Evaluation of the Daily Intake of 0.5 L of Water Saturated With Molecular Hydrogen for 21 Days in COVID-19 Patients Treated in Ambulatory Care. Double-blind, Randomized, Comparative Study
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 700
- 试验地点
- 5
- 主要终点
- Change in the incidence rate of the onset of clinical worsening
研究概览
简要总结
Through its anti-inflammatory role, molecular hydrogen could have a beneficial effect in preventing the runaway inflammatory reactions that lead to complications of Covid-19.
This hypothesis is supported by numerous preclinical and theoretical arguments, as well as by some Chinese clinical studies (the Chinese guidelines for the management of Covid-19 recommend the inhalation of hydrogen), a recommendation whose interest has just been confirmed by a publication describing the very positive results of a clinical study in China.
Through its anti-inflammatory role, molecular hydrogen could have a beneficial effect in preventing the runaway inflammatory reactions that lead to complications of Covid-19.
The ingestion of water saturated with molecular hydrogen has been the subject of several clinical studies in other indications than Covid-19, and no side effects of this ingestion have been reported. A recent publication recommends initiating clinical trials using a hydrogen fortified beverage.
详细描述
CURRENT STATE OF KNOWLEDGE ON PATHOLOGY :
SARS-CoV-2 is the causative agent of a new infectious respiratory disease called Covid-19 (for CoronaVirus Disease 2019) which is characterized primarily by potentially serious and fatal lung damage. The seriousness of the clinical signs associated with this pathology requires hospital admission of approximately 20% of patients, of which 5 to 10% will be admitted to intensive care. The more severe forms, though seen mainly in people over 60 years old, also occur in younger patients, most of whom are affected by comorbidities such as hypertension (30%), diabetes (17 %) or cardiovascular pathologies (15%). The mortality due to this infection varies according to the series between 2 and 14%. The most severe cases of this pathology begin with dyspnea which rapidly worsens around the 7th to 10th day of the disease into Acute Respiratory Distress Syndrome (ARDS) which requires the patient to be mechanically ventilated in the intensive care unit. and is responsible for the majority of deaths. ARDS is an active feature of severe forms of Sars-Cov-2 infection, directly linked to the mortality of this infection. The clinico-radiological aspect is not specific to other aetiologies of ARDS. Certain biological parameters suggest a massive and sudden release of cytokines (interleukins IL-6, IL-8 and IL-10 mainly) secondary to a syndrome of macrophage activation mainly at the pulmonary level. This cytokine storm is comparable to that of secondary hemophagocytic lymphohistiocytosis which occurs in approximately 4% of sepsis and is accompanied, in 50% of cases, by ARDS. The effect of this inflammatory cascade leads to an uncontrolled influx and activation of polynuclear and macrophagic cells with hyperproduction of oxygen-derived free radicals. These reactive species will damage the capillary alveolar membrane with initially hyperpermeability, and secondarily with fibrosis and fibroblast proliferation.
Several therapeutic trials aimed at reducing or controlling this immune storm are underway (anti-IL-6 antibodies, anti-r IL6 antibodies, corticosteroids).
PROPOSED STRATEGY, PURPOSE AND NOVELTY OF THE STUDY :
There are many theoretical, preclinical and clinical arguments to suggest that the administration of molecular hydrogen (H2) could, by the original anti-inflammatory effect of H2, help to avoid the cytokine storm. These arguments justified the launch of clinical trials proposing the inhalation of H2 (the investigators submitted to the French Ministry of Health (ANSM) a protocol, which has just been accepted by the ANSM, providing for the inhalation of H2 in patients Covid-19 at the start of oxygen therapy). As will be described in the next section, inhalation delivers significantly more H2 than ingestion of water saturated with H2. However, the inhalation of H2 involves a complex intervention, which in practice can only be considered late, as it can only be implemented for the benefit of hospitalized patients, typically in addition to oxygen therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
They will be labeled study (randomization number to respect blind and legal notices labeling clinical research).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 59 years old or over 60 years old.
