The Cardiopulmonary Effect of Inhaled Beta-2-agonists on Adult Ventrucular Septal Defect Patients With Persistant or Surgically Corrected Conditions - The VENTI Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Peek Exercise Oxygen Uptake (ml O2/kg/min) in VSD-operated patientes
研究概览
简要总结
The overall objective for this study is to test whether β2-agonists will affect the cardiopulmonary capacity of VSD-operated patients compared with un-operated VSD-patients and healthy age- and gender-matched controls.
详细描述
- Background information
1.1. Investigational product Ventoline® 0,1 mg/dosis inhalation spray.
The active substance is Salbutamol. Salbutamol is a selective β2-agonist which induces relaxation of the bronchial smooth muscles. Common side effects experienced in 1-10% of chronic Ventoline® users are tachycardia, cephalgia and tremors. For more information about the product go to 12. Appendix 1 - Product summary, which holds the Danish product resume from The Danish Health and Medicines Authority.
1.2 Background Grown-ups with congenital heart disease represent a constantly growing cohort (1,2), and with a birth prevalence of 2.62 per 1000 live birth, isolated ventricular septal defect (VSD) is the most frequent congenital cardiac malformation (3,4). For these patients short- and long-term follow-up studies have displayed low complication rates (5-7), and VSD-corrected patients have been assumed to be just as healthy and physically fit compared as their peers (8). Nevertheless recent studies have demonstrated significant long-term abnormalities (9-12).
Compared with the normal population similar workloads in ergometer cycle test have been demonstrated in some studies (13-17) whereas other studies have observed subnormal working capacity in these VSD patients (18-20). The most recent study, demonstrated significantly lower cardiopulmonary exercise capacity (9), a lower force frequency response (10), and abnormal ventilation pattern compared with healthy age and gender matched controls (11). How the abnormal pulmonary function interrelates with the impaired cardiac function and the limited exercise capacity remains to be clarified. None of the referred studies have explained the mechanism for the impaired exercise capacity. However, chronotropic incompetence (9,14,15,19,21) due to postsynaptic β-adrenergic desensitization of the cardiac autonomic nervous system after corrective cardiac surgery (14,15,19,21) have been suggested. Intrinsic sinus node dysfunction in postoperative congenital heart disease patients has also been demonstrated and may explains the lower exercise capacity (22,23). Moreover, abnormal pulmonary function has been demonstrated in these patients, which may be due to a direct mechanical limitation to breathing caused by the sternotomy the patient underwent earlier in life. However, there may also be an indirect physiological explanation to the abnormal exercise ventilation. A previous study found that the pulmonary function was somewhat decreased in many of the standard parameters, perhaps pointing in the direction of a direct mechanical restriction, but without any clear results(24). The study lacks a reference group of healthy controls, using standardized pulmonary values instead. Moreover, the patient group only consisted of children, not adults, making it difficult to predict the long-term outcome in this group of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 26 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •≥18 years of age and legally competent to vouch for their own study participation.
- •Informed and written consent for participation in this trial.
- •Trial group 1: Surgically corrected for isolated VSD between 1990 and 1998 at Aarhus University Hospital.
- •Trial group 2: Diagnosed with isolated VSD born between 1985 and 1998 without surgical or percutaneous closure. Verified by Echocardiography within the last 4 years. If it is more than 4 it will be verified by our doctors as a systolic murmur or echocardiography.
- •Trial group 3: 18-30 years, with no known medical records of heart and lung disease.
- •Restrain from strenuous leg exercise 24 hours before inclusion.
排除标准
- •Lack of medical record.
- •Pregnancy.
- •o Participants will be asked if they are using contraceptives and be told to continue this during the trial and for at least 30 hours (5 times T2) after their last visit. If they are not using spiral or valid contraceptives (contraceptive pills, implants, transdermal patches, vaginal ring or injections) one of our medical experts will judge if the participant is able to undergo the trial. They will likewise be informed to withstand from sexual intercourse during the trial until 30 hours after the second visit.
- •Currently breastfeeding.
- •Syndromes, such as Down's.
- •Mentally or physically incompetent to perform the ergometer bicycle test.
- •Thyrotoxicosis.
- •Pre-trial medical record of arrhythmias except right bundle branch block.
- •Asthma or other known β2-responsive conditions.
- •Coronary heart disease.
- •Severe pulmonary disease.
- •Diabetes.
- •Use of the following medication: Xantin-derivates, steroids, diuretics, ipratropium.
- •Allergy to the active ingredients of Ventoline: Salbutamolsulphate, benzalkoniumchloride
- •The product summary was used to establish exclusion criteria in regards to medication and diseases that aren't eligible with the medical treatment. Other medication than described in the in- and exclusion criteria will be noted in the participants CRF. If the participant takes any special medication one of our trial doctors will determine if the participant should be excluded.
