Methylene Blue Treatment of COVID-19

Study Overview
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Brief Summary
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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.

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

Conditions
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SARS-CoV2

Intervention / Treatment
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* Drug: Methylene Blue
* Drug: Control Test


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a phase 2 proof of concept, randomized, placebo controlled, single blind clinical trial on the efficacy of Methylene Blue against SARS-CoV-2 infection in patients with recently diagnosed SARS-CoV-2 infection
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylene Blue<br>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<br>* 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.<br>|
| Active Comparator: control group<br>The control intervention would be the group receiving 100 mg placebo capsules twice a day for five consecutive days | Drug: Control Test<br>* 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.<br>|

What is the study measuring?
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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 |