Primary Effectiveness Endpoint Research Articles

Drug-Eluting Stent Versus Drug-Coated Balloon Revascularization in Patients With Femoropopliteal Arterial Disease

BackgroundRandomized trials of drug-eluting stents (DES) and drug-coated balloons (DCB) for femoropopliteal interventions reported superior patency rates for both strategies compared to standard balloon angioplasty. To date, head-to-head comparisons are missing. ObjectivesThe authors sought to compare DES versus DCB for femoropopliteal lesions through 36 months. MethodsWithin a multicenter, randomized trial, 150 patients with symptomatic femoropopliteal disease were randomly assigned to primary DES implantation or DCB angioplasty with bailout stenting after stratification for lesion length (≤10 cm, >10 cm to ≤20 cm, and >20 cm to ≤30 cm). The primary effectiveness endpoint was primary patency at 12 months assessed by Kaplan-Meier. Secondary endpoints comprised major adverse events including death, major amputations, and clinically driven target lesion revascularization, and clinical outcomes. ResultsMore than one-half of lesions were total occlusions, and the stenting rate was 25.3% in the DCB group. Kaplan-Meier estimates of primary patency were 79% and 80% for DES and DCB at 12 months (p = 0.96) but decreased to 54% and 38% through 36 months (p = 0.17), respectively. Freedom from clinically driven target lesion revascularization was >90% at 12 months but dropped to around 70% at 36 months in both groups. Overall, the mortality rate through 36 months was 7.3%, with 1 procedure-related death in the DCB group. Improvement of clinical outcomes was sustained through 36 months. ConclusionsPatency rates at 12 months suggest comparable effectiveness and safety of DES versus DCB plus bailout stenting in femoropopliteal interventions; a trend in favor of the DES was observed up to 36 months. (Randomized Evaluation of the Zilver PTX Stent vs. Paclitaxel-Eluting Balloons for Treatment of Symptomatic Peripheral Artery Disease of the Femoropopliteal Artery [REAL PTX]; NCT01728441)

Long-Term Clinical Outcomes after Mix and Match Implantation of Two Multifocal Intraocular Lenses with Different Adds.

Purpose To compare long-term clinical outcomes between patients with bilateral implantation of +3.0 diopter (D) multifocal intraocular lenses (IOLs) and mix and match implantation of +2.5 D and +3.0 D multifocal IOLs. Material and Methods This retrospective observer-masked cohort study comprised 66 eyes of 33 patients with two different strategies of binocular multifocal IOLs implantation: bilateral +3.0 D (17 patients) (bilateral group) and mix and match +2.5 D and +3.0 D (16 patients) (blended group). Patients were recruited 1 year (±3 months) after second-eye surgery. The primary effectiveness endpoint was binocular uncorrected intermediate visual acuity (UCIVA) at 70 cm. The secondary assessments included binocular visual quality tests and quality-of-vision questionnaire. Results The blended group showed clinically better UCIVA (0.10 ± 0.07 logMAR) at 70 cm than the bilateral group (0.26 ± 0.09 logMAR) with a difference of 0.16 ± 0.08 logMAR (P < 0.001). Similar binocular visual acuities were achieved between the two groups at the near and far distance. The binocular defocus curves showed better performance in the blended group from 50 cm to 1 m. The mean binocular contrast sensitivities under the photopic conditions with or without glare and mesopic condition without glare were clinically better in the blended group. Both the groups reported low rate of visual phenomena, high rate of spectacle independence, and satisfaction. Conclusions Comparing with bilateral implantation of +3.0 D multifocal IOLs during the cataract surgery, mix and match implantation of +2.5 D and +3.0 D multifocal IOLs provides a wider depth of binocular focus, especially for intermediate distances, and better binocular visual quality.

