Comparison of the efficacy of ciclesonide with that of budesonide in mild to moderate asthma patients after step-down therapy: a randomised parallel-group study.
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ABSTRACT:
SUBMITTER: Chiu KC
PROVIDER: S-EPMC4373304 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:OBJECTIVES:Budesonide/formoterol fumarate (BUD/FF) is recommended in the stepwise management of uncontrolled asthma, but data on a once-daily dose of this medication in a step-down period are lacking. We aimed to compare BUD/FF and BUD in terms of the changes in asthma control scores and lung functions. MATERIAL AND METHODS:This 12-week, randomized, parallel-group, single-center, open-label study was conducted in well-controlled asthmatic patients receiving twice-daily BUD/FF (160/4.5 μg 2 inhalations) randomized into once-daily BUD/FF (160/4.5 μg 1 inhalation) or twice-daily BUD (200 μg 2 inhalations). RESULTS:At week 12, the medians of Asthma Control Test (ACT) were 23 (interquartile range [IQR]: 22-24) in the BUD/FF group and 23 (IQR: 22-24.5) in the BUD group, while the medians of Asthma Control Questionnaire (ACQ) were 0.43 (IQR: 0.29-0.82) in the BUD/FF group and 0.57 (IQR: 0.43-0.93) in the BUD group. No statistically significant difference was observed in either ACT (p=0.673) or ACQ (p=0.295) between the treatments. The ACT scores significantly decreased from baseline to week 12 in both treatments. Peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) also had no statistically significant differences between treatments. PEF in the BUD/FF group and FEV1 in both treatments significantly decreased from baseline to week 12. CONCLUSION:Compared to twice-daily BUD, once-daily BUD/FF provides equivalent asthma control scores and lung function during the step-down period after switching from twice-daily doses of BUD/FF in well-controlled asthma.
| S-EPMC5937812 | biostudies-literature
Project description:BackgroundProinflammatory leukotrienes, which are not completely inhibited by inhaled corticosteroids, may contribute to asthmatic problems [corrected]. A 16 week multicentre, randomised, double blind, controlled study was undertaken to study the efficacy of adding oral montelukast, a leukotriene receptor antagonist, to a constant dose of inhaled budesonide.MethodsA total of 639 patients aged 18-70 years with forced expiratory volume in 1 second (FEV(1)) > or =55% predicted and a minimum predefined level of asthma symptoms during a 2 week placebo run in period were randomised to receive montelukast 10 mg (n=326) or placebo (n=313) once daily for 16 weeks. All patients received a constant dose of budesonide (400-1600 microg/day) by Turbuhaler throughout the study.ResultsMean FEV(1) at baseline was 81% predicted. The median percentage of asthma exacerbation days was 35% lower (3.1% v 4.8%; p=0.03) and the median percentage of asthma free days was 56% higher (66.1% v 42.3%; p=0.001) in the montelukast group than in the placebo group. Patients receiving concomitant treatment with montelukast had significantly (p<0.05) fewer nocturnal awakenings and significantly (p<0.05) greater improvements in beta agonist use and morning peak expiratory flow rate (PEFR).ConclusionsFor patients with mild airway obstruction and persistent asthma symptoms despite budesonide treatment, concomitant treatment with montelukast significantly improves asthma control.
| S-EPMC1746619 | biostudies-literature
Project description:Background and aimsSafety and efficacy of budesonide multimatrix, an oral extended-release second-generation corticosteroid designed for targeted delivery throughout the colon, were examined for induction of remission in patients with mild to moderate ulcerative colitis refractory to baseline mesalamine therapy.MethodsA randomised, double-blind, placebo-controlled, multicentre trial evaluated efficacy and safety of budesonide multimatrix for induction of remission [ulcerative colitis disease activity index score ≥ 4 and ≤ 10] in 510 adults randomised to once-daily oral budesonide multimatrix 9 mg or placebo for 8 weeks. Patients continued baseline treatment with oral mesalamine ≥ 2.4 g/day.ResultsCombined clinical and endoscopic remission at Week 8 was achieved by 13.0% and 7.5% of patients receiving budesonide multimatrix [n = 230] or placebo [n = 228], respectively, in the modified intention-to-treat population [p = 0.049]. Clinical remission [ulcerative colitis disease activity index rectal bleeding and stool frequency subscale scores of 0] was similar in both groups [p = 0.70]. More patients receiving budesonide multimatrix vs placebo achieved endoscopic remission [ulcerative colitis disease activity index mucosal appearance subscale score of 0; 20.0% vs 12.3%; p = 0.02] and histological healing [27.0% vs 17.5%; p = 0.02]. Adverse event rates were similar [budesonide multimatrix, 31.8%; placebo, 27.1%]. Mean morning cortisol concentrations decreased at Weeks 2, 4, and 8 with budesonide multimatrix but remained within the normal range.ConclusionBudesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy.
