Photobiomodulation Therapy Combined With Static Magnetic Field in Patients With COVID-19

• ClinicalTrials.gov Identifier: NCT04386694
• Recruitment Status: Completed
• First Posted: May 13, 2020
• Last Update Posted: October 29, 2020
• Sponsor: University of Nove de Julho
• Collaborator: Hospital Tacchini/RS
• Information provided by (Responsible Party): Ernesto Cesar Pinto Leal Junior, University of Nove de Julho

Tracking Information

• First Submitted Date: May 8, 2020
• First Posted Date: May 13, 2020
• Last Update Posted Date: October 29, 2020
• Actual Study Start Date: May 18, 2020
• Actual Primary Completion Date: September 17, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 11, 2020)

Time until discharge [ Time Frame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 20 days. ]

Number of days hospitalized in the ICU until discharge or death.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 9, 2020)

• Survival rate [ Time Frame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 20 days. ]
  Rate of how many people survived and were discharged and how many died.
• Diaphragm muscle function [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Diaphragm thickness will be measured by ultrasound.
• Platelet count [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Platelet count will be measured by blood test.
• Leukogram [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Leukogram will be measured by blood test.
• Erythrogram [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Erythrogram will be measured by blood test.
• C-reactive protein [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  C-reactive protein will be measured by blood test.
• D-dimer [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  D-dimer will be measured by blood test.
• Immunoglobulin G [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Immunoglobulin G will be measured by blood test.
• Immunoglobulin M [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Immunoglobulin M will be measured by blood test.
• Levels of positive end-expiratory pressure (PEEP) [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  The levels of PEEP will be measured using a mechanical ventilator.
• Fraction of inspired oxygen (FiO2) [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  The levels of FiO2 will be measured using a mechanical ventilator.
• Arterial partial pressure of oxygen (PO2) [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  PO2 will be measured by arterial blood gas analysis.
• Arterial partial pressure of oxygen (PO2)/Fraction of inspired oxygen (FiO2) ratio [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  PO2/FiO2 ratio will be measured by arterial blood gas analysis.
• Levels of tumor necrosis factor-α (TNF-α) [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Levels of TNF-α will be measured by blood test.
• Levels of vitamin D [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Levels of vitamin D will be measured by blood test.

Original Secondary Outcome Measures (submitted: May 11, 2020)

• Survival rate [ Time Frame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 20 days. ]
  Rate of how many people survived and were discharged and how many died.
• Diaphragm muscle function [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Diaphragm thickness will be measured by ultrasound.
• Platelet count [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Platelet count will be measured by blood test.
• Leukogram [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Leukogram will be measured by blood test.
• Erythrogram [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Erythrogram will be measured by blood test.
• C-reactive protein [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  C-reactive protein will be measured by blood test.
• D-dimer [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  D-dimer will be measured by blood test.
• Immunoglobulin G [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Immunoglobulin G will be measured by blood test.
• Immunoglobulin M [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Immunoglobulin M will be measured by blood test.
• Th1 cells [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Th1 cells will be measured by blood test.
• Th2 cells [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  Th2 cells will be measured by blood test.
• Levels of positive end-expiratory pressure (PEEP) [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  The levels of PEEP will be measured using a mechanical ventilator.
• Fraction of inspired oxygen (FiO2) [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  The levels of FiO2 will be measured using a mechanical ventilator.
• Arterial partial pressure of oxygen (PO2) [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  PO2 will be measured by arterial blood gas analysis.
• Arterial partial pressure of oxygen (PO2)/Fraction of inspired oxygen (FiO2) ratio [ Time Frame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days. ]
  PO2/FiO2 ratio will be measured by arterial blood gas analysis.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Photobiomodulation Therapy Combined With Static Magnetic Field in Patients With COVID-19
• Official Title: Is Photobiomodulation Therapy (PBMT) Combined With Static Magnetic Field (sMF) Able to Decrease the Intensive Care Unit (ICU) Length of Stay for Patients With COVID-19?

Brief Summary

Coronavirus disease 2019 (COVID-19) is a disease caused by a novel coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The most characteristic symptom of patients with COVID-19 is respiratory distress, leading to inability to sustain spontaneous breathing. In addition, patients with COVID-19 have dyspnea and respiratory muscle fatigue. Therefore, it is necessary to use strategies that minimize the impact of COVID-19 on the respiratory muscles, accelerating the ventilatory weaning process and optimizing the functional capacity of the involved muscles.

Over the past years, evidence has shown the effectivity of photobiomodulation therapy (PBMT) combined with static magnetic field (sMF) (PBMT/sMF) in delaying muscle fatigue, decrease in markers of inflammatory damage and oxidative stress of skeletal muscle. These effects result in an improvement in the functional capacity of the irradiated muscles by PBMT/sMF. However, do date, there is a lack of evidence regarding the effects of PBMT/sMF on the respiratory muscles.

Therefore, the irradiation of PBMT/sMF may result in improvement in the functional capacity of respiratory muscles in patients with COVID-19, accelerating the ventilatory weaning process of the patients intubated due to respiratory failure. In addition, the irradiation of PBMT/sMF may induce the increase of anti-inflammatory mediators' activity in patients with COVID-19.

Thus, the aim of this project is to investigate the effects of PBMT/sMF on respiratory muscles of patients admitted to the Intensive Care Unit (ICU) with COVID-19 using invasive mechanical ventilation.

Detailed Description

To achieve the proposed objectives it will be performed a randomized, triple-blind, placebo-controlled trial, with patients admitted to the adult ICU with COVID-19 using invasive mechanical ventilation due to respiratory failure. The patients will be randomly allocated to two treatment groups: 1. Active PBMT/sMF (MR5™ ACTIV PRO LaserShower) or Placebo PBMT/sMF (MR5™ ACTIV PRO LaserShower). The patients will be treated by a blinded therapist, and the patients will be blinded to the treatment received.