Tocilizumab Effectiveness After Switching from Intravenous to Subcutaneous Route in Patients with Rheumatoid Arthritis: The RoSwitch Study

IntroductionThe main objective of this work was to assess the maintenance of effectiveness of subcutaneous tocilizumab 6 months after switching from intravenous to subcutaneous formulation in patients with rheumatoid arthritis (RA) in a real-world setting. Secondary objectives aimed to describe the characteristics of patients and disease, the effectiveness at 12 months after switching, the therapeutic maintenance, and to search for predictive factors of switching.MethodsWe analyzed all the RA patients of the shared medical file “RIC Nord de France”, treated with tocilizumab, switching or not from intravenous to subcutaneous tocilizumab, between April 2015 and January 2016. The primary effectiveness endpoint was the proportion of patients remaining in their DAS28-ESR category remission/low disease activity (LDA) or moving to an inferior DAS28-ESR category at 6 months. Since RoSwitch was an observational study, without randomization, a propensity score was built in a sensitivity analysis to balance on RA and patients’ characteristics at inclusion between switching and no-switching groups.ResultsAn improvement of initial DAS28-ESR category or maintenance in DAS28-ESR remission/LDA at 6 months was shown in 203 of the 285 patients with an evaluation for the primary criterion (71.2%, 95% CI [65.6–76.4%]) without differences between groups (73.3%, 95% CI [63.0–82.1%] vs. 70.3%, 95% CI [63.3–76.6%]). The RoSwitch study showed the maintenance of effectiveness at 6 and 12 months. Similar therapeutic maintenance rates were observed for switch and no-switch patients. No clinical factor was associated with the switch in patients in remission/LDA at inclusion.ConclusionsThe RoSwitch study showed the maintenance of effectiveness at 6 months in RA patients switching from intravenous (IV) to subcutaneous (SC) tocilizumab.FundingRoche SAS and Chugai Pharma France.Electronic supplementary materialThe online version of this article (10.1007/s40744-018-0138-y) contains supplementary material, which is available to authorized users.

Randomized, Controlled, Double-Masked, Multicenter, Pilot Study Evaluating Safety and Efficacy of Intranasal Neurostimulation for Dry Eye Disease.

We assess the safety and effectiveness of intranasal neurostimulation to promote tear production via the nasolacrimal pathway in subjects with dry eye disease. A multicenter, randomized, controlled, double-masked pilot study was conducted in adults with dry eye diagnosis and at least one eye with corneal fluorescein staining ≥2 in at least one region or a sum of all regions ≥5 (National Eye Institute grading), basal Schirmer test score ≤10 mm, a cotton-swab stimulated Schirmer score ≥7 mm higher, and an Ocular Surface Disease Index score ≥23. Subjects were randomized to receive active intranasal neurostimulation or sham control intranasal stimulation 4 to 8 times per day. Assessments were scheduled before (unstimulated) and during (stimulated) device application at days 0, 7, 14, 30, and 90. The primary effectiveness endpoint was stimulation-induced change in Schirmer test (with anesthesia) score. Primary safety measure was incidence of device-related adverse events (AEs). Fifty-eight subjects were randomized at nine sites in Australia and New Zealand; 56 completed the 90-day study. Stimulation-induced change in Schirmer score was significantly greater with active intranasal (mean ± SEM, 9.0 ± 2.0) than sham control intranasal stimulation (0.4 ± 0.6; P < 0.001) at day 90. Similar results were observed at days 0, 7, 14, and 30 (P < 0.001). No serious device-related AEs were observed. Mild nosebleed, the most common device-related AE, was reported in five (16.7%) subjects. Intranasal neurostimulation was effective in inducing acute tear production after 90 days of use and generally was well tolerated in subjects with dry eye disease.

TearCare® system extension study: evaluation of the safety, effectiveness, and durability through 12 months of a second TearCare® treatment on subjects with dry eye disease.