| S-EPMC5881669 | biostudies-literature
Project description:Budesonide MMX is a novel oral formulation of budesonide that uses Multi-Matrix System (MMX) technology to extend release to the colon. This study compared the efficacy of budesonide MMX with placebo in patients with active, mild-to-moderate ulcerative colitis (UC).Patients were randomised 1:1:1:1 to receive budesonide MMX 9 mg or 6 mg, or Entocort EC 9 mg (budesonide controlled ileal-release capsules; reference arm) or placebo once daily for 8 weeks. The primary endpoint was combined clinical and endoscopic remission, defined as UC Disease Activity Index score ?1 with a score of 0 for rectal bleeding and stool frequency, no mucosal friability on colonoscopy, and a ?1-point reduction in endoscopic index score from baseline.410 patients were evaluated for efficacy. Combined clinical and endoscopic remission rates with budesonide MMX 9 mg or 6 mg, Entocort EC and placebo were 17.4%, 8.3%, 12.6% and 4.5%, respectively. The difference between budesonide MMX 9 mg and placebo was significant (OR 4.49; 95% CI 1.47 to 13.72; p=0.0047). Budesonide MMX 9 mg was associated with numerically higher rates of clinical (42.2% vs 33.7%) and endoscopic improvement (42.2% vs 31.5%) versus placebo. The rate of histological healing (16.5% vs 6.7%; p=0.0361) and proportion of patients with symptom resolution (23.9% vs 11.2%; p=0.0220) were significantly higher for budesonide MMX 9 mg than placebo. Adverse event profiles were similar across groups.Budesonide MMX 9 mg was safe and more effective than placebo at inducing combined clinical and endoscopic remission in patients with active, mild-to-moderate UC.
| S-EPMC3933176 | biostudies-literature
Project description:BackgroundThe use of low-dose inhaled corticosteroid-formoterol as reliever monotherapy has recently been recommended in the asthma treatment guidelines. However, the efficacy of this treatment strategy has not yet been determined during the stepping-down period in moderate asthma. This study aimed to evaluate the feasibility of reducing treatment to as-needed budesonide-formoterol (BFM) in moderate asthma with complete remission.MethodsWe randomly assigned 31 patients (8 males and 23 females with a mean age of 57.2 years) with complete remission of asthma by inhaled BFM (160/4.5 μg) twice daily to receive BFM (160/4.5 μg) as needed (16 patients), or budesonide (BUD) (200 μg) twice daily (15 patients). The study was an open-label study done for 48 weeks, with the primary outcome as the cumulative percentages of patients with treatment failure (asthma exacerbation or loss of asthma control or lack of satisfaction after using medications) in the two groups.ResultsSix patients (42%) using as-needed BFM had treatment failure, as compared with three patients (21.4%) using BUD maintenance (hazards ratio for as-needed BFM, 1.77; 95% confidential interval, 0.44-7.12; p=0.41). The changes in forced expiratory volume in 1 second were -211.3 mL with as-needed BFM versus -97.8 mL with BUD maintenance (difference, 113.5 mL; p=0.75) and the change in fractional exhaled nitric oxide was significantly higher in both groups, at 8.68 parts per billion (ppb) in the as-needed BFM group and 2.5 ppb. in the BUD maintenance group (difference, 6.18 ppb; p=0.049).ConclusionCompared with BUD maintenance, there were no significant differences in treatment failure rate in patients who received as-needed BFM during the stepping down period in moderate asthma. However, they showed reduced lung function and relapsed airway inflammation. The results are limited by imprecision, and further large RCTs are needed.
