cholangiocellular carcinoma. 15 pts (55.6%) had metastatic disease. 1 pt received liver transplantation before inclusion. The median number of cycles was 4 per pt. 26 pts were evaluable for efficacy and safety. The RR was 19.2% (5/26; 1 CR and 4 PR), and DCR 57.7% (15/26; including 10 SD). 4 of the 5 responsive pts had hepatocellular carcinoma, and 1 had cholangiocarcinoma. Serum AFP level was significantly decreased (mean 131,890.4ug/dl at the baseline and 1,298.6ug/dl after 6 cycles) for the first 16 pts. The first 16 pts’ safety data were available in detail: 11 NCI grade 3/4 events were observed from a total of 76 cycles administered: including 5 neutropenia, 3 leucopenia, 1 thrombocytopenia, 1 infection and 1 liver dysfunction. Grade II & III neurotoxicity was found in 3 & 2 patients respectively. The TTP,MST and further safety data were under follow-up. Conclusions: The preliminary data of the FOLFOX 4 regimen for the advanced Chinese pts with inoperable PLC have shown encouraging results with the better efficacy and favorable safety profile. Further exploration in this area is warranted, especially in hepatocellular carcinoma. No significant financial relationships to disclose.

Efficacy and safety results from AvaALL: An open-label, randomized phase III trial of standard of care (SOC) with or without continuous bevacizumab (Bev) treatment beyond progression (PD) in patients (pts) with advanced non-small cell lung cancer (NSCLC) progressing after first-line Bev and chemotherapy (chemo).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9004-9004 ◽  
Author(s):  
Jaafar Bennouna ◽  
Javier De Castro ◽  
Anne-Marie C. Dingemans ◽  
Frank Griesinger ◽  
Francesco Grossi ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Safety Data ◽  
Phase Iii ◽  
Positive Trend ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Phase Iii Trial ◽  
Significance Level ◽  
Safety Signals

9004 Background: The role of treatment with Bev beyond PD is unclear in the multiline treatment strategy of advanced NSCLC.AvaALL(NCT01351415), a multinational, open-label, randomized phase III trial, assessed continuous Bev and SOC beyond first PD (PD1) in pts with NSCLC following first-line treatment with platinum-based chemo plus Bev. Here we present efficacy and safety data from AvaALL. Methods: Pts with NSCLC who received 4–6 cycles of chemo + Bev and ≥2 cycles of maintenance Bev were randomized after PD1 to second-line SOC therapy (docetaxel, pemetrexed or erlotinib) ± Bev. After second PD (PD2) and third PD (PD3), pts received third-line or fourth-line SOC ± Bev treatment, respectively. Primary endpoint was overall survival (OS). Secondary endpoints were OS rates (6, 12, and 18-months [mos]), progression-free survival (PFS) from PD1 to PD2/from PD2 to PD3, overall response rate (ORR), disease control rate (DCR), and safety. Data cut-off: 24 Jun 2016. Results: Overall, 485 pts were randomized (n = 475 treated). Pt characteristics were well balanced between the two arms. Bev plus chemo resulted in a median OS of 11.9 mos versus 10.2 mos for SOC alone (HR 0.84, 90% CI 0.71–1.00; p = 0.1016; 387 OS events). The primary endpoint was not met (416 OS events were required, at 10% two-sided significance level). OS rates were 10% higher in the Bev arm vs SOC alone at 6-, 12- and 18-mos. Median PFS2 was 4.9 mos with Bev vs 3.8 mos with SOC (HR 0.85, 90% CI 0.72–1.00; p = 0.0907). PFS3 was significantly improved (3.5 mos for Bev, 2.4 mos for SOC; HR 0.65, 90% CI 0.51–0.84; p = 0.0047). ORR and DCR were slightly higher in the Bev arm versus the SOC arm (ORR 9.7% vs 6.7%; DCR 86.2% vs 79.3%, respectively). No new safety signals were identified. Grade ≥3 adverse events were reported in 78.2% of Bev pts and 61.6% of SOC pts. Conclusions: Although the primary endpoint was not met, efficacy data suggest a positive trend for continued Bev plus SOC after PD1 compared with SOC alone. No cumulative safety signals were identified. Clinical trial information: NCT01351415.

scholarly journals TOPICAL DECONSTANTS IN PEDITRIC PRACTICE

2017 ◽  
pp. 44-47
Author(s):  
A. D. BARATASHVILI ◽  
E. P. KARPOVA
Keyword(s):  
Nasal Cavity ◽  
Paranasal Sinuses ◽  
Inflammatory Diseases ◽  
Efficacy And Safety

The article tells about the use, efficacy and safety of vasoconstrictive and irrigation medications in children with inflammatory diseases of the nasal cavity and paranasal sinuses

scholarly journals Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ashim Gupta ◽  
Nicola Maffulli ◽  
Hugo C. Rodriguez ◽  
R. Justin Mistovich ◽  
Kristin Delfino ◽  
...  
Keyword(s):  
Stem Cell ◽  
Magnetic Resonance ◽  
Prospective Study ◽  
Open Label ◽  
Safety And Efficacy ◽  
Knee Oa ◽  
Symptomatic Knee ◽  
Essential Components ◽  
Patient Reported ◽  
Grade Ii

Abstract Background Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA. Methods and analysis This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration. Discussion This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA. Trial registration Registered on July 21, 2021. ClinicalTrials.gov NCT04971798

scholarly journals Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003421
Author(s):  
Delphine Sculier ◽  
Gilles Wandeler ◽  
Sabine Yerly ◽  
Annalisa Marinosci ◽  
Marcel Stoeckle ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Adverse Events ◽  
Viral Suppression ◽  
Safety Data ◽  
Risk Difference ◽  
Hiv Treatment ◽  
Efficacy And Safety ◽  
Open Label ◽  
Hiv 1

Background Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. Methods and findings SIMPL’HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel–Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than −12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference −1.2%; 95% CI −7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI −5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference −1.1%; 95% CI −9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study’s main limitations included a rather small proportion of women included, the open label design, and its short duration. Conclusions In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals. Trial registration ClinicalTrials.gov NCT03160105.

Sign in / Sign up

Export Citation Format

Share Document