Methylene Blue Treatment of COVID-19

• ClinicalTrials.gov Identifier: NCT04635605
• Recruitment Status: Active, not recruiting
• First Posted: November 19, 2020
• Last Update Posted: April 20, 2022
• Sponsor: Fondazione Epatocentro Ticino
• Information provided by (Responsible Party): Fondazione Epatocentro Ticino

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
SARS-CoV2	Drug: Methylene Blue; Drug: Control Test	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Efficacy of Methylene Blue Administration in SARS-CoV2- Affected Patients: a Phase 2, Randomized, Placebo- Controlled, Single Blind Clinical Trial
• Actual Study Start Date: November 5, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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% [ Time Frame: day 0 - day 21 ]
   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

Secondary Outcome Measures :

1. To calculate the percentage of patients clearing SARS-CoV-2 by 3, 6, 9, 12, 15 and 21 days after diagnosis [ Time Frame: 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
2. To calculate the percentage of patients having a reduction of viral load of > 2 log by day 3 [ Time Frame: 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
3. To calculate the percentage of patients having a poor outcome as measured by the need of hospitalization for COVID-19 [ Time Frame: 3, 6, 9, 12, 15, 21, 28 and 84 days after diagnosis ]
   We calculate the number of patients (expressed as percentage) that need hospitalization due to COVID-19, within the timeframe of the study
4. To calculate the percentage of patients alive [ Time Frame: at 28-days and 84-days ]
   We calculate the number of patients (expressed as percentage) still alive at day 28 and 84 of samples collection
5. 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 [ Time Frame: 3, 6, 9, 12, 15, 21, 28 and 84 days after diagnosis ]
   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
6. To measure the compliance by calculating the number of capsules taken by the patient and the overall number of patients who complete the treatment [ Time Frame: 3, 6, 9, 12, 15 and 21 days after diagnosis ]
   We calculate the number of pills (expressed as absolute number) taken by each enrolled patient during the study

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Switzerland

Fondazione Epatocentro Ticino

Lugano, Ticino, Switzerland, 6900

Sponsors and Collaborators

Fondazione Epatocentro Ticino

More Information

• Responsible Party: Fondazione Epatocentro Ticino
• ClinicalTrials.gov Identifier: NCT04635605
• Other Study ID Numbers: MB treatment of COVID19
• First Posted: November 19, 2020
• Last Update Posted: April 20, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Methylene Blue; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action