COVID-19Phase 2MICOVNCT04380376
Low-doses Melphalan Inhalation in Patients With COVID-19 (CoronavIrus Disease 2019) Pneumonia
A Phase 2 study testing Melphalan in people with COVID-19 and Viral Pneumonia, run by Federal State Budgetary Institution, Pulmonology Scientific Research Institute at 2 sites in Russia.
Trial summary
This single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Viral Pneumonia
- What is being tested?
- Melphalan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesRussia
- Study dates
- 30 Apr 2020to 30 Oct 2020
- 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
- Age ≥18 years
- A patient must have confirmed the diagnosis of bi-lateral moderate / severe pneumonia ( viral or viral-bacterial with confirmed of suspected COVID-19).
- Presence new infiltrates or increase already available infiltrates of pulmonary infiltrates on lung CT within 48 hours before baseline.
- A patient has as minimum one of the following symptoms:
- fever >38 degrees Celsius, cough, dyspnea, SaO2 (arterial oxygen saturation) <95% (with room air)
Who cannot join
- Informed consent is withdrawn by the patient.
- The patient doesn't follow the instructions of the research staff regarding the requirements of the research protocol.
- Unable to contact the patient.
- The researcher believes that participation in the study is not in the interests of the patient and / or further participation in the study is unsafe for the patient's health.
- There is a violation of the criteria for inclusion and / or non-inclusion in the study.
- The patient has developed an adverse event, which, according to the researcher, makes further participation in the study unsafe for the patient.
- The licensing authority or ethics committee, for any reason, decides to discontinue the entire study or close this research center.
- A female patient becomes pregnant, is planning a pregnancy, or is breastfeeding while participating in this study.
Trial locations and contacts
2 sites in 1 country.
Russia2 sites, 2 recruiting
- Recruiting
Kirill Zykov
Moscow, 115682
Evgeny Sinitsyn, +79269490744, sinymlad@list.ru
Kirill Zykov, Prof, +79257729462, kirillaz@inbox.ru
- Recruiting
Clinical hospital
Moscow, 125430
Kirill Zykov, MD, +79257729462, kirillaz@inbox.ru
Evgeny Sinitsyn, +79269490744, sinymlad@list.ru
About this study
Official title: Single-center, Prospective, Open-label, Comparator Study, Blind for Central Accessor to Access the Efficacy, Safety, and Tolerability of Inhalations of Low-doses of Melphalan in Patients With Pneumonia With Confirmed or Suspected COVID-19
This single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.
Read the detailed description
It was previously shown that in ultra-low (more than 100 times lower than conventional therapeutic) doses inhalations of alkylating drug (melphalan) are effective in severe steroid-resistant bronchial asthma, a form of the disease often characterised by neutrophilic type of inflammation. The exacerbation frequency reduced after the treatment, steroid-sparing effect was shown, morphological signs of bronchial epithelial regeneration were revealed and quality of life of asthmatic patients, treated with ultra-low doses of melphalan, improved. In preclinical studies and studies with volunteers, it was found that inhalations of ultra-low doses of melphalan do not have cytotoxic properties, but have local and systemic anti-inflammatory effects and decrease the activation of lymphocytes due to blockade of heavy β-chain of the interleukin (IL)-2 surface receptor. In addition, in ultra-low concentrations, alkylating agents are able to disrupt the cell signalling through the receptor for tumor necrosis factor (TNF), thereby exerting a protective effect from the cytotoxic activity of TNF-α, which leads to the anti-inflammatory response.
Taking into account, that severe cases of COVID are characterised with hyperergic inflammatory response (and in some cases even with the development of "cytokine storm") it can be assumed that the inhalation use of low-doses of melphalan due to its anti-inflammatory properties can be effective treatment for patients with COVID-associated pneumonia.
- Conditions
- COVID-19, Viral Pneumonia
- Being tested
- Melphalan, Standard of care
- Keywords
- COVID, treatment, inhalation, alkylating drug, pneumonia
- Medical subject headings
- COVID-19, Pneumonia, Viral, Respiratory Aspiration, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelphalanDrug
Also called Alkeran
Inhalations with low doses of Melphalan for 7-10 consequent days
Standard of careOther
the patients will receive only SOC (standard of care) treatment
| Study group | Role | What they receive |
|---|---|---|
| Melphalan inhalations | Experimental | Inhalations with Melphalan 0,1 mg dissolved in 2 ml sodium chloride (NaCl) 0,9% 1 per day for 7-10 consequent days Receives: Drug: Melphalan |
| Standard of care group | Other | Patients assigned to the standard of care group will not receive any additional therapy. Receives: Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
The changes of COVID Ordinal Outcomes Scale
The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier)
- Death
- Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT
- Hospitalized with intubation and mechanical ventilation
- Hospitalized on non-invasive ventilation or high flow oxygen.