| S-EPMC9263339 | biostudies-literature
Project description:INTRODUCTION:Dupilumab, a fully human anti-IL-4Rα monoclonal antibody, inhibits signaling of both interleukin (IL)-4 and IL-13, which are key drivers of type 2-mediated inflammation. Dupilumab is approved in the EU, USA, and other countries for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. Following positive phase 2 results in asthma, the phase 3 Liberty Asthma QUEST trial was initiated to provide further evidence for dupilumab efficacy and safety in patients with uncontrolled, moderate-to-severe asthma. METHODS:Liberty Asthma QUEST is a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (NCT02414854) in patients with persistent asthma who are receiving continuous treatment with inhaled corticosteroids (ICS) plus one or two other asthma controller medicines. A total of 1902 patients (aged ≥ 12 years) were randomized in a 2:2:1:1 ratio to receive 52 weeks of add-on therapy with subcutaneously administered dupilumab 200 or 300 mg every 2 weeks or matched placebo. The study consisted of a 4 ± 1-week screening period, 52-week randomized treatment period, and 12-week post-treatment follow-up period. All patients continued to receive their prescribed ICS plus up to two additional controller medications. The primary efficacy endpoints were annualized rate of severe exacerbation events during the 52-week treatment period and absolute change from baseline in pre-bronchodilator FEV1 at week 12. CONCLUSION:Uncontrolled asthma patients with persistent symptoms represent a population of significant unmet need, for whom new treatments are required. Patients with severe asthma are at high risk of asthma exacerbations, and face an accelerated decline in lung function and impaired quality of life. QUEST examines the efficacy of dupilumab in this at-risk patient population; it is the largest placebo-controlled study in uncontrolled, moderate-to-severe asthma with a biologic agent to date, and the only phase 3 study of a biologic therapy of asthma that enrolled patients irrespective of baseline type 2 inflammatory biomarker levels. FUNDING:Sanofi and Regeneron Pharmaceuticals, Inc. CLINICAL TRIALS. GOV IDENTIFIER:NCT02414854.
| S-EPMC5960488 | biostudies-literature
Project description:BackgroundThis study investigated the efficacy and safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform®), administered twice daily (b.i.d.) via a single aerosol inhaler, compared with its individual components administered separately and placebo, in patients with mild-to-moderate asthma.MethodsPatients aged ≥ 12 years were evenly randomised to 12 weeks of treatment with fluticasone/formoterol (100/10 μg b.i.d.), fluticasone (100 μg b.i.d.), formoterol (10 μg b.i.d.), or placebo, in this double-blind, parallel group, multicentre study. The three co-primary endpoints were: a) change in forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 for the comparison with formoterol; b) change in FEV(1) from morning pre-dose at baseline to 2 hours post-dose at week 12 for the comparison with fluticasone, and c) time to discontinuation due to lack of efficacy from baseline to week 12 for the comparison with placebo. Safety was assessed based on adverse events, clinical laboratory tests and vital sign evaluations.ResultsStatistically significant differences were demonstrated for all the three co-primary endpoints. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in pre-dose FEV(1) compared with formoterol (Least Squares (LS) mean treatment difference: 0.101 L; 95% Confidence Interval (CI): 0.002, 0.199; p = 0.045) and the change in pre-dose compared with 2 hours post-dose FEV(1) versus fluticasone (LS mean treatment difference: 0.200 L; 95% CI: 0.109, 0.292; p < 0.001). The time to discontinuation due to lack of efficacy was significantly longer for patients in the combination therapy group compared with those receiving placebo (p = 0.015). Overall, the results from multiple secondary endpoints assessing lung function, asthma symptoms, and rescue medication use supported the superior efficacy of the combination product compared with fluticasone, formoterol, and placebo. The fluticasone/formoterol combination therapy had a good safety and tolerability profile over the 12 week treatment period.ConclusionsFluticasone/formoterol had a good safety and tolerability profile and showed statistically superior efficacy for the three co-primary endpoints compared to fluticasone, formoterol, and placebo, in adolescents and adults with mild-to-moderate asthma. EudraCT number: 2007-002866-36; US NCT number: NCT00393991.
| S-EPMC3502550 | biostudies-literature
Project description:The comparative effectiveness of different inhaler therapies in mild-to-moderate asthma remains unclear. To assess this, we performed a systematic review and network meta-analysis of randomized controlled trials on the use of inhalers for mild-to-moderate asthma by searching PubMed, Cochrane, and Embase. A total of 29 trials including 43,515 patients and 12 types of inhaler therapies were included. For the prevention of severe and moderate-to-severe exacerbations, inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) as maintenance and reliever (SMART) showed the highest rank for effectiveness. As-needed ICS/LABA or short-acting β2-agonist (SABA) was similar to low-dose ICS and superior to as-needed SABA or LABA for the prevention of severe and moderate-severe exacerbations. As for lung function (FEV1), low-dose ICS/LABA had the highest rank; as-needed ICS/LABA was inferior to regular low-dose ICS but superior to placebo. Higher-dose ICS had a superior effect on the Asthma Control Questionnaire (ACQ) scores, and as-needed ICS/LABA and as-needed SABA or LABA had lower ranks in p-rankogram than did the regular use of low-dose ICS. As-needed ICS with LABA or SABA was more effective than a similar dose of regular ICS for preventing exacerbation in mild-to-moderate asthma. As-needed ICS showed some weakness in improving lung function and controlling asthma symptoms.