PurposeEvaluation of the safety and effectiveness of a TearCare® retreatment in adult subjects with clinically significant dry eye disease (DED).Patients and methodsThis was an extension of an initial 6-month, prospective, single-center, randomized, parallel-group pilot study. In the initial study, subjects with DED were randomized to either a single TearCare® treatment or 4 weeks of daily warm compress therapy. The extension study involved retreatment of those subjects assigned to the TearCare® treatment group following the initial 6-month end point. At 6 months, subjects were evaluated for the clinical signs and symptoms of DED prior to retreatment in the extension study that would measure the safety, effectiveness, and durability of a TearCare® retreatment for another 6 months through a 12-month end point. The TearCare® retreatment procedure consisted of 12 minutes of thermal eyelid treatment immediately followed by manual meibomian gland clearance. The primary effectiveness end point was the change in tear break-up time (TBUT) from baseline to 1-month follow-up. Secondary end points included meibomian gland scores, corneal and conjunctival staining scores, and assessment of dry eye symptoms. Safety was evaluated through monitoring intraocular pressure, best-corrected visual acuity, and device-related adverse events.ResultsTwelve subjects participated in the 6-month extension study. At 1-month clinic visit following retreatment, a significant improvement from baseline in mean (± SD) TBUT of 12.4 (±3.3) seconds was observed (P<0.001). Significant improvements in the mean change from baseline in meibomian gland scores, corneal and conjunctival staining scores, and symptoms of DED were also observed following retreatment. The second treatment was well tolerated.ConclusionThe findings of the extension study through 12 months suggest that a second TearCare® treatment after 6 months provides additional improvement in the signs and symptoms of DED.

Percutaneous pulmonary valve implantation in patients with right ventricular outflow tract dysfunction: a systematic review and meta-analysis.

Background:Pulmonary valve replacement is required for patients with right ventricular outflow tract (RVOT) dysfunction. Surgical and percutaneous pulmonary valve replacement are the treatment options. Percutaneous pulmonary valve implantation (PPVI) provides a less-invasive therapy for patients. The aim of this study was to evaluate the effectiveness and safety of PPVI and the optimal time for implantation.Methods:We searched PubMed, EMBASE, Clinical Trial, and Google Scholar databases covering the period until May 2018. The primary effectiveness endpoint was the mean RVOT gradient; the secondary endpoints were the pulmonary regurgitation fraction, left and right ventricular end-diastolic and systolic volume indexes, and left ventricular ejection fraction. The safety endpoints were the complication rates.Results:A total of 20 studies with 1246 participants enrolled were conducted. The RVOT gradient decreased significantly [weighted mean difference (WMD) = −19.63 mmHg; 95% confidence interval (CI): −21.15, −18.11; p < 0.001]. The right ventricular end-diastolic volume index (RVEDVi) was improved (WMD = −17.59 ml/m²; 95% CI: −20.93, −14.24; p < 0.001), but patients with a preoperative RVEDVi >140 ml/m² did not reach the normal size. Pulmonary regurgitation fraction (PRF) was notably decreased (WMD = −26.27%, 95% CI: −34.29, −18.25; p < 0.001). The procedure success rate was 99% (95% CI: 98–99), with a stent fracture rate of 5% (95% CI: 4–6), the pooled infective endocarditis rate was 2% (95% CI: 1–4), and the incidence of reintervention was 5% (95% CI: 4–6).Conclusions:In patients with RVOT dysfunction, PPVI can relieve right ventricular remodeling, improving hemodynamic and clinical outcomes.

Transcatheter Mitral-Valve Repair in Patients with Heart Failure

BackgroundAmong patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.MethodsAt 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%.ResultsOf the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001).ConclusionsAmong patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.)

Primary outcomes and mechanism of action of intravascular lithotripsy in calcified, femoropopliteal lesions: Results of Disrupt PAD II.

