Effectiveness and Cost-effectiveness of Ozone Therapy in Patients With Ischemic Heart Disease Refractory to Medical and Surgical Treatment: Randomized, Triple-blind Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at the end of ozone therapy)
研究概览
简要总结
The main objective of this clinical trial is to evaluate the effectiveness and cost-effectiveness of adding ozone therapy to standard management of patients with advanced ischemic heart disease refractory to medical and surgical treatment.
详细描述
This study will evaluate the potential role of ozone therapy added to the standard management of patients with symptomatic refractory ischemic heart disease, III-IV functional class of the classification of the New York Heart Association (NYHA).
MAIN OBJECTIVES: 1) to evaluate clinical effect and quality of life related to health (HRQOL) of adding O3 to the standard treatment of these patients. 2) to estimate the additional costs of adding O3 to the standard treatment and to evaluate the cost-effectiveness ratio.
SECONDARY OBJECTIVES: 3) To evaluate the evolution of a) biochemical parameters; b) cardiovascular parameters; c) toxicity of O3. 4) Develop and evaluate the acceptability of a shared decision-making (SDM) tool between professionals and patients.
METHODOLOGY: Phase II-III clinical trial, randomized, triple-blind. Sample size: 18 patients.
TREATMENT: All patients will receive their standard treatment + 40 sessions of rectal insufflation:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Masking of: patients, cardiologist and cardiac surgeons (clinical assessment), investigators obtaining other parameters (quality of life, biochemical and clinical parameters), investigators for statistical analysis
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults with ischemic heart disease, Functional Class III-IV from the NYHA, with symptoms in spite of maximal conventional medical treatment and no suitable to further percutaneous or surgical procedures.
- •It should be required clinical diagnosis by the Cardiology Department and confirmation by cardiac catheterization with coronary angiography.
- •Ejection Fraction < 40%
- •Patients who have signed and dated the study 's specific informed consent.
- •Before enrollment, women of childbearing potential should obtain a negative result in the serum or urine pregnancy test at the screening visit, and accept the use of appropriate contraceptive methods at least from the 14 days prior to the first dose of the study drug. up to 14 days after the last one.
排除标准
- •Age < 18 or > 85 years old.
- •Severe valve disease and/or dynamic left ventricular outflow tract obstruction.
- •Pregnancy at the time of enrollment.
- •Limited walking ability due to neurologic or orthopedic impairments of the legs
- •Those who are incapable to fill in the scales used to measure the quality of life variables
- •Cerebral vascular accident (CVA or Transient Ischemic Attack (TIA) within the previous 3 months or carotid stenosis > 80%.
- •Acute myocardial infarction (AMI), Percutaneous coronary intervention (PCI) or transmyocardial laser revascularization (TMR or PMR) within the previous 3 months.
- •Hemodynamically or clinically unstable patients.
- •Severe or limiting pulmonary diseases.
- •Specific liver enzymes [Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) > 5 times the upper limit of normal
- •Increased creatinine > 3 times the upper limit of normal or Glomerular Filtration Rate (GFR) < 25 ml/min or who are on chronic renal dialysis.
- •Severe peripheral vascular disease with rest pain or significant chronic wounds.
- •Uncontrolled cancer disease or severe active systemic infection or HIV.
- •Life expectancy < 4 months
- •Contraindication or disability for rectal ozone administration or to attend scheduled treatments.
- •Known allergy to ozone.
- •Patients who do not meet all the inclusion criteria.
研究组 & 干预措施
Ozone Group:
Standard treatment + Ozone therapy (O3/O2)
干预措施: Ozone (Drug)
Control Group:
Standard treatment + Oxygen (O2)
干预措施: Oxygen (Drug)
结局指标
主要结局
Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at the end of ozone therapy)
时间窗: 16 weeks
Self-reported evaluation of 21 physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each item is scored from 0 (no affected) to 5 (very much affected). Total range from 0 (best) to 105 (worst)
Direct Hospital Cost (at the end of ozone therapy)
时间窗: 16 weeks
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros).
次要结局
- Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at the end of ozone therapy)(16 weeks)
- Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36) questionnaire (at the end of ozone therapy)(16 weeks)
- Change from Baseline in Biochemical parameters of inflammation (at the end of ozone therapy)(16 weeks)
- Change from Baseline in lower limb blood flow by Doppler ultrasound (at the end of ozone therapy)(16 weeks)
- Change from Baseline in Biochemical cardiac parameters (High sensitive troponin, pro-brain natriuretic peptide (proBNP)) (at the end of ozone therapy)(16 weeks)
- Change from Baseline in Six-minute walk test (6MWT) (at the end of ozone therapy)(16 weeks)
- Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at 32 weeks)(32 weeks)
- Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at the end of ozone therapy)(16 weeks)
- Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)(16 weeks)
- Change from Baseline in Montreal Cognitive Assessment (MOCA) questionnaire (at the end of ozone therapy)(16 weeks)
- Change from Baseline in cerebral blood flow by Transcranial doppler (at the end of ozone therapy)(16 weeks)
- Change from Baseline in Hyperspectral image of lower limbs (at the end of ozone therapy)(16 weeks)
- Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at 32 weeks)(32 weeks)
- Direct Hospital Cost (at 32 weeks)(32 weeks)
- Change from Baseline in Montreal Cognitive Assessment (MOCA) questionnaire (at 32 weeks)(32 weeks)
- Change from Baseline (by Echocardiograpy) of: left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) (at 32 weeks)(32 weeks)
- Change from Baseline in Hyperspectral image of lower limbs (at 32 weeks)(32 weeks)
- Change from Baseline (by Echocardiograpy) of: left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) (at the end of ozone therapy)(16 weeks)
- Change from Baseline (by Echocardiograpy) of left ventricular ejection fraction (LVEF) (at the end of ozone therapy)(16 weeks)
- Change from Baseline in Hyperspectral image of the supraciliary area (at the end of ozone therapy)(16 weeks)
- Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36) questionnaire (at 32 weeks)(32 weeks)
- Change from Baseline in Biochemical parameters of inflammation (at 32 weeks)(32 weeks)
- Change from Baseline in lower limb blood flow by Doppler ultrasound (at 32 weeks)(32 weeks)
- Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at 32 weeks)(32 weeks)
- Change from Baseline (by Echocardiograpy) of left ventricular ejection fraction (LVEF) (at 32 weeks)(32 weeks)
- Change from Baseline in cerebral blood flow by Transcranial doppler (at 32 weeks)(32 weeks)
- Change from Baseline in Hyperspectral image of the supraciliary area (at 32 weeks)(32 weeks)
- Change from Baseline in Biochemical cardiac parameters (High sensitive troponin, pro-brain natriuretic peptide (proBNP)) (at 32 weeks)(32 weeks)
- Change from Baseline in Biochemical parameters of oxidative stress (at 32 weeks)(32 weeks)
- Change from Baseline in Six-minute walk test (6MWT) (at 32 weeks)(32 weeks)
研究者
Bernardino Clavo, MD, PhD
MD, PhD, Head of Research Unit
Dr. Negrin University Hospital