COVID-19 Methylene Blue Antiviral Treatment (COMBAT)

Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences

Status and phase: Completed; Phase 2

Conditions: Covid19

Treatments: Drug: Methylene Blue; Drug: Saline nasal spray

Study type: Interventional

Funder types: Other

Identifiers

NCT05004805

COMBAT

Details and patient eligibility

About

This is a pilot study of a single-center, blind, randomized, placebo-controlled, parallel-group study testing for the efficacy and safety of Methylene blue when administered topically as a 0.02% solution for nasopharyngeal and oropharyngeal irrigation in COVID-19 patients requiring hospitalization.

Full description

Purpose of the study. To test the hypothesis that the topical application of 0.02% MB solution in the form of repeated nasopharyngeal irrigation will lead to an accelerated recovery compared to placebo, defined by the clinical, laboratory, and radiological improvement with a negative molecular test for SARS-CoV-2 by polymerase chain reaction (PCR). The main objective of the study is to demonstrate the effectiveness of 0.02% MB irrigation of the nasopharynx mucosa over placebo, alongside the standard treatment carried out in accordance with the Temporary Guidelines of "Prevention, Diagnosis, and Treatment of Novel Coronavirus Infection (COVID-19)", version 11 (May 7, 2021). Regarding the recovery of patients with COVID-19, this is defined as a negative PCR test result for the SARS-CoV-2 coronavirus in swabs from the nasopharynx and oropharynx on the 14th and 28th day after initiation of the experimental treatment.

A secondary objective of this study is to evaluate the additional efficacy and overall safety parameters, including saturation dynamics, C-reactive protein, D-dimer, CT signs of lung damage, dynamics of the National Early Warning Score (NEWS) 2 during treatment. Due to the pilot nature of this study, another goal is to calculate the effect based on the number of subjects per group for a future study.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Men and women aged 18 and over at the time of signing the informed consent.
2. The patient is willing and able to give written informed consent to participate in the study and follow the procedures specified in the protocol.
3. Diagnosed with COVID-19, confirmed by a PCR test positive for the SARS-CoV-2 coronavirus in smears from the nasopharynx and oropharynx.
4. Indications for hospitalization for COVID-19 treatment: a moderate condition that does not require oxygen support or low oxygen flow required through a nasal cannula or oxygen mask.
5. A urine test performed during screening, negative for pregnancy in women capable of childbearing.

Exclusion criteria

1. The need for non-invasive ventilation or high oxygen flow, or intubation of the trachea with artificial ventilation, or the use of vasopressors and/or extracorporeal membrane oxygenation at the time of assessment.
2. Decompensation of concomitant pathology, whose severity exceeds the severity of COVID-19 manifestations (for example, acute coronary syndrome, cerebral circulation disorders, acute surgical pathology requiring surgical intervention, bleeding independent of the localization, etc.).
3. Topical or systemic use of Methylene blue for any reasons at the time of evaluation or during the interval of 30 days before hospitalization.
4. Known intolerance or hypersensitivity to Methylene blue (indicated in the medical history of the patient).
5. Patients with a high probability of not surviving within the first 24 h of hospitalization, regardless of the treatment, as defined by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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24 participants in 2 patient groups, including a placebo group

Methylene blue Arm

Experimental group

Description:

The intervention is carried out in addition to the standard treatment. Administered Intervention is topical application of 0.02% Methylene blue solution in the form of repeated nasopharyngeal irrigation. The investigational drug is equipped with a spray nozzle to perform three administrations into both lower nasal passages. After three administrations on each side, it is recommended to take a deep breath so that the injected solution is distributed along the nasopharynx and oropharynx every 4 hours (5-6 times a day with a break for sleep). Duration is the period of stay of the subject, as long as there is no need for non-invasive or invasive mechanical ventilation. If the subject refuses further treatment in a hospital but does not withdraw consent to participate in the study, they should continue to take study drug after discharge from hospital, but not later than the date of the follow-up visit.

Treatment:

Drug: Methylene Blue

Saline solution Arm

Placebo Comparator group

Description:

The intervention is carried out in addition to the standard treatment. Adminestered Intervention is saline solution in the form of repeated nasopharyngeal irrigation. Dosage form, dosage, frequency and duration of intervention are the same.

Treatment:

Drug: Saline nasal spray