- •Participants will be informed of the exclusion criteria in the information letter and at the initial information interview before inclusion in the trial. Oral verification is considered sufficient to verify the exclusion criteria.
研究组 & 干预措施
Operated VSD's
Through the use of Electronic Patient Journal (EPJ), the investigators have identified a total of 182 children who underwent surgical closure of a congenital VSD at Aarhus University Hospital, Denmark between 1990 and 1995. After thorough review of all charts, 117 patients were excluded from participation. Exclusion criteria were coexistence of other congenital heart defects (n=89), associated syndromes, e.g. Down's (n=14), operation through a ventricular approach (n=7), missing chart (n=6) and documented arrhythmia requiring pacemaker (n=1). The remaining 68 patients represent a homogeneous group comparing surgeons, anaesthetists, surgical procedure and post-surgical period. A fraction of this group will be randomly selected for this trial, and receives salbutamol or norflouran, blinded.
干预措施: Salbutamol (Drug)
Operated VSD's
Through the use of Electronic Patient Journal (EPJ), the investigators have identified a total of 182 children who underwent surgical closure of a congenital VSD at Aarhus University Hospital, Denmark between 1990 and 1995. After thorough review of all charts, 117 patients were excluded from participation. Exclusion criteria were coexistence of other congenital heart defects (n=89), associated syndromes, e.g. Down's (n=14), operation through a ventricular approach (n=7), missing chart (n=6) and documented arrhythmia requiring pacemaker (n=1). The remaining 68 patients represent a homogeneous group comparing surgeons, anaesthetists, surgical procedure and post-surgical period. A fraction of this group will be randomly selected for this trial, and receives salbutamol or norflouran, blinded.
干预措施: Norflouran (Placebo Evohaler(R) ) (Drug)
Un-operated VSD's
Using EPJ, this project identified a total of 481 children born between 1985 and 1998 who had a small VSD, confirmed through diagnosis codes, that was not closed, neither spontaneously nor surgically. Exclusion criteria were lack of medical record, suffering from coronary disease, other congenital cardiac abnormalities than VSD, spontaneous closure of the ventricular septal defect at inclusion date, magnetic implants, pregnancy, lack of Danish language skills, suffering from lung disease requiring continuous medical treatment. The remaining patients represent a homogenous group of patients with isolated persistent ventricular septal defects. A fraction of this group will be randomly selected for this trial, and receives salbutamol or norflouran, blinded.
干预措施: Salbutamol (Drug)
Un-operated VSD's
Using EPJ, this project identified a total of 481 children born between 1985 and 1998 who had a small VSD, confirmed through diagnosis codes, that was not closed, neither spontaneously nor surgically. Exclusion criteria were lack of medical record, suffering from coronary disease, other congenital cardiac abnormalities than VSD, spontaneous closure of the ventricular septal defect at inclusion date, magnetic implants, pregnancy, lack of Danish language skills, suffering from lung disease requiring continuous medical treatment. The remaining patients represent a homogenous group of patients with isolated persistent ventricular septal defects. A fraction of this group will be randomly selected for this trial, and receives salbutamol or norflouran, blinded.
干预措施: Norflouran (Placebo Evohaler(R) ) (Drug)
Healthy controls
Will function as a control group. Controls will be recruited through www.forsoegsperson.dk and www.sundhed.dk. Current group receives salbutamol or norflouran, blinded.
干预措施: Salbutamol (Drug)
Healthy controls
Will function as a control group. Controls will be recruited through www.forsoegsperson.dk and www.sundhed.dk. Current group receives salbutamol or norflouran, blinded.
干预措施: Norflouran (Placebo Evohaler(R) ) (Drug)
结局指标
主要结局
Peek Exercise Oxygen Uptake (ml O2/kg/min) in VSD-operated patientes
时间窗: 21 to 26 years after surgical closure.
Minute Ventilation (ml/min) in VSD-operated patientes
时间窗: 21 to 26 years after surgical closure.
Maximal workload (W) in VSD-operated patientes.
时间窗: 21 to 26 years after surgical closure.
次要结局
- Airway resistance (R5-R20), in VSD-operated patients.(21 to 26 years after surgical closure.)
- Hear-rate variability, in VSD-operated patients.(21 to 26 years after surgical closure.)
- Peak heart rate at maximal exercise, in VSD-operated patients.(Twentyone to 26 years after surgical closure.)
- Forced expiratory volume in 1 second (FEV1), in VSD-operated patients.(21 to 26 years after surgical closure.)
- Lung clearance index, in VSD-operated patients.(21 to 26 years after surgical closure.)
- Diffusion capacity (DLCO), in VSD-operated patients.(21 to 26 years after surgical closure.)
- Alveolar volume, in VSD-operated patients.(21 to 26 years after surgical closure.)