- •If patient 18 to 59 years old, presence of at least one risk factor :
- •Hypertension under treatment (all stages)
- •Obesity (BMI ≥30 kg / m2)
- •Diabetes under treatment (all types)
- •Stable ischemic heart disease (all stages)
- •Atrial fibrillation
- •Stable heart failure (all stages)
- •History of stroke
- •Stage 3 chronic renal failure (30 ≤ estimated GFR <60 mL / min / 1.73 m²)
- •COPD (all stages, including chronic respiratory failure under long-term oxygen therapy)
- •Solid tumors or malignant hemopathies that are progressive or whose diagnosis is less than 5 years old
- •Immunodeficiency:
- •of therapeutic origin (solid organ transplantation or transplant of hematopoietic stem cells, anticancer chemotherapy, immunosuppressive treatment, corticosteroid therapy> 15 mg / day equivalent to prednisone price for at least 2 months);
- •or HIV infection and last known CD4 count <200 / mm3
- •History of pulmonary embolism and / or proximal deep vein thrombosis
- •Asthma under inhaled corticosteroid therapy
- •Paired sleep apnea syndrome
- •Peripheral arterial disease of the lower limbs stage II and above
- •Another risk factor presented, according to the list defined by the French High Council of Public Health
- •OR Presence of at least 3 comorbidities, according to the Rapid Responses to COVID-19 from the French High Council of Public Health.
- •Patient with nasopharyngeal swab (antigenic test, RT-PCR, or other HAS-validated swabs to come) :
- •In case of positive test (antigenic test, RT-PCR, Other), patient with at least 1 symptom at the time of testing:
- •In case of negative antigenic or other test or ongoing or uninterpretable RT-PCR test, the patient must present at least 3 of the 11 symptoms of COVID-19 dating back no more than 4 days as defined below and notion of contact (with a certain or probable COVID+ patient) dating back less than 10 days:
- •Fever > 37,5°C since 3 days Cough Sore throat/cold Headache Anosmia, dysgeusia Myalgias, arthralgias, bone pain Respiratory difficulties (feeling of dyspnea at rest) Chest pain (sternal) Digestive complaints (diarrhea, nausea, vomiting) Tachycardia (palpitation) Conjunctivitis (red eyes)
- •No seriousness signs during the consultation and for at least 72 hours.
- •Patient able to understand the procedure and follow it and have tools for a video-consultation.
- •Affiliation to the social security system.
- •Voluntary to participate to the study, informed consent form signed after appropriate information
排除标准
- •The absence of attending or referring physician
- •Any sign of seriousness incompatible with home care.
- •Severe chronic kidney failure or dialysis (i.e. DFGe <30).
- •drink cure Contraindication (500 ml/d for 21 days).
- •Contraindication to any drug in the study, including a known allergy, especially magnesium.
- •Uncontrolled and clinically significant heart disease, whether its origin (arrhythmias, angina, uncompensated congestive heart failure).
- •Subject participating to an other clinical study interventional.
- •Person deprived of liberty or under legal guardianship.
- •No one in the same household who participated in this study.
- •Patient refusing hospitalization.
- •Persons subject to sections L1121-7 and L1121-8 of the CSP (minor, person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure) or not able to communicate his consent verbally.
结局指标
主要结局
Change in the incidence rate of the onset of clinical worsening
时间窗: 12 to 14 days
Demonstrate that the daily ingestion of 250 mL twice a day, i.e. 0.5 L of water saturated with molecular hydrogen for 21 days compared to water not enriched in hydrogen, decreases the incidence rate of the appearance of clinical worsening in patients within 12 to 14 days following a COVID-19 + diagnosis with outpatient care. The primary endpoint is a composite endpoint combining worsening of dyspnea, fatigue, putting on 02, hospitalizations, death occurring within 12 to 14 days of inclusion in the study. The worsening of dyspnea, fatigue being defined as an increase of 25% via Chalder scale for fatigue, MMRC scale for dyspnea. Chalder scale with 11 items (mental 7 questions yes/no and physical symptoms 4 questions yes/no) MMRC scale with 4 stades (stade 0 "no dyspnea" to 4 "strong dyspnea")
次要结局
- Assessment of medium-long term fatigue symptoms(30 Days, 3 months, 12 months)
- Assesment of sleep quality(30 days, 3 months, 12 months)
- Assessment of care consumption(30 days, 3 months, 12 months)
- Assessment of pain(14 days, 30 days, 3 months, 12 months)
- Assessment of oximetry symptoms(30 Days)
- Assessment of quality of life(30 days, 3 months, 12 months)
- Assessment of tolerance(30 days)
- Assessment of compliance(21 days)
- Assessment of medium-long term dyspnea symptoms(30 Days, 3 months, 12 months)
- Assessment of COVID-19 contact cases(30 days)
- Assessment of blind treatment(30 days)
- Assessment of risk factors(30 days, 3 months, 12 months)
- Analysis of older patients(inclusion)