Clinical trial NCT04386694: 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?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Respiratory Failure
Keywords: Photobiomodulation Therapy
Static Magnetic Fields
Low-Level Laser Therapy
COVID-19
Invasive Mechanical Ventilation
Respiratory Muscles
Intensive Care United
Lead sponsor: University of Nove de Julho
Sponsor class: OTHER
Collaborators: name: Hospital Tacchini/RS
First posted: 2020-05-13
Enrollment: 30
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time until discharge
timeFrame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 20 days.
Secondary outcomes:
measure: Survival rate
timeFrame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 20 days.
measure: Diaphragm muscle function
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Platelet count
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Leukogram
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Erythrogram
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: C-reactive protein
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: D-dimer
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Immunoglobulin G
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Immunoglobulin M
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Levels of positive end-expiratory pressure (PEEP)
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Fraction of inspired oxygen (FiO2)
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Arterial partial pressure of oxygen (PO2)
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Arterial partial pressure of oxygen (PO2)/Fraction of inspired oxygen (FiO2) ratio
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Levels of tumor necrosis factor-α (TNF-α)
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
measure: Levels of vitamin D
timeFrame: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.
Other outcomes:
Locations:
city: Bento Gonçalves
country: Brazil
facility: Hospital Tacchini
state: RS
Study officials:
References:
citation: De Marchi T, Francio F, Ferlito JV, Weigert R, de Oliveira C, Merlo AP, Pandini DL, Pasqual-Junior BA, Giovanella D, Tomazoni SS, Leal-Junior EC. Effects of Photobiomodulation Therapy Combined with Static Magnetic Field in Severe COVID-19 Patients Requiring Intubation: A Pragmatic Randomized Placebo-Controlled Trial. J Inflamm Res. 2021 Jul 24;14:3569-3585. doi: 10.2147/JIR.S318758. eCollection 2021.