- Hospitalized on a mask or nasal prongs.
- Hospitalized no oxygen therapy.
- Ambulatory, with limitation of activities.
- Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.
Measured: baseline vs Day 14, day 28
Percentage of the patients with Clinical Recovery
Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first.
Normalization and improvement criteria:
- Fever - <37°C,
- Respiratory rate - ≤24/minute on room air,
- Oxygen saturation - >94% on room air,
- Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
Measured: baseline vs day 7, day 14, day 28
The changes of the Borg's scale
The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.
Measured: Baseline vs day 7, day 14, day 28
Secondary outcomes (5)
CRP level
Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.
Measured: baseline, day 7, Day 14, Day 28
Lymphocyte count
Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.
Measured: baseline, day 7, Day 14, Day 28
D-dimer
Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.
Measured: baseline, day 7, Day 14, Day 28
IL-6
Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.
Measured: baseline, day 7, Day 14, Day 28
Percentage of patients without artificial lung ventilation
Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.
Measured: baseline, day 7, Day 14, Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2020
- Study start30 Apr 2020
- Primary completion30 Oct 2020 (estimated)
- Study completion30 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, Single-center, Open-Label, Central Assessor Blinded, Comparative Study
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal State Budgetary Institution, Pulmonology Scientific Research Institute
- Sponsor type
- Other government
- Collaborators
- Medsi Clinic #1, Moscow, Moscow State University of Medicine and Dentistry
- Responsible party
- Principal investigator, Kirill Zykov, Federal State Budgetary Institution, Pulmonology Scientific Research Institute
- Investigators
- Kirill A Zykov, Prof, Principal investigator, Federal State Budgetary Institution, Pulmonology Scientific Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04380376
- Sponsor's protocol ID
- PSRI05-20
- Acronym
- MICOV
- Status last verified
- May 2020
- First submitted
- 6 May 2020
- Last updated
- 12 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pukhalsky AL, Shmarina GV. Stimulatory and protective effects of alkylating agents applied in ultra-low concentrations. Pharmacology. 2001;62(3):129-32. doi: 10.1159/000056084.
PubMed 11287812Pukhal'skii AL, Shmarina GV, Zykov KA, Aleshkin VA. [Effect of steroid therapy on the clinical course of bronchial asthma]. Vestn Ross Akad Med Nauk. 2009;(6):3-9. Russian.
PubMed 19645099Pukhalsky A, Shmarina G, Alioshkin V, Sabelnikov A. Alkylating drugs applied in non-cytotoxic doses as a novel compounds targeting inflammatory signal pathway. Biochem Pharmacol. 2006 Nov 30;72(11):1432-8. doi: 10.1016/j.bcp.2006.03.008. Epub 2006 Mar 14.
PubMed 16620792
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-center, Prospective, Open-label, Comparator Study, Blind for Central Accessor to Access the Efficacy, Safety, and Tolerability of Inhalations of Low-doses of Melphalan in Patients With Pneumonia With Confirmed or Suspected COVID-19
- ClinicalTrials.gov ID
- NCT04380376
- Acronym / sponsor ID
- MICOV / PSRI05-20
- Conditions
- COVID-19, Viral Pneumonia
- Keywords
- COVID, treatment, inhalation, alkylating drug, pneumonia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Federal State Budgetary Institution, Pulmonology Scientific Research InstituteOther government
- Collaborators
- Medsi Clinic #1, Moscow, Moscow State University of Medicine and Dentistry
- Study start
- 30 Apr 2020 (actual)
- Primary completion
- 30 Oct 2020 (estimated)
- Study completion
- 30 Oct 2020 (estimated)
- First posted
- 8 May 2020 (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 single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.
Detailed description
It was previously shown that in ultra-low (more than 100 times lower than conventional therapeutic) doses inhalations of alkylating drug (melphalan) are effective in severe steroid-resistant bronchial asthma, a form of the disease often characterised by neutrophilic type of inflammation. The exacerbation frequency reduced after the treatment, steroid-sparing effect was shown, morphological signs of bronchial epithelial regeneration were revealed and quality of life of asthmatic patients, treated with ultra-low doses of melphalan, improved. In preclinical studies and studies with volunteers, it was found that inhalations of ultra-low doses of melphalan do not have cytotoxic properties, but have local and systemic anti-inflammatory effects and decrease the activation of lymphocytes due to blockade of heavy β-chain of the interleukin (IL)-2 surface receptor. In addition, in ultra-low concentrations, alkylating agents are able to disrupt the cell signalling through the receptor for tumor necrosis factor (TNF), thereby exerting a protective effect from the cytotoxic activity of TