Methylene Blue Treatment of COVID-19

Evaluation of the Efficacy of Methylene Blue Administration in SARS-CoV2- Affected Patients: a Phase 2, Randomized, Placebo- Controlled, Single Blind Clinical Trial

Despite enormous progress in understanding COVID-19, there is little evidence that a solution, therapeutic or preventive, is close to being achieved. Repurposing of well known, widely available drugs represent an attractive approach to speed up availability of active treatments. Such substances as i.e. hydroxychloroquine and others, are already under investigation and in widespread off label use. For many reasons Methylene blue (MB), the oldest synthetic substance in medicine (1876 synthesized by BASF) is such a promising candidate for an active treatment against SARS-CoV-2 infected people and for COVID-19 patients.

Study Overview

• Status: Active, not recruiting
• Conditions: SARS-CoV2
• Intervention / Treatment: Drug: Methylene Blue; Drug: Control Test

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Ticino
    • Lugano, Ticino, Switzerland, 6900
      • Fondazione Epatocentro Ticino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria are:

• signed informed consent
• age ≥ 18 years
• microbiologically confirmed SARS-CoV-2 infection
• negative pregnancy test in women of child-bearing age

Exclusion criteria are:

• documented refusal to participate in the study
• known G-6-Phophatase deficiency
• treatment with a serotoninergic drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylene Blue; Methylene Blue 100 mg capsules. Patients will receive Methylene blue (MB) capsules of 100mg every 12 hours for a total of 5 days.	Drug: Methylene Blue; Treatment Group. Methylene Blue 100 mg capsules, twice a day for 5 consecutive days, will be added to the current therapy of the patient, if any.
Active Comparator: control group; The control intervention would be the group receiving 100 mg placebo capsules twice a day for five consecutive days	Drug: Control Test; Arm B: Control Group. Placebo capsules 100 mg twice a day for 5 consecutive days, will be added to the current therapy of the patient, if any.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to compare the viral load kinetics in the enrolled patients with a SARS-CoV-2 positive nasopharyngeal swab demonstrating a reduction of the area under the curve day 0- day 21 of at least 25%	As primary outcome we will measure the viral load kinetics in the enrolled patients. This means the viral load (expressed as cycled of replication with the PCR method and the number of RNA copies) at baseline and at each scheduled timepoint of the study	day 0 - day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To calculate the percentage of patients clearing SARS-CoV-2 by 3, 6, 9, 12, 15 and 21 days after diagnosis	We report the number of patients (expressed as percentage) with negative oro-pharyngeal swab at the scheduled time-points	3, 6, 9, 12, 15 and 21 days after diagnosis
To calculate the percentage of patients having a reduction of viral load of > 2 log by day 3	We calculate the number of patients (expressed as percentage) that have a decreased viral load (expressed as RNA copies) greater than 2 log by day three	day 3
To calculate the percentage of patients having a poor outcome as measured by the need of hospitalization for COVID-19	We calculate the number of patients (expressed as percentage) that need hospitalization due to COVID-19, within the timeframe of the study	3, 6, 9, 12, 15, 21, 28 and 84 days after diagnosis
To calculate the percentage of patients alive	We calculate the number of patients (expressed as percentage) still alive at day 28 and 84 of samples collection	at 28-days and 84-days
Safety and tolerability of the administered drug are registered as "adverse events", which are all symptoms related or supposed to be related to the drug that appeared after the drug intake and were NOT present at baseline or before	Safety and tolerability of the administered drug are registered as "adverse events", which are all symptoms related or supposed to be related to the drug that appeared after the drug intake and were NOT present at baseline or before Adverse events are expressed as present (1) or absent (0), in the dedicated data sheet which will be collected at each scheduled visit	3, 6, 9, 12, 15, 21, 28 and 84 days after diagnosis
To measure the compliance by calculating the number of capsules taken by the patient and the overall number of patients who complete the treatment	We calculate the number of pills (expressed as absolute number) taken by each enrolled patient during the study	3, 6, 9, 12, 15 and 21 days after diagnosis

Collaborators and Investigators

• Sponsor: Fondazione Epatocentro Ticino

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: MB treatment of COVID19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No