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Safety of ciclesonide in children with asthma: A review of randomized controlled trials.

ABSTRACT: Background: Parental concerns about the adverse effects of asthma medications can lead to nonadherence and uncontrolled asthma in children. Ciclesonide (CIC) is a prodrug, with low oropharyngeal deposition and bioavailability that may minimize the risk of local and systemic adverse effects. CIC is U.S. Food and Drug Administration approved for asthma in children ages ≥ 12 years. Objective: To summarize safety results from the 13 phase II or III randomized controlled trials conducted in children with asthma during CIC clinical development. Methods: Four 12- to 24-week trials compared the safety of once-daily CIC 40, 80, or 160 µg/day with placebo; four 12-week trials compared the safety of CIC 80 or 160 µg/day with either fluticasone or budesonide; one 12-month trial compared the long-term safety of CIC 40, 80, or 160 µg/day with fluticasone; one 12-month trial compared growth velocity of CIC 40 or 160 µg/day with placebo; and three cross-over trials compared short-term growth velocity and hypothalamic-pituitary-adrenal (HPA) axis effects of CIC 40, 80, or 160 µg/day with placebo or fluticasone. Results: In all, 4399 children were treated with CIC. The incidence of treatment-emergent adverse events (AE) was similar among the CIC doses and between CIC and placebo in short-term studies and between CIC and fluticasone in the long-term safety study. No CIC-related serious AEs were reported in any study. The incidence of treatment-related oral candidiasis was low and similar between CIC (≤0.5%) and placebo (≤0.7%) or active controls (≤0.5%) in the short-term studies. There was no clinically relevant HPA axis suppression or reduction in growth velocity associated with CIC. Conclusion: Data from 13 studies demonstrate that CIC is associated with low rates of oropharyngeal AEs, with no indication of clinically relevant systemic effects in children with asthma. The favorable safety profile and demonstrated improvements in asthma control make CIC an ideal inhaled corticosteroid for the treatment of asthma in children.

SUBMITTER: Blaiss M

PROVIDER: S-EPMC8654382 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Ciclesonide (CIC) is an inhaled corticosteroid (ICS) approved for the maintenance treatment of asthma in patients ages ≥ 12 years. The prodrug aspect of CIC is associated with a safety profile that may make it ideal for children. Objective: The objective was to summarize efficacy results from the eight phase III, randomized, double-blind, controlled trials in children with asthma conducted during CIC clinical development. Methods: Four trials compared CIC 40, 80, or 160 µg/day with placebo. Two trials compared CIC 160 µg/day with fluticasone propionate 200 µg/day, one trial compared CIC 80 or 160 µg/day with fluticasone 200 µg/day, and one trial compared CIC 160 µg/day with budesonide 400 µg/day. Results: The primary end point was met by at least two CIC doses versus placebo in the trials in which the primary end point was the change from baseline in lung function outcome (forced expiratory volume in 1 second [FEV1] % predicted or morning peak expiratory flow [PEF]). A trial that compared CIC with placebo did not meet the primary end point of superiority in time-to-first severe wheeze exacerbation or lack of improvement. The primary end point of noninferiority to the active control (fluticasone or budesonide) in the change from baseline in a lung function outcome (FEV1, morning PEF, evening PEF) was met with the CIC 160-µg dose in all active control trials. CIC generally demonstrated statistically significant improvements in forced expiratory flow at 25%-75% of forced vital capacity, asthma symptoms, rescue medication use, and asthma control when compared with placebo and noninferiority for these outcomes compared with fluticasone or budesonide. Conclusion: In children with asthma, once-daily CIC significantly improved large and small airway function, asthma symptoms, and asthma control, and reduced rescue medication use compared with placebo. CIC was comparable with other ICS used to treat asthma in children, which demonstrated its worth for the pediatric population.

Project description:Background: Asthma and obesity are major public health problems, affecting hundreds of millions of people worldwide. Obesity is associated with increased asthma risk and severity, and lower asthma-related quality of life. Objective: In this systematic review, we aimed to evaluate whether weight loss in subjects with obesity and asthma leads to improvement in asthma-related outcomes. Data Sources and Extraction: We searched PubMed and Google Scholar for all studies in English published January 2000-December 2018. Studies were included if they were randomized, controlled clinical trials (RCTs) for overweight/obese children or adults with asthma, with sufficient data to assess outcomes and study quality. Non-randomized and non-controlled studies were excluded, as well as those in subjects without overweight/obesity, or with non-asthmatic controls. Synthesis: We identified four RCTs involving children (total n = 246) and six involving adults (n = 502). All interventions were designed for weight loss and varied from dietary restrictions to multifactorial interventions with exercise training and cognitive behavioral therapy; the duration of intervention ranged from 8 weeks to 18 months. All RCTs reported successful improvements in weight or body mass index (-0.14 standard deviation scores to -15.9% BMI reduction in children, 1.8%-14.5% weight loss in adults). RCTs generally reported improvements in asthma-related quality of life and, to some degree, asthma control. RCTs involving adults also reported improvements in lung function (FEV1, FVC, TLC), while RCTs in children showed less consistent results. Conclusions: These findings suggest that weight loss in subjects with obesity and asthma may improve asthma outcomes. However, there was wide variability in populations studied, baseline and post-intervention assessments, follow-up length, outcome definition and reporting, and statistical approaches, which hindered the ability to compare studies, perform a pooled analysis, or assess generalizability. Primary Source of Funding: U.S. National Institutes of Health (NIH).

Project description:Acupoint herbal patching (AHP), which involves local point stimulation with a herbal medicine patch, has long been used to treat patients with asthma in East Asian countries. However, its evidence is equivocal. This systematic review aims to summarize and critically evaluate the efficacy and safety of AHP for asthma.A literature search was conducted in PubMed, EMBASE, the Cochrane library, and the China National Knowledge Infrastructure for studies published on or before April 2014, which were randomized controlled trials (RCTs) examining AHP therapy by itself or in combination with other treatments in asthma patients. Trials needed to report pulmonary function outcomes to be included in analyses. The risk of bias of included studies was assessed using the Cochrane risk of bias assessment tool. For statistical pooling, risk ratio, mean difference (MD), or standardized MD was calculated with 95% confidence intervals (CIs) in a random-effects model.We ultimately included 16 RCTs with 1287 asthmatic patients in analyses. Treatment with AHP improved forced expiratory volume in 1?second (FEV1) by 13% (MD?=?12.99%, 95% CI 5.17%-20.81%) and asthmatic symptoms by 60% (risk ratio of unchanged or getting worse symptoms with AHP?=?0.4, 95% CI 0.27-0.58) over that observed with placebo. However, evidence is limited due to the heterogeneity and paucity of data. When added to conventional therapies, AHP significantly improved the FEV1/forced vital capacity ratio by 11.6% (95% CI 8.49%-14.79%) and reduced the risk of asthmatic symptoms by 69% (95% CI 0.16-0.58). Compared with conventional medication, AHP significantly improved FEV1 (standardized MD?=?0.46, 95% CI 0.05-0.87), but a substantial heterogeneity was detected (I?2=?53%). When added to Chinese herbal medicine, there were no additional benefits of AHP on pulmonary function or global symptom improvement. No serious adverse events were associated with AHP.Evidence for AHP efficacy is encouraging, but not conclusive, because of clinical diversity and the high risk of bias in the examined studies. Further clinical and basic research is needed to determine the role of AHP in lung function and symptom improvement in patients with asthma.

Project description:Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control.To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.The Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization.Participating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157).The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control.The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]).In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events.clinicaltrials.gov Identifier: NCT00442013.

