Covid19Phase 2COMBATNCT05004805
COVID-19 Methylene Blue Antiviral Treatment
A Phase 2 study testing Methylene Blue and Saline nasal spray in people with Covid19, run by Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences at 1 site in Russia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Methylene Blue and Saline nasal spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteRussia
- Study dates
- 6 Aug 2021to 12 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18 and over at the time of signing the informed consent.
- The patient is willing and able to give written informed consent to participate in the study and follow the procedures specified in the protocol.
- Diagnosed with COVID-19, confirmed by a PCR test positive for the SARS-CoV-2 coronavirus in smears from the nasopharynx and oropharynx.
- 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.
- A urine test performed during screening, negative for pregnancy in women capable of childbearing.
Who cannot join
- 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.
- 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.).
- Topical or systemic use of Methylene blue for any reasons at the time of evaluation or during the interval of 30 days before hospitalization.
- Known intolerance or hypersensitivity to Methylene blue (indicated in the medical history of the patient).
- 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 locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Conditions
- Covid19
- Being tested
- Methylene Blue, Saline nasal spray
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene BlueDrug
Also called MB Spray
MB administered topically as a 0.02% solution nasal spray in COVID-19 patients requiring hospitalization.
Saline nasal sprayDrug
Also called Placebo Spray
Saline administered topically as nasal spray in COVID-19 patients requiring hospitalization.
| Study group | Role | What they receive |
|---|---|---|
| Methylene blue Arm | Experimental | 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. Receives: Drug: Methylene Blue |
| Saline solution Arm | Placebo comparator | 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. Receives: Drug: Saline nasal spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recovery
A negative PCR test result for the SARS-CoV-2 using nasopharyngeal and oropharyngeal swabs
Measured: Day 14 after randomization
Recovery
A negative PCR test result for the SARS-CoV-2 using nasopharyngeal and oropharyngeal swabs
Measured: Day 28 after randomization
Secondary outcomes (5)
Clinical responce
Determined by the investigator
Measured: Day 28 after randomization
Overall therapeutic response
The overall therapeutic response defined as a "general cure" or "treatment failure" and is calculated for each patient according to the patient's combination of clinical, radiological response, and PCR result.
Measured: Day 28 after randomization
Resolution rate
The rate of resolution of fever, normalization of SpO2 (NEWS2), dynamics of target laboratory parameters (C-reactive protein, D-dimer)
Measured: Day 28 after randomization
Clinical responce FUV
Determined by the investigator
Measured: Follow up visit, week 4 ± 3 days after discharge from the hospital
Overall therapeutic response FUV
The overall therapeutic response defined as a "general cure" or "treatment failure" and is calculated for each patient according to the patient's combination of clinical, radiological response, and PCR result.
Measured: Follow up visit, week 4 ± 3 days after discharge from the hospital
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2021
- Study start6 Aug 2021
- Primary completion12 Dec 2021
- Study completion12 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-center, blind, randomized, controlled clinical trial.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences
- Sponsor type
- Other government
- Collaborators
- Irkutsk State Medical University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05004805
- Sponsor's protocol ID
- COMBAT
- Acronym
- COMBAT
- Status last verified
- Feb 2022
- First submitted
- 11 Aug 2021
- Last updated
- 9 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COVID-19 Methylene Blue Antiviral Treatment
- ClinicalTrials.gov ID
- NCT05004805
- Acronym / sponsor ID
- COMBAT / COMBAT
- Conditions
- Covid19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of SciencesOther government
- Collaborators
- Irkutsk State Medical University
- Study start
- 6 Aug 2021 (actual)
- Primary completion
- 12 Dec 2021 (actual)
- Study completion
- 12 Dec 2021 (actual)
- First posted
- 13 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Single-center, blind, randomized, controlled clinical trial.
| Arm | Type | Receives |
|---|---|---|
| Methylene blue Arm | Experimental | Drug: Methylene BlueThe 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. |
| Saline solution Arm | Placebo comparator | Drug: Saline nasal sprayThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women aged 18 and over at the time of signing the informed consent.
- The patient is willing and able to give written informed consent to participate in the study and follow the procedures specified in the protocol.
- Diagnosed with COVID-19, confirmed by a PCR test positive for the SARS-CoV-2 coronavirus in smears from the nasopharynx and oropharynx.
- 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.
- A urine test performed during screening, negative for pregnancy in women capable of childbearing.
Key exclusion criteria (5 listed)
- 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.
- 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.).
- Topical or systemic use of Methylene blue for any reasons at the time of evaluation or during the interval of 30 days before hospitalization.
- Known intolerance or hypersensitivity to Methylene blue (indicated in the medical history of the patient).
- Patients with a high probability of not surviving within the first 24 h of hospitalization, regardless of the treatment, as defined by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylene BlueAlso: MB SprayMB administered topically as a 0.02% solution nasal spray in COVID-19 patients requiring hospitalization. | Drug | Methylene blue Arm |
| Saline nasal sprayAlso: Placebo SpraySaline administered topically as nasal spray in COVID-19 patients requiring hospitalization. | Drug | Saline solution Arm |
Primary outcome
Recovery
Time frame: Day 14 after randomization
A negative PCR test result for the SARS-CoV-2 using nasopharyngeal and oropharyngeal swabs
Recovery
Time frame: Day 28 after randomization
A negative PCR test result for the SARS-CoV-2 using nasopharyngeal and oropharyngeal swabs
5 secondary outcomes
Clinical responce
Time frame: Day 28 after randomization
Overall therapeutic response
Time frame: Day 28 after randomization
Resolution rate
Time frame: Day 28 after randomization
Clinical responce FUV
Time frame: Follow up visit, week 4 ± 3 days after discharge from the hospital
Overall therapeutic response FUV
Time frame: Follow up visit, week 4 ± 3 days after discharge from the hospital
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylene Blue and Saline nasal spray in people with Covid19, run by Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recovery (time frame: Day 14 after randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2022.