COVID-19 Treatment Using Methylene Blue and Photodynamic Therapy
Condition: SARS-CoV-2
Study type: Interventional
Phase: Phase 1

Summary: 
      According to the epidemiological situation worldwide and the number of vaccinations made,
      there is little success in the fight against COVID-19. For many reasons, methylene blue is a
      promising drug for an active treatment against SARS-CoV-2 infected patients. Since methylene
      blue can work as a photosensitizer, photodynamic therapy as an antiviral treatment has great
      potential in the treatment of COVID-19. This clinical study investigated the effectiveness of
      SARS-CoV-2 infected people treatment using methylene blue and the following photodynamic
      therapy on the base of the L.L. Levshin Institute of Cluster Oncology (Department of
      Infectious Diseases №13) of I.M. Sechenov First Moscow State Medical University.
    

Detailed description: 
      This is a randomized, parallel, single masking clinical study 60 participants aged 18-90 with
      one positive COVID-19 quantitative Polymerase Chain Reaction test and any severity of
      pneumonia (checked by computer tomography scans) were recruited. The experimental and control
      samples included 30 participants. Randomization was performed using the Random Number Table
      generated in STATISTICA Advanced 13.3. The physiological parameters including oxygen
      saturation, severity of pneumonia using computer tomography scans, heart rate, symptoms, and
      physical examination were collected. Participants in the experimental sample received
      methylthioninium chloride, Methylene Blue (SamaraMedProm, Russia, Registration number:
      MP-001834, 13.09.2012) orally in concentration 1 mg/kg in addition to the current therapy of
      the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium,
      levofloxacin, etc.), if any. After 3 hours, photodynamic therapy of the participant's chest
      by a 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number:
      2009/04648, 26.03.2009) with 18 J/cm^2 energy dose was performed for 50 minutes. If the
      participant is in a critical state, inhalation by 0.2 mg Methylene Blue 10 ml water solution
      and following photodynamic therapy of pharynx and nasal cavity using 650 nm laser source with
      36 J/cm^2 energy dose during 10 minutes were performed. Participants in the control sample
      received only standard medical supportive therapy (e.g., azithromycin, hydroxychloroquine,
      aminodihydrophthalazinedione sodium, levofloxacin, etc.). All next steps were performed for p
      participants from the experimental sample: 12 and 24 hours after photodynamic therapy, blood
      saturation were measured. 2 days after - participants will take a quantitative polymerase
      chain reaction test. 14 days after - computer tomography Aquilion One 640 (Canon Medical
      Systems Corporation, Registration Certificate FSZ 2008/01304, 02.07.2018) scans were
      performed. The participant's status scale (EQ-5D-3L, SHOCS-COVID score, validated) was
      checked on day 84. On 24 and 84 days all participants were checked whether they are alive or
      not by phone call. For participants in the control sample continuous check of blood
      saturation, quantitative Polymerase Chain Reaction tests after 2 and 14 days of treatment,
      and computer tomography scans were performed. The primary outcome of this study is to
      calculate the percentage of participants with negative quantitative Polymerase Chain Reaction
      test on SARS-CoV-2 by 2 days after methylene blue administration and photodynamic therapy.
      Experimental and control samples were comparable in gender, age, and severity of the disease.
      Z-test was used to analyze results on quantitative Polymerase Chain Reaction tests within
      control and experimental samples. For each sample paired Student t-test was used to analyze
      individual saturation changes. Wilcoxon criterion was used for data on severity of pneumonia
      and status scale.
    

Intervention name(s): Methylene Blue and Photodynamic Therapy
Intervention type(s): Drug
Intervention description(s): Treatment group. Methylene blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) 1 mg/kg concentration orally one time were added to the current therapy of the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.), if any, and irradiation of the participant's chest was performed by 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 18 J/cm^2 energy dose.
For critically ill participants: Inhalation by 0.2 mg methylene blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) 10 ml water solution and irradiation of pharynx and nasal cavity by 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 36 J/cm^2 energy dose were performed.
Other intervention name(s): Methylene Blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012), 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009)
Intervention MeSH terms: Methylene Blue
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: COVID-19; photodynamic therapy; methylene blue