DISRUPT PAD II was designed to evaluate the safety and performance of intravascular lithotripsy (IVL), a novel approach using pulsatile sonic pressure waves, to modify intimal and medial calcium in stenotic peripheral arteries. Vascular calcification restricts vessel expansion, increases the risk of vascular complications, and may impair the effect of anti-proliferative therapy. Disrupt PAD II was a non-randomized, multi-center study that enrolled 60 subjects with complex, calcified peripheral arterial stenosis at eight sites. Patients were treated with IVL and followed to 12-months. The primary safety endpoint was major adverse events (MAE) through 30 days. The primary effectiveness endpoint was patency at 12 months as adjudicated by duplex ultrasonography (DUS). Key secondary endpoints included acute procedure success, freedom from re-intervention, and functional outcomes. Between June 2015 and December 2015, subjects with moderate or severe calcified arterial lesions were enrolled. The final residual stenosis was 24.2%, with an average acute gain of 3.0 mm. The 30-day MAE rate was 1.7% with one grade D dissection that resolved following stent placement. Primary patency at 12 months was 54.5%, and clinically driven TLR at 12 months was 20.7%. Optimal IVL technique defined by correct balloon sizing and avoiding therapeutic miss, improved 12-month primary patency and TLR outcomes to 62.9% and 8.6%, respectively. IVL demonstrated compelling safety with minimal vessel injury, and minimal use of adjunctive stents in a complex, difficult to treat population.

The safety and effectiveness of the LVIS stent system for the treatment of wide-necked cerebral aneurysms: final results of the pivotal US LVIS trial

IntroductionThe LVIS stent system (LVIS and LVIS Junior) is a self-expanding, retrievable, microstent system indicated for the treatment of wide-necked cerebral aneurysms (WNAs). The present pivotal study was performed to...

A17651 Renal denervation for resistant hypertension in patients less than 65-year-old

Objectives: To investigate the safety and mid-term efficacy of renal denervation (RDN) in less than 65-year-old Chinese patients with resistant hypertension. Methods: In the prospective cohort study, the patients with resistant hypertension were continuously enrolled to undergo RDN between November 2012 and November 2014 using LEPU single-electrode ablation catheter. The primary effectiveness endpoints were reductions in office blood pressure and 24-hour ambulatory blood pressure (24h-ABP) at six months. The primary safety endpoint was the incidence of major adverse event through 6 months. Results: A total of 50 consecutive patients, aged between 26 and 62 (41.9 ± 10.6) years old, were enrolled, in which 18 (36.0%) were female. At six months after surgery, the office BP and 24-h ABP were separately reduced by 23.7 ± 14.5/11.5 ± 7.9 mmHg and 11.1 ± 8.5/7.1 ± 6.2 mmHg, with the reduction of the number of antihypertensive agents from 4.0 (4.0∼4.0) at baseline to 4.0 (3.0∼4.0) (all P < 0.01). There is no significant change of renal function (P > 0.05) and no major adverse events occurred. Only one patient suffered from femoral artery pseudoaneurysm with no sequelae. Conclusion: RDN seems to be safe and effective in lowering BP in the less than 65-year-old Chinese cohort with resistant hypertension.

Single intra-articular injection of lightly cross-linked hyaluronic acid reduces knee pain in symptomatic knee osteoarthritis: a multicenter, double-blind, randomized, placebo-controlled trial.

