Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β
-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited.
We ...compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD.
The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). A patient subgroup remained on blinded treatment for up to 52 weeks. Co-primary endpoints were change from baseline in trough FEV
and in St. George's Respiratory Questionnaire (SGRQ) total score at Week 24.
In the intent-to-treat population (n = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899), mean changes from baseline in FEV
were 142 ml (95% confidence interval CI, 126 to 158) and -29 ml (95% CI, -46 to -13), respectively, and mean changes from baseline in SGRQ scores were -6.6 units (95% CI, -7.4 to -5.7) and -4.3 units (95% CI, -5.2 to -3.4), respectively. For both endpoints, the between-group differences were statistically significant (P < 0.001). There was a statistically significant reduction in moderate/severe exacerbation rate with triple therapy versus dual ICS/LABA therapy (35% reduction; 95% CI, 14-51; P = 0.002). The safety profile of triple therapy reflected the known profiles of the components.
These results support the benefits of single-inhaler triple therapy compared with ICS/LABA therapy in patients with advanced COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02345161).
The frequency of COPD exacerbations during treatment with a triple inhaler — delivering a long-acting beta-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled glucocorticoid — ...was compared with that with a LABA–LAMA or LABA–inhaled glucocorticoid.
The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone ...furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations. Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.
Report ACM and impact of stepping down therapy, following collection of additional vital status data.
Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg following a run-in on their COPD therapies. Time to ACM was prespecified. Additional vital status data collection and subsequent analyses were performed
.
We report vital status data for 99.6% of the intention-to-treat population (
= 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI. For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99;
= 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16;
= 0.387) versus FF/VI. Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient's COPD.
In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations.
To the Editor:
In his review article, Maron (Aug. 16 issue)
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does not mention the potential of physical examination in patients with hypertrophic cardiomyopathy (HCM). In addition to history taking, ...physical examination is still a cornerstone in clinical medicine, and cardiac auscultation, in particular, is considered to be synonymous with clinical cardiology,
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although collective skills in auscultation have reportedly declined.
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The physical signs of HCM may depend to some extent on the presence of a systolic pressure gradient within the left ventricle, which is detected in 70% of patients with this condition.
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Far beyond a sophisticated description of physical findings, . . .
Among more than 11,000 patients with moderate-to-severe asthma, fluticasone–salmeterol was noninferior to fluticasone alone with respect to severe asthma events.
The safe and appropriate use of ...short-acting beta-agonists (SABAs) and long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated.
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In early reports, SABAs were associated with an increased risk of asthma-related death.
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In the 1990s, analyses suggested that high use of SABAs (>1.5 to 2 canisters per month) might increase the risk of death or near-fatal asthma.
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In one of these studies, the authors postulated that high use of SABAs was either a marker of poorly controlled asthma or a “toxic effect of the medications or their vehicles.”
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Two large clinical trials, the Serevent Nationwide . . .
Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on ...healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting β2-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10 000 patients from approximately 1070 centres. Eligible patients are aged ≥40 years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12 months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017.
Patients with chronic obstructive pulmonary disease (COPD) have excess risk of developing pneumonia; however, no definitive biomarkers of risk have been established. We hypothesized that blood ...neutrophils would help predict pneumonia risk in COPD.
A meta-analysis of randomized, double-blind clinical trials of COPD patients meeting the following criteria were selected from the GlaxoSmithKline trial registry: ≥1 inhaled corticosteroid-containing (ICS) arm (fluticasone propionate/salmeterol or fluticasone furoate/vilanterol), a control arm (non-ICS), pre-randomization blood neutrophil counts, ≥24-week duration. The number of patients with pneumonia events and time to first event (Kaplan-Meier analysis) were evaluated (post-hoc), stratified by baseline blood neutrophil count and ICS use. A Cox proportional hazards model was used to calculate hazard ratios (HR), split by median baseline blood neutrophils.
Ten studies (1998 to 2011) with 11,131 patients were identified. The ICS (n = 6735) and non-ICS (n = 4396) cohorts were well matched in neutrophil distributions and demographics. Increasing neutrophil count was associated with an increased proportion of patients with pneumonia events; patients below the median neutrophil count were at less risk of a pneumonia event (HR, 0.75 95% confidence interval 0.61-0.92), and had longer time to a first event, compared with those at/above the median. The increase in pneumonia risk by neutrophil count was similar between the two cohorts.
Increased blood neutrophils in COPD were associated with increased pneumonia risk, independent of ICS use. These data suggest blood neutrophils may be a useful marker in defining treatment pathways in COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This large trial involving children with asthma examined whether the addition of a long-acting beta-agonist to current therapy with inhaled glucocorticoids affected asthma control in children. The ...primary safety end point was within the prespecified noninferiority margin.
The safety of inhaled beta-agonists in patients with asthma has been debated since the 1960s.
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After the introduction of long-acting beta-agonists (LABAs) in the 1990s and the findings of two studies involving adults, attention focused on a potential association of LABAs with an increased risk of asthma-related death.
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A 2008 meta-analysis conducted by the Food and Drug Administration (FDA) showed a higher risk of asthma-related events (death, intubation, or hospitalization) among patients receiving LABAs than among patients not receiving these medications.
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In a subsequent meta-analysis, a higher risk of serious asthma-related events was observed with salmeterol than with . . .
Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. ...Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial.
BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome.
BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases.
Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019.
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