| S-EPMC8993836 | biostudies-literature
Project description:In many patients with mild asthma, the low frequency of symptoms and the episodic nature of exacerbations make adherence to regular maintenance treatment difficult. This often leads to over-reliance on short-acting ?2-agonist (SABA) reliever medication and under-treatment of the underlying inflammation, with poor control of asthma symptoms and increased risk of exacerbations. The use of budesonide/formoterol 'as needed' in response to symptoms may represent an alternative treatment option for patients with mild asthma.The SYmbicort Given as needed in Mild Asthma (SYGMA) programme consists of two 52-week, double-blind, randomised, multicentre, parallel-group, phase 3 trials of patients aged 12 years and older with a clinical diagnosis of asthma for at least 6 months, who would qualify for treatment with regular inhaled corticosteroids (ICS). SYGMA1 aims to recruit 3750 patients who will be randomised to placebo twice daily (bid) plus as-needed budesonide/formoterol 160/4.5 ?g, placebo bid plus as-needed terbutaline 0.4 mg, or budesonide 200 ?g bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the superiority of as-needed budesonide/formoterol over as-needed terbutaline for asthma control, as measured by well-controlled asthma weeks; a secondary objective is to establish the noninferiority of as-needed budesonide/formoterol versus maintenance budesonide plus as-needed terbutaline using the same outcome measure. SYGMA2 aims to recruit 4114 patients who will be randomised to placebo bid plus as-needed budesonide/formoterol 160/4.5 ?g, or budesonide 200 ?g bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the noninferiority of as-needed budesonide/formoterol over budesonide bid plus as-needed terbutaline as measured by the annualised severe exacerbation rate. In both studies, use of all blinded study inhalers will be recorded electronically using Turbuhaler® Usage Monitors.Given the known risks of mild asthma, and known poor adherence with regular inhaled corticosteroids, the results of the SYGMA programme will help to determine the efficacy and safety of as-needed budesonide/formoterol therapy in mild asthma. Patient recruitment is complete, and completion of the phase 3 studies is planned in 2017.ClinicalTrials.gov identifiers: NCT02149199 SYGMA1 and NCT02224157 SYGMA2. Registered on 16 May 2014 and 19 August 2014, respectively.
| S-EPMC5223341 | biostudies-literature
Project description:Background:A recent study shows that dual antiplatelet therapy with clopidogrel plus aspirin is superior to aspirin monotherapy for minor stroke, which is defined as a National Institutes of Health Stroke Scale (NIHSS)score of ?3. However, acute mild-moderate ischaemic stroke (4?NIHSS?10) still needs aggressive antiplatelet intervention to prevent deterioration and recurrence of stroke. The efficacy and safety of dual antiplatelet therapy versus aspirin monotherapy in the population are not clear. A multicentre clinical trial is designed to evaluate the efficacy and safety of clopidogrel plus aspirin therapy versus aspirin monotherapy within 48?hours of symptom onset of mild-moderate ischaemic stroke. Methods/Design:The study is a randomised, open-label, multicentre, prospective trial with a target enrolment of 2700 patients from 60 centres in Northeast China. A treatment allocation identification number to each enrolled patient will be provided by a random number generator. The follow-up time for the clopidogrel plus aspirin and aspirin monotherapy groups is 90 days. The primary efficacy endpoint is a stroke progression event, which is defined as ?4?point increase in the NIHSS score in 48?hours. The second efficacy endpoints include new ischaemic stroke within 90 days, change in the NIHSS score within 14?days, modified Rankin Scale score on day 90 and other vascular or death events within 90 days. The safety endpoints include mucocutaneous haemorrhage, organ haemorrhage and intracranial haemorrhage, adverse events and severe adverse events. ?2 test, t-test (or Mann-Whitney test), survival analysis and Cox proportional hazards models will be conducted. The findings of the study may provide an important evidence for clinical practice for these patients. Discussion:The trial will be conducted under a rational design and will provide valuable evidence on the appropriate treatment for this population. Ethics and dissemination:The study was reviewed and approved by the Ethics Committee of the General Hospital of Shen-Yang Military Region (no K(2016) 6). Trial registration number:NCT02869009; Pre-results.
| S-EPMC6312068 | biostudies-literature