The primary objective was to demonstrate the safety and effectiveness of Monovisc™ in the relief of joint pain in patients with idiopathic knee OA compared to saline injection. It was hypothesized that patient success, defined as ≥ 50% improvement from baseline and ≥ 20mm absolute improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) visual analog scale (VAS) pain score, would be greater in the Monovisc™ group compared to the Saline control group. In this multicenter, double-blind, randomized, placebo-controlled trial, patients with idiopathic, symptomatic, knee OA were randomized to either 4ml single injection of Monovisc™ or 4ml injection of 0.9% saline. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess patient outcomes at 2, 4, 8, 12, 20, and 26 weeks post-injection. The primary effectiveness endpoint was a 50% improvement and ≥ 20mm improvement from baseline in the WOMAC pain through 26 weeks. Secondary outcome measures included a ≥ 20mm improvement from baseline on the WOMAC physical function, patient global assessment, evaluator global assessment, and knee range of motion. 369 patients (154 male, 215 female) were randomized to either Monovisc™ or saline. The Monovisc™ group had a significantly greater rate of patient success (e.g. ≥ 50% improvement and ≥ 20mm absolute improvement from baseline in the WOMAC pain through Week 26) compared to saline (p = 0.043). Monovisc™, a single-injection intra-articular HA device, is a safe and effective treatment for providing a clinically meaningful reduction in knee pain within 2 weeks. The results of this study support the use of a single injection of hyaluronic acid (Monovisc™) for patients with symptomatic knee OA in patients older than 45 years, as a safe and effective alternative for patients who may want an alternative treatment modality or may not be candidates for partial or total knee replacement. I, multicenter, double-blind, randomized, placebo-controlled trial.

Cardiovascular Outcomes Assessment of the MitraClip in Patients with Heart Failure and Secondary Mitral Regurgitation: Design and rationale of the COAPT trial

Patients with heart failure (HF) and symptomatic secondary mitral regurgitation (SMR) have a poor prognosis, with morbidity and mortality directly correlated with MR severity. Correction of isolated SMR with surgery is not well established in this population, and medical management remains the preferred approach in most patients. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial was designed to determine whether transcatheter mitral valve (MV) repair with the MitraClip device is safe and effective in patients with symptomatic HF and clinically significant SMR. The COAPT trial is a prospective, randomized, parallel-controlled, open-label multicenter study of the MitraClip device for the treatment of moderate-to-severe (3+) or severe (4+) SMR (as verified by an independent echocardiographic core laboratory) in patients with New York Heart Association class II-IVa HF despite treatment with maximally tolerated guideline-directed medical therapy (GDMT) who have been determined by the site's local heart team as not appropriate for MV surgery. A total of 614 eligible subjects were randomized in a 1:1 ratio to MV repair with the MitraClip plus GDMT versus GDMT alone. The primary effectiveness end point is recurrent HF hospitalizations through 24 months, analyzed when the last subject completes 12-month follow-up, powered to demonstrate superiority of MitraClip therapy. The primary safety end point is a composite of device-related complications at 12 months compared to a performance goal. Follow-up is ongoing, and the principal results are expected in late 2018. HF patients with clinically significant SMR who continue to be symptomatic despite optimal GDMT have limited treatment options and a poor prognosis. The randomized COAPT trial was designed to determine the safety and effectiveness of transcatheter MV repair with the MitraClip in symptomatic HF patients with moderate-to-severe or severe SMR.

Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography

ObjectivesThe aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI. BackgroundCI-AKI is a common complication of percutaneous coronary procedures, associated with increased morbidity and mortality. The AVERT system alters the coronary injection pressure profile by diverting contrast away from the patient during coronary injection. MethodsThe AVERT trial was a prospective, multicenter, 1:1 randomized clinical trial in 578 subjects with either baseline estimated glomerular filtration rate 20 to 30 ml/min/1.73 m2 or estimated glomerular filtration rate 30 to 60 ml/min/1.73 m2 and at least 2 additional risk factors for CI-AKI. Patients undergoing coronary angiography with planned or possible percutaneous coronary intervention (PCI) were randomized to hydration plus the AVERT system (n = 292) or hydration only (n = 286). The primary effectiveness endpoints were: 1) the total CMV used; and 2) the incidence of CI-AKI, defined as a ≥0.3 mg/dl increase in serum creatinine within 5 days post-procedure. ResultsPatient demographics were well balanced between the groups, with mean baseline serum creatinine of 1.6 ± 0.4 mg/dl and 64.9% patients with diabetes mellitus. PCI was performed in 42.2% of procedures, with coronary angiography in the remainder. Use of AVERT resulted in a 15.5% relative reduction in CMV overall (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml; p = 0.02) and a 22.8% relative reduction in CMV among PCI patients (114 ± 55 ml vs. 147 ± 81 ml; p = 0.001). The maximum relative reduction in CMV was 46% (124 ± 48 ml vs. 232 ± 97 ml; p = 0.01) when ≥3 lesions were treated. There were no differences in the rates of CI-AKI (27.0% vs. 26.6%; p = 0.70) between the study groups. ConclusionsUse of the AVERT system was feasible and safe, with acceptable image quality during coronary angiography and PCI. AVERT significantly reduced CMV, with the extent of CMV reduction correlating with procedural complexity. No significant differences in CI-AKI were observed with AVERT in this trial. (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN [AVERT]; NCT01976299)

