A Multicenter, Open-label, Parallel-group, Randomized, Adaptive Trial to Evaluate Local Thermotherapy in Patients With Mild-to-moderate COVID-19, to Prevent Disease Progression
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 274
- 试验地点
- 6
- 主要终点
- Progression of disease (composite outcome)
研究概览
简要总结
The etiological agent of the current pandemic is a (+)ssRNA virus. SARS-CoV-2 is infecting thousands of people in the world with a fatality rate that varies from 0.1 to 5% in affected countries, thereby causing enormous economic losses. Few antibiotics have shown any efficacy in their combat, but have not yet proven adequate to stop the spread of the disease, nor are there any approved vaccines at the moment. From experiments in plants ongoing infections by RNA viruses, using thermotherapy, which is the application of heat at a temperature between 35-43 °C, the investigators know that raising the temperature affects the transcription of viral proteins due to the formation of small RNA molecules that interrupt the replication process by grouping in specific regions of the RNA molecule, preventing and inhibiting transcription. These small molecules are called small interfering RNAs (siRNAs). This feature has been used through thermotherapy in humans to combat the rapid replication of cells (i.e. cancer cells), attack cells infected by RNA viruses, and in the treatment of some parasitic infections.There are various commercially available devices for thermotherapy use in humans; they are mainly being used to ease muscle pain. They work by increasing the temperature in the range recommended for thermotherapy in humans 39-43 ° C. Therefore, the investigators consider this treatment modality can be used to aid in the elimination of SARS-CoV-2 from the human body, decreasing viral load, which could allow the immune system time for its control and elimination.
详细描述
Considering the nature of the causative agent of COVID-19, a (+)ssRNA virus, the investigators propose the use of thermotherapy as a modality for viral containment, thereby preventing the progression of the infection to severe cases. The investigators consider applying the intervention with thermotherapy mainly as an adjuvant therapy in high-risk patients. The most accessible thermotherapy delivery method the investigators have identified is the use of an electric chest pad for its wide and known clinical use, including its recommended use for patients with arthritis. The intensity of temperature delivered by the electric cushion should be placed on the first level (lowest level), to avoid discomfort to the patient. The electric cushion provides a continuous hour of regulated heat, with enough penetration to raise the external temperature of the area to 40-42 ° C, a temperature range at which facilitation of elimination of the virus is expected.
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
- None
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
- •Patient with symptoms of COVID-19 (fever, headache, cough, sore throat, myalgias, arthralgias, shortness of breath, anosmia, fatigue, diarrhea, vomit, or conjunctivitis) meeting criteria for mild or moderate COVID-19 according to the following criteria:
- •Mild COVID-19: With or without mild pneumonia. Peripheral oxygen arterial saturation (SaO2) greater than or equal to 94% (90% in Mexico City and Guadalajara) at room air. Does not meet criteria of moderate, severe, or critical COVID-
- •Moderate COVID-19: Patient with pneumonia and risk factors for disease progression; meeting all the following: Shortness of breath, peripheral oxygen arterial saturation (SaO2) greater than or equal to 94% (90% in Mexico City and Guadalajara) with a maximum 3 L/min of supplementary oxygen, does not meet criteria for severe, or critical COVID-
- •Patient with less than or equal to 5 days from symptom onset
- •Participant understands the intervention and procedures and accepts randomization.
排除标准
- •Suspected or confirmed pregnancy at evaluation
- •Severe decompensation of any of the patient's underlying diseases
- •Previous diagnosis of COVID-19 with complete resolution of symptoms for at least 2 days.
- •Patients meeting criteria for severe or critical COVID-19 at evaluation:
- •Severe COVID-19 - Patient with ≥1 of the following: tachypnea (≥30 breaths per minute), peripheral oxygen arterial saturation (SaO2) less than or equal to 93% (89% in Mexico City and Guadalajara) with a maximum 3 L/min of supplementary oxygen (patients requiring ≥4 L/min will be considered to have progressed to severe COVID-19), or PaO2/FiO2 ratio <
- •Critical COVID-19 - Patient with ARDS, shock, multiorgan failure, or any other condition requiring admission to an intensive care unit.
- •Elimination Criteria:
- •Participant retires consent to participate in the study
- •Patient requiring ≥4 L/min of supplementary oxygen in the 24 hours of hospitalization (in the case that randomization occurred in the first 24 hours of hospitalization)
- •Two negative tests against SARS-CoV-2 (a sequential diagnostic strategy will be implemented to reduce losses due to false negative tests).
- •Patient that do not tolerate thermotherapy and requests to stop receiving the intervention.
- •Transfer to another medical unit in the first 5 days of inclusion in the study.
结局指标
主要结局
Progression of disease (composite outcome)
时间窗: 28 days
Progression to any of the following: 1. Severe COVID-19 - Patient with ≥1 of the following: tachypnea (≥30 breaths per minute), peripheral oxygen arterial saturation (SaO2) less than or equal to 93% (89% in Mexico City and Guadalajara) with a maximum 3 L/min of supplementary oxygen (patients requiring ≥4 L/min will be considered to have progressed to severe COVID-19), or PaO2/FiO2 ratio \<300. 2. Critical COVID-19 - Patient with ARDS, shock, multiorgan failure, or any other condition requiring admission to an intensive care unit. 3. Death
次要结局
- Mortality at day 15(15 days)
- Percentage of participants at each clinical status in the Ordinal Scale at Day 28(28 days)
- Time (days) to last requiring supplementary oxygen according to modality(28 days)
- Mortality at day 28(28 days)
- Time to progression to severe COVID-19(Up to 33 days)
- Time to progression to critical COVID-19(Up to 33 days)
- Hospitalization time(Up to 33 days)
- Percentage of participants at each clinical status in the Ordinal Scale at Day 15(15 days)
- Change in National Early Warning Score 2 (NEWS-2) with respect to baseline(Days 1, 5, 15, and 28)
- Proportion of patients requiring invasive mechanical ventilation(28 days)
- Proportion of patients tolerating the intervention (no comparison)(5 days)
- Proportion of patients requiring admission to intensive care unit (ICU)(28 days)
- Time to requiring invasive mechanical ventilation(Up to 33 days)
- Time to requiring admission to intensive care unit (ICU)(Up to 33 days)
- Proportion of patients with adverse events according to outcome(28 days)
- Proportion of patients with adverse events according to severity(28 days)
- Proportion of patients with adverse events according to causality(28 days)
研究者
Norma del Carmen Galindo-Sevilla
Principal Investigator
Instituto Nacional de Perinatologia