Project description:Loxapine, a first-generation antipsychotic, delivered with a novel inhalation delivery device developed for the acute treatment of agitation in patients with schizophrenia or bipolar disorder was evaluated in subjects with asthma or chronic obstructive pulmonary disease (COPD).Separate randomized, double-blind, parallel-arm, placebo-controlled trials compared two administrations of inhaled loxapine (10?mg) 10?hr apart with placebo in 52 subjects with asthma and in 53 subjects with COPD. A thermally-generated drug aerosol of loxapine was delivered to the deep lung for rapid systemic absorption. Controller medications were continued throughout the study, but quick-relief bronchodilators were withheld from 6-8?hr before through 34?hr after dose 1, unless indicated as rescue.All airway adverse events (AEs) were of mild or moderate severity. Symptomatic bronchospasm occurred in 53.8% of subjects with asthma after inhaled loxapine and 11.5% after placebo; and in 19.2% of COPD subjects after inhaled loxapine and 11.1% after placebo. Subjects required inhaled albuterol as follows: asthma: 53.8% after inhaled loxapine and 11.5% after placebo; and COPD: 23.1% after inhaled loxapine and 14.8% after placebo. Respiratory signs/symptoms requiring treatment responded to rescue bronchodilator [forced expiratory volume in 1?sec (FEV(1)) return to within 10% of baseline] within 1?hr in 11 of 15 events in asthma subjects and four of seven events in COPD subjects, the remainder by the last spirometry.In subjects with either asthma or COPD, FEV(1) decline and bronchospasm can occur following inhaled loxapine, but more frequently in asthmatic subjects. Most subjects with bronchospasm responded to rescue bronchodilator within 1?hr. No treatment-related serious AE occurred. Although inhaled loxapine is contraindicated in patients with active airways disease per the current approved US labeling, these studies demonstrated that rescue bronchodilator mitigated the symptomatic bronchospasms that may occur in case of inadvertent use.

Project description:BackgroundThis systematic review evaluated the effectiveness of process interventions (education for clinicians, parent presence, education of parents [before and on day of vaccination], and education of patients on day of vaccination) on reducing vaccination pain, fear, and distress and increasing the use of interventions during vaccination.Design/methodsDatabases were searched using a broad search strategy to identify relevant randomized and quasi-randomized controlled trials. Critical outcomes were pain, fear, distress (when applicable), and use of pain management interventions. Data were extracted according to procedure phase (preprocedure, acute, recovery, combinations of these) and pooled using established methods. Analyses were conducted using standardized mean differences (SMD) and risk ratios (RR).ResultsThirteen studies were included. Results were generally mixed. On the basis of low to very low-quality evidence, the following specific critical outcomes showed significant effects suggesting: (1) clinicians should be educated about vaccine injection pain management (use of interventions: SMD 0.66; 95% confidence interval [CI]: 0.47, 0.85); (2) parents should be present (distress preprocedure: SMD -0.85; 95% CI: -1.35, -0.35); (3) parents should be educated before the vaccination day (use of intervention preprocedure: SMD 0.83; 95% CI: 0.25, 1.41 and RR, 2.08; 95% CI: 1.51, 2.86; distress acute: SMD, -0.35; 95% CI: -0.57, -0.13); (4) parents should be educated on the vaccination day (use of interventions: SMD 1.02; 95% CI: 0.22, 1.83 and RR, 2.42; 95% CI: 1.47, 3.99; distress preprocedure+acute+recovery: SMD -0.48; 95% CI: -0.82, -0.15); and (5) individuals 3 years of age and above should be educated on the day of vaccination (fear preprocedure: SMD -0.67; 95% CI: -1.28, -0.07).ConclusionsEducating individuals involved in the vaccination procedure (clinicians, parents of children being vaccinated; individuals above 3 y of age) is beneficial to increase use of pain management strategies, reduce distress surrounding with vaccination, and to reduce fear. When possible, parent presence is also recommended for children undergoing vaccination.

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Safety of ciclesonide in children with asthma: A review of randomized controlled trials.

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