Stacking Exercises Attenuate the Decline in Forced Vital Capacity and Sick Time (STEADFAST)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 18
- 主要终点
- Change in FVC (%-Predicted) From Baseline to 2 Years.
研究概览
简要总结
Duchenne Muscular Dystrophy is complicated by weak breathing muscles and lung infections. "Lung volume recruitment" is a technique performed using a face mask or mouthpiece and a hand-held resuscitation bag to stack breaths, inflate the lungs and help clear the airways of secretions by increasing the forcefulness of a cough. We believe this will slow down the steady loss of lung function, prevent lung infection, and improve quality of life. Our aim is to compare the outcome of a group of individuals with DMD treated with standard care to another group that also receives lung volume recruitment. If effective, this study will change clinical practice by including twice-daily treatment as part of the standard of care for individuals with DMD, in order to improve their lung health and quality of life.
详细描述
Background: Respiratory complications are the primary cause of morbidity and mortality associated with childhood Duchenne Muscular Dystrophy (DMD). Involvement of the respiratory muscles leads to progressive hypoventilation and/or recurrent atelectasis and pneumonia secondary to decreased cough efficacy. Lung volume recruitment (LVR) is a means of stacking breaths to achieve maximal lung inflation (MIC), prevent micro-atelectasis, and improve cough efficacy. Although it has been recommended by some experts as the "standard of care" for individuals with neuromuscular disease, the strategy has not been widely implemented in DMD given the lack of clinical trials to date to support its efficacy as well as the additional burden of care required in a population already requiring multiple interventions.
Primary Objective: To determine whether LVR, in addition to conventional treatment, is successful in reducing decline from baseline in forced vital capacity (FVC) over 2 years (percent predicted, measured according to American Thoracic Society standards), compared to conventional treatment alone in children with DMD.
Secondary Objectives: To determine differences between children treated with LVR in addition to conventional treatment, compared to those treated with conventional treatment alone, in: (1) the number of courses of antibiotics, hospitalizations and intensive care admissions for respiratory exacerbations, (2) health-related quality of life, and (3) peak cough flow and other pulmonary function tests.
Methods: We propose a 3-year multi-centre randomized controlled trial involving fifteen tertiary care pediatric hospitals across Canada. The study population consists of boys aged 6-16 years with DMD and FVC ≥ 30% of predicted. A sample size of 110 participants will be enrolled. This has been informed by chart review and survey of participating centres to be feasible, and will be re-assessed with an ongoing internal pilot study. Intervention: Participants will be allocated with a minimization procedure to receive conventional treatment (non-invasive ventilation, nutritional supplementation, physiotherapy and/or antibiotics, as decided by the treating physician) or conventional treatment plus twice daily LVR exercises performed with an inexpensive, portable self-inflating resuscitation bag containing a one-way valve and a mouthpiece. Data Analysis: The primary outcome (change in percent predicted FVC over 2 years) will be compared between the two study groups using an analysis of co-variance (ANCOVA) that takes into account baseline FVC and minimization factors.
Importance: Decline in pulmonary function among children with DMD negatively affects quality of life and predicts mortality. The relatively simple strategy of LVR has the potential to optimize pulmonary function and reduce respiratory exacerbations, thereby improving quality of life for individuals with DMD. This study is novel in that it is the first randomized controlled trial of LVR. A major strength is that the results will give support or refute recommendations regarding inclusion of LVR in the standard of care for individuals with DMD worldwide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 6 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6-16 years - This age range was selected as there are accepted normative pulmonary function data and children 6 years of age and older are generally able to reliably perform pulmonary function tests. Children are followed in participating centres until they reach 18 years of age (allowing two years of follow-up).
- •Clinical phenotypic features consistent with DMD and confirmed by either: (1) Muscle biopsy showing complete dystrophin deficiency; (2) Genetic test positive for deletion or duplication in the dystrophin gene resulting in an 'out-of-frame' mutation; or (3) Dystrophin gene sequencing showing a mutation associated with DMD.
- •FVC ≥ 30% predicted - This range of pulmonary function was selected to exclude those with severe restrictive respiratory impairment, who are less likely to be able to reliably perform pulmonary function testing over a two year period.
- •A caregiver willing to provide the therapy
- •Fluency in English or French
排除标准
- •Unable to perform pulmonary function tests and/or LVR manoeuvre
- •Presence of an endotracheal or tracheostomy tube
- •Already using LVR and/or the Respironics in-exsufflator between and during respiratory infections
- •Known susceptibility to pneumothorax or pneumomediastinum
- •Uncontrolled asthma or other obstructive lung disease
- •Symptomatic cardiomyopathy (ejection fraction less than 50% )
研究组 & 干预措施
Conventional Treatment
Conventional Treatment
干预措施: Conventional Treatment (Other)
Lung Volume Recruitment
Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day
干预措施: Lung Volume Recruitment (LVR) (Device)
Lung Volume Recruitment
Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day
干预措施: Conventional Treatment (Other)
结局指标
主要结局
Change in FVC (%-Predicted) From Baseline to 2 Years.
时间窗: 2 years
Change in FVC (%-predicted) was chosen as the primary outcome as it is a strong predictor of subsequent respiratory failure and mortality. Although survival is not a realistic endpoint for this trial, given expected mortality is less than 5% for the pediatric age group, FVC change is an appropriate clinical laboratory measure and valid surrogate endpoint to use for this trial.
次要结局
- FVC Decline of 10% of Predicted(2 years)
- Number of Participants Prescribed Outpatient Oral Antibiotic Courses Between Baseline and 2 Years(2 years)
- Health-related Quality of Life From Baseline to 2 Years(2 years)
- Change in Difference Between Assisted and Unassisted Peak Cough Flow (PCF) From Baseline to 2 Years(2 years)
- Change in Maximal Insufflation Capacity (MIC)-Vital Capacity (VC) From Baseline to 2 Years(2 years)
- Change in Maximum Inspiratory Pressures (MIP), From Baseline to 2 Years(2 years)
- Change in Maximal Expiratory Pressures (MEP), From Baseline to 2 Years(2 years)
研究者
Sherri Katz
Dr. Sherri Katz
Children's Hospital of Eastern Ontario