Drug Coated Balloon Angioplasty in Failing AV Fistulas: A Randomized Controlled Trial.

Restenosis remains a problem in hemodialysis access interventions. Paclitaxel-coated balloons have shown promise in reducing access-related restenosis in small trials. The primary hypotheses for our multicenter trial were superior effectiveness at 180 days and noninferior safety at 30 days of a drug-coated balloon compared with conventional angioplasty for treatment of dysfunctional arteriovenous fistulas. This randomized trial enrolled 285 patients with dysfunctional arteriovenous fistulas at 23 centers. Grafts, central venous stenoses, thrombosed fistulas, and immature fistulas were excluded. All patients received angioplasty of the lesion responsible for access dysfunction. After successful angioplasty (≤30% residual stenosis), lesions were treated with either a paclitaxel-coated balloon or an uncoated control balloon of similar design to the drug-coated balloon. Access function during follow-up was determined per centers' usual protocols; reintervention was clinically driven. The primary efficacy outcome assessment was done at 6 months, and the safety assessment was done within 30 days of the procedure. Prespecified secondary end points included assessment of postintervention target lesion primary patency and access circuit primary patency at 6 months. The 180-day end point was not met with target lesion primary patency (71%±4% for the drug-coated balloon and 63%±4% for control; P=0.06), representing a difference of 8%±6% (95% confidence interval, -3% to 20%). Access circuit primary patency did not differ between groups. Interventions to maintain target lesion patency were fewer for the drug-coated balloon at 6 months (0.31 versus 0.44 per patient; P=0.03). The primary safety noninferiority end point was met and did not differ between groups (P=0.002). Paclitaxel-coated balloon-assisted angioplasty did not meet the primary effectiveness end point at 180 days compared with conventional angioplasty. Both arms showed equivalent safety (ClinicalTrials.gov number NCT02440022).

A Prospective, Multicenter, Pivotal Trial to Evaluate the Safety and Effectiveness of the AEGEA Vapor Endometrial Ablation System

To evaluate the safety and effectiveness of the AEGEA Vapor System (Aegea Medical System, Menlo Park, CA) for the treatment of heavy menstrual bleeding (HMB). A prospective, multicenter, single-arm, open-label, clinical trial. Follow-up assessments were conducted at 24hours; 2weeks; and 3, 6, and 12 months after the endometrial ablation procedure (Canadian Task Force Classification II-1). A private practice and outpatient and hospital settings at 15 sites in the United States, Canada, Mexico, and the Netherlands. One hundred fifty-five premenopausal women aged 30 to 50years with HMB as determined by a pictorial blood loss assessment score ≥150. Preoperative evaluation included ultrasound, sonohysterography or hysteroscopy, and endometrial biopsy. Screening inclusion allowed treatment of up to 12-cm uterine sound lengths and nonobstructing myomata. Endometrial ablation (120-second treatment time) was performed under varying anesthesia regimens using the vapor system from September 2014 to May 2015. The primary effectiveness end point was the reduction of menstrual blood loss to a pictorial blood loss assessment score ≤75. Success was judged based on the Food and Drug Administration's objective performance criteria, derived from the success rates of the first 5 global endometrial ablation pivotal clinical trials. The secondary effectiveness end points included quality of life and patient satisfaction as assessed using the Menorrhagia Impact Questionnaire and the Aberdeen Menorrhagia Severity Score as well as the need for surgical or medical intervention to treat abnormal bleeding at any time within the first 12 months after treatment. All adverse events, including device- and procedure-related events, were recorded. At 12 months, the primary effectiveness end point was achieved in 78.7% of subjects exceeding the OPC (p = .0004); 90.8% of subjects were satisfied or very satisfied with the treatment. Ninety-nine percent of subjects showed improvement in quality of life scores with an average decrease in the Menorrhagia Impact Questionnaire score by 8.1, 72% had less dysmenorrhea, and 85% of women whose sex lives were affected by their menses reported improvement in their sex lives. There were no reported serious adverse device effects or any reported serious adverse events that were procedure related. The AEGEA Vapor System is a safe, effective, and minimally invasive option for performing in-office endometrial ablation under minimal anesthesia for the purpose of treating women who suffer from HMB.