Since there are no studies in this field, initially it will be randomized 30 patients (15 patients per group) to determine the final sample size for this study.

The patients randomly allocated to the two groups will be subjected to treatment once a day, during the ICU stay, until discharge or death.

All data will be collected by a blinded assessor. The investigators will analyze:

1. Number of days hospitalized in the ICU until discharge or death.
2. Survival rate: rate of how many people survived and were discharged and how many died.
3. Muscular function of the diaphragm: the first assessment will be performed within 24 hours after the patient's intubation, the second 10 days after the first, and the third at the pre-discharge from the ICU.
4. Blood tests: baseline (admission to the ICU), 10 days after the admission, and endpoint (discharge or death).
5. Mechanical ventilation control parameters: baseline (admission to the ICU), 10 days after the admission, and endpoint (discharge or death).
6. Arterial Blood Gas Analysis: baseline (admission to the ICU), 10 days after the admission, and endpoint (discharge or death).

The data regarding the blood tests and arterial blood gas analysis will be collected directly from electronic medical record of each patients, since it is a daily hospital routine to perform these blood tests. The data will be collected by two assessors blinded to the treatment applied. The mechanical ventilation control parameters will be collected directly in the mechanical ventilator.

Statistical analysis: All the data will be analyzed by a blinded researcher not involved in data collection. The findings will be tested for their normality using the Kolmogorov-Smirnov test. Parametric data will be expressed as mean and standard deviation and non-parametric data as median and respective upper and lower limits, data can be also expressed as frequency (%). Parametric data will be analysed by two-way repeated measures analysis of variance (time vs experimental group) with post hoc Bonferroni correction. Non-parametric data will be analysed using the Friedman test and, secondarily, the Wilcoxon signed-rank test. The association between categorical variables will be analyzed using the Chi-square test or Fisher's exact test. The significance level will be set at p<0.05.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

A researcher will program the device (PMBT/sMF or placebo) and will be instructed not to inform the patients or other researchers as to the type of treatment (PMBT/sMF or placebo). Therefore, the therapist responsible for the treatment, the investigators and the outcome assessors will be blinded to the type of treatment being administered to the patients. The sounds and signals emitted from the device as well as the information displayed on the screen will be identical, regardless of the type of treatment (PBMT/sMF or placebo).

Primary Purpose: Treatment

Condition

• COVID-19
• Respiratory Failure

Intervention

• Device: Active PBMT/sMF
  The PBMT/sMF will be irradiated in the lower thorax and neck areas, with the patients in supine position. PBMT/sMF application time will be 60 seconds per site. The dose used in the lower thorax will be 31.50 J per site, a total of 6 sites will be irradiated, totalizing a dose of 189J. In addition, the dose used in the neck area (bilaterally) will be 31.50J per site, a total of 1 site (bilaterally) will be irradiated, totalizing a dose of 31.50J (bilaterally). PBMT/sMF will be applied using the direct contact method with light pressure on the skin.
• Device: Placebo PBMT/sMF
  The placebo PBMT/sMF will be irradiated in the lower thorax and neck areas, with the patients in supine position. PBMT/sMF application time will be 60 seconds per site. The dose used for applications during the treatment will be 0 Joules (J) per site. The sounds and signals emitted from the device as well as the information displayed on the screen will be identical, regardless of the type of treatment (active or placebo). PBMT/sMF will be applied using the direct contact method with light pressure on the skin.

Study Arms

• Experimental: PBMT/sMF

  Active PBMT/sMF will be applied once a day, during the ICU stay, until discharge or death. The patients will receive standard physical therapy care associated with PBMT/sMF.

  PBMT/sMF will be applied using MR5™ ACTIV PRO LaserShower, manufactured by Multi Radiance Medical (Solon, OH, USA). This device has 4 diodes of 905 nm (1.25 mW each diode, 0.32 cm2 each), 8 diodes of 633 nm (25 mW each diode, 0.85 cm2 - each), and 8 diodes of 850 nm (40 mW each diode, 0.56 cm2 - each). The static magnetic field is 110 mT.

  Intervention: Device: Active PBMT/sMF
• Placebo Comparator: Placebo PBMT/sMF

  Placebo PBMT/sMF will be applied once a day, during the ICU stay, until discharge or death. The patients will receive standard physical therapy care associated with placebo PBMT/sMF.

  The placebo PBMT will be applied using MR5™ ACTIV PRO LaserShower Laser Therapy System, manufactured by Multi Radiance Medical (Solon, OH, USA). The ACTIV PRO emits 905nm, and 850nm via an electric diode energy source with outputs to 0%. The static magnetic field will be also turned off. The 660nm light via an electric diode energy source with outputs to >1% to appear like the active comparator.

  Intervention: Device: Placebo PBMT/sMF

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 11, 2020): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 17, 2020
• Actual Primary Completion Date: September 17, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients admitted to the adult Intensive Care Unit with Covid-19 infection;
• Need for orotracheal intubation;
• Invasive mechanical ventilation due to respiratory failure.

Exclusion Criteria:

• Suspected patients who had a negative result of the diagnostic examination for COVID-19 infection;
• Patients positioned in pronation for more than 24 hours;
• Cancer patients;
• Pregnancy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT04386694
• Other Study ID Numbers: 3.985.226
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Responsible Party: Ernesto Cesar Pinto Leal Junior, University of Nove de Julho
• Study Sponsor: University of Nove de Julho
• Collaborators: Hospital Tacchini/RS
• Investigators: Not Provided
• PRS Account: University of Nove de Julho
• Verification Date: October 2020