Local Thermotherapy for Patients With Mild-to-moderate COVID-19

COVID-19 Clinical Trial

— TherMoCoV  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04363541
• Other study ID #: U1111-1250-7416
• Status: Recruiting
• Phase: N/A
• Start date: August 27, 2020
• Est. completion date: June 2022

Study information

• Verified date: November 2020
• Source: Instituto Nacional de Perinatologia
• Contact: Norma del Carmen Galindo Sevilla, PhD
• Phone: +525539968217
• Email: ngalindosevilla[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 274
• Est. completion date: June 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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:

1. 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-19.

2. 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-19.

2. Patient with less than or equal to 5 days from symptom onset

3. Participant understands the intervention and procedures and accepts randomization.

Exclusion Criteria:

1. Suspected or confirmed pregnancy at evaluation

2. Severe decompensation of any of the patient's underlying diseases

3. Previous diagnosis of COVID-19 with complete resolution of symptoms for at least 2 days.

4. Patients meeting criteria for severe or critical COVID-19 at evaluation:

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.

Elimination Criteria:

1. Participant retires consent to participate in the study

2. 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)

3. Two negative tests against SARS-CoV-2 (a sequential diagnostic strategy will be implemented to reduce losses due to false negative tests).

4. Patient that do not tolerate thermotherapy and requests to stop receiving the intervention.

5. Transfer to another medical unit in the first 5 days of inclusion in the study.

Related Conditions & MeSH terms

• COVID-19
• Thermotherapy

Intervention

Device:
• Electric pad for human external pain therapy
An electric pad for local heat production will be put on the back of the patient for two hours

Locations

Country	Name	City	State
Mexico	Hospital Dr. Ángel Leaño	Guadalajara	Jalisco
Mexico	Unidad Temporal Movil COVID-19 Autódromo Hermanos Rodríguez IMSS	Mexico City
Mexico	Hospital Regional de Alta Especialidad "Dr. Juan Graham Casasus"	Villahermosa	Tabasco

Sponsors (7)

Lead Sponsor	Collaborator
Instituto Nacional de Perinatologia	Direccion General de Calidad y Educacion en Salud, Hospital Dr. Ángel Leaño, Hospital Regional de Alta Especialidad Juan Graham Tabasco, Instituto Mexicano del Seguro Social, National Polytechnic Institute, Mexico, Universidad Juárez Autónoma de Tabasco

Country where clinical trial is conducted

Mexico, 

References & Publications (3)

Liu J, Zhang X, Zhang F, Hong N, Wang G, Wang A, Wang L. Identification and characterization of microRNAs from in vitro-grown pear shoots infected with Apple stem grooving virus in response to high temperature using small RNA sequencing. BMC Genomics. 2015 Nov 16;16:945. doi: 10.1186/s12864-015-2126-8. — View Citation

Wang MR, Cui ZH, Li JW, Hao XY, Zhao L, Wang QC. In vitro thermotherapy-based methods for plant virus eradication. Plant Methods. 2018 Oct 6;14:87. doi: 10.1186/s13007-018-0355-y. eCollection 2018. Review. — View Citation

Zhu LL, Gao XH, Qi R, Hong Y, Li X, Wang X, McHepange UO, Zhang L, Wei H, Chen HD. Local hyperthermia could induce antiviral activity by endogenous interferon-dependent pathway in condyloma acuminata. Antiviral Res. 2010 Nov;88(2):187-92. doi: 10.1016/j.antiviral.2010.08.012. Epub 2010 Aug 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparison of laboratory parameters with respect to baseline (units: 10^3/microliter)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: total leucocytes, neutrophils, lymphocytes, monocytes, and platelets	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: milligrams/deciliter)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: glucose, urea, blood urea nitrogen, creatinine, total bilirubin, direct bilirubin, and indirect bilirubin.	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: grams/deciliter)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: hemoglobin, and albumin	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: milligrams/liter)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: C-reactive protein	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: nanograms/milliliter)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: D-dimer, and procalcitonin	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: International Units/liter)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK).	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (ratio: no units)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: neutrophil-to-lymphocyte ratio, and international normalized ratio (INR).	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: percent)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: hematocrit	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: seconds)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: prothrombin time (PT), and partial thromboplastin time (PTT)	Days 1, 5, 15, and 28
Other	Comparison of laboratory parameters with respect to baseline (units: millimeters/hour)	Change in laboratory parameters with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; Parameters to be included are: erythrocyte sedimentation rate (ESR)	Days 1, 5, 15, and 28
Other	Comparison of cytokine levels with respect to baseline	Change in cytokine levels with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.	Days 1, 5, 15, and 28
Primary	Progression of disease (composite outcome)	Progression to any of the following: 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.; Critical COVID-19 - Patient with ARDS, shock, multiorgan failure, or any other condition requiring admission to an intensive care unit.; Death	28 days
Secondary	Mortality at day 15	Proportion of participants deceased by day 15 after enrollment	15 days
Secondary	Mortality at day 28	Proportion of participants deceased by day 28 after enrollment	28 days
Secondary	Time to progression to severe COVID-19	Days from symptom onset to progression to severe COVID-19	Up to 33 days
Secondary	Time to progression to critical COVID-19	Days from symptom onset to progression to critical COVID-19	Up to 33 days
Secondary	Hospitalization time	In-hospital stay in days	Up to 33 days
Secondary	Percentage of participants at each clinical status in the Ordinal Scale at Day 15	Ordinal scale of 7 categories: 1) Not hospitalized, without limitations on daily activities; 2) Not hospitalized, with limitations on daily activities; 3) Hospitalized, not requiring supplementary oxygen; 4) Hospitalized, requiring low-flow supplementary oxygen; 5) Hospitalized, requiring supplementary oxygen with high-flow nasal cannula or non-invasive ventilation; 6) Hospitalized, under invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 7) Death	15 days
Secondary	Percentage of participants at each clinical status in the Ordinal Scale at Day 28	Ordinal scale of 7 categories: 1) Not hospitalized, without limitations on daily activities; 2) Not hospitalized, with limitations on daily activities; 3) Hospitalized, not requiring supplementary oxygen; 4) Hospitalized, requiring low-flow supplementary oxygen; 5) Hospitalized, requiring supplementary oxygen with high-flow nasal cannula or non-invasive ventilation; 6) Hospitalized, under invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 7) Death	28 days
Secondary	Time (days) to last requiring supplementary oxygen according to modality	Modalities: 1) Simple nasal cannula or face mask; 2) Face mask with reservoir; 3) High-flow nasal cannula; 4) Non-invasive mechanical ventilation; 5) Invasive mechanical ventilation	28 days
Secondary	Change in National Early Warning Score 2 (NEWS-2) with respect to baseline	Change in the National Early Warning Score 2 (NEWS-2) with respect to baseline (Day 1), measured at day 5 for all patients, and days 15 & 28 only for patients that remain hospitalized.; This score evaluates 7 parameters (respiratory rate, peripheral arterial oxygen saturation, supplementary oxygen requirements, systolic arterial blood pressure, heart rate, consciousness, and body temperature). Assigned values for every parameter may range from 0 to 3 points, except for supplementary oxygen for which possible values are 0 (not requiring supplementary oxygen) and 2 (requiring supplementary oxygen). The total sum of points for this score may range from 0 to 20 points. Higher scores reflect increasing clinical deterioration.	Days 1, 5, 15, and 28
Secondary	Proportion of patients requiring invasive mechanical ventilation	Proportion of patients requiring invasive mechanical ventilation during the entire follow-up period	28 days
Secondary	Proportion of patients requiring admission to intensive care unit (ICU)	Proportion of patients requiring admission to intensive care unit (ICU) during the entire follow-up period	28 days
Secondary	Time to requiring invasive mechanical ventilation	Days from symptom onset to progression to requiring invasive mechanical ventilation	Up to 33 days
Secondary	Time to requiring admission to intensive care unit (ICU)	Days from symptom onset to requiring admission to intensive care unit (ICU)	Up to 33 days
Secondary	Proportion of patients with adverse events according to outcome	Severe: Causes death of the patient, puts the patient's life at risk in the moment of occurrence, requires hospitalization or prolongs hospitalization, causes persistent or significant disability.; Non-severe adverse events: Do not meet the previously outlined criteria.	28 days
Secondary	Proportion of patients with adverse events according to severity	Mild (Grade 1): Present with easily tolerated signs and symptoms, do not need specific treatment, do not prolong hospitalization, nor require suspension of the intervention; Moderate (Grade 2): Interfere with daily activities (school or work), do not directly threaten life, require specific pharmacological treatment, and do not necessarily require suspension of the intervention.; Severe (Grades 3, 4, and 5): Interfere with daily activities (school and work), require pharmacological treatment and suspension of the intervention.	28 days
Secondary	Proportion of patients with adverse events according to causality	Certain; Probable; Possible; Uncertain; Unclassifiable	28 days
Secondary	Proportion of patients tolerating the intervention (no comparison)	Proportion of patients tolerating the intervention (number of sessions and minutes per session).	5 days