Metformin monotherapy in children and adolescents with type 2 diabetes mellitus in Japan

To evaluate the safety and effectiveness of metformin monotherapy for 52weeks, including 24weeks of treatment and a 28-week extension period for evaluation of long-term safety, in 37 Japanese pediatric patients with type 2 diabetes mellitus. This study design was an open-label, non-randomized, multicenter trial. The primary effectiveness endpoint was the changes from baseline to the final visit at 24weeks in HbA1c. The secondary endpoints were the rate for achieving the treatment goal, and the changes in glycated albumin, fasting blood glucose, fasting insulin, HOMA-IR, and fasting serum lipids. Metformin was administrated at the dose of 500mg/day up to a maximum of 2000mg/day taken in two or three divided doses. The mean change of HbA1c at the final visit at 24weeks for 20 metformin-naïve patients (Group A) was - 0.66 ± 0.95% and that of 17 already-on metformin patients (Group B) was - 0.98 ± 1.62%. These figures proved the effectiveness of metformin as defined before the study. Secondary effectiveness endpoints were also improved. The improvement of blood glucose, fasting insulin and serum lipid levels proved the effectiveness of metformin without increasing body weight. Adverse effects such as nausea and diarrhea were observed in 35 of the 37 subjects and drug-related adverse events were observed in 19 patients. However, these events were not serious and did not increase with long-term treatment. Metformin is safe and effective for Japanese pediatric patients with T2DM.

A Schlemm Canal Microstent for Intraocular Pressure Reduction in Primary Open-Angle Glaucoma and Cataract: The HORIZON Study

To compare cataract surgery with implantation of a Schlemm canal microstent with cataract surgery alone for the reduction of intraocular pressure (IOP) and medication use after 24 months. Prospective, multicenter, single-masked, randomized controlled trial. Subjects with concomitant primary open-angle glaucoma (POAG), visually significant cataract, and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg. Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc, Irvine, CA) in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months. The primary and secondary effectiveness end points were the proportion of subjects demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and adverse events. A total of 369 eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by ≥20% in 77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference= 19.5%, 95% confidence interval [CI] 11.2%-27.8%, P < 0.001). The mean reduction in 24-month unmedicated MDIOP was -7.6±4.1 mmHg (mean ± standard deviation) in the HMS group and -5.3±3.9 mmHg in the NMS group (difference= -2.3 mmHg; 95% CI, -3.0 to -1.6; P < 0.001). The mean number of medications was reduced from 1.7±0.9 at baseline to 0.3±0.8 at 24 months in the HMS group and from 1.7±0.9 to 0.7±0.9 in the NMS group (difference = -0.4 medications; P < 0.001). There were no serious ocular adverse events related to the microstent, and no significant differences in safety parameters between the 2 groups. This 24-month multicenter randomized controlled trial demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone.

Patient-reported outcomes with initiation of fluticasone furoate/vilanterol versus continuing usual care in the Asthma Salford Lung Study

The Asthma Salford Lung Study demonstrated the effectiveness and safety of initiating once-daily inhaled fluticasone furoate/vilanterol (FF/VI) versus continuing usual care (UC) in asthma patients in UK primary care [1]. Here, we report a detailed analysis of patient-reported outcome (PRO) endpoints. Adults with symptomatic asthma maintained on inhaled corticosteroids (ICS) ± long-acting beta2-agonists (LABA) were randomized 1:1 to initiate FF/VI (100 [200]/25 μg) or continue UC. PROs were measured using the Asthma Control Test (ACT), Standardized Asthma Quality of Life Questionnaire (AQLQ [S]), Work Productivity and Activity Impairment: asthma questionnaire, and EQ-5D-3L (EuroQol 5-Dimensions 3-Levels) questionnaire, at timepoints across the 12-month study period. The individual components of ACT response (total score ≥20 or improvement from baseline ≥3) both contributed to the composite primary effectiveness endpoint at Week 24, with odds ratios favoring FF/VI over UC in both cases. Patients initiating FF/VI versus continuing UC were more likely to maintain/improve asthma control, regardless of baseline control status. The odds of patients being responders on AQLQ (S) total score and on individual AQLQ domains at Week 52 were significantly higher for FF/VI versus UC (all p < .001). FF/VI was associated with significantly greater reductions in overall work and activity impairment due to asthma (both p < .001), and a significantly greater change from baseline in EQ visual analogue scale score (p = .007), versus UC at Week 52. PRO findings were consistent across baseline ICS and ICS/LABA subsets. Initiation of FF/VI versus continuing UC was associated with consistent improvements in PROs.

Prospective multicenter clinical trial to evaluate the safety and effectiveness of a new glistening-free one-piece acrylic toric intraocular lens.

PurposeGlistening formation in the intraocular lens (IOL) optic has the potential to impact quality of vision. The enVista One-Piece Hydrophobic Acrylic Spherical IOL Model MX60 (MX60 IOL) is currently the only US Food and Drug Administration-approved IOL with a label of “no glistenings”. The purpose of this prospective, multicenter, partially randomized, partially controlled, double-masked, pivotal study was to evaluate the safety and effectiveness of the enVista One-Piece Hydrophobic Acrylic MX60T Toric IOL (enVista MX60T Toric IOL).Patients and methodsSubjects (n=191) were implanted with the enVista MX60T Toric IOL (cylinder powers 1.25, 2.00, or 2.75 D) or the parent MX60 IOL (control). Eyes within the lowest range of corneal astigmatism were randomized to receive either Toric 1.25 D IOL or control IOL in a 1:1 ratio. All subjects with corneal astigmatism requiring 2.00 or 2.75 D cylinder IOLs received toric IOLs. Rotational stability, cylinder reduction, and best-corrected distance visual acuity were primary effectiveness endpoints measured at Visit 4 (120–180 days postoperatively).ResultsVisit 4 mean absolute axis misalignment in the All Toric group was 4.68°±7.33°, and all subjects had ≤5° absolute rotation from Visit 3 to Visit 4. The 1.25 D group had significantly greater improvement in dioptric cylinder reduction (P<0.001), percent cylinder reduction (P<0.001), and mean uncorrected distance visual acuity (P<0.001), compared to control at Visit 4. Most adverse events (AEs) were mild, with no serious AEs in the study eyes. The rates of cumulative AEs through Visit 4 were below International Organization for Standardization (ISO) standard 11979-7 AE rates.ConclusionenVista MX60T Toric IOL is safe and effective for patients with preoperative corneal astigmatism undergoing IOL implantation.

Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial

Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications. RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic-diastolic hypertension aged 18-75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426. Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (-8·5 mm Hg, SD 9·3) than with the sham procedure (-2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: -6·3 mm Hg, 95% CI -9·4 to -3·1, p=0·0001). No major adverse events were reported in either group. Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic-diastolic hypertension in the absence of medications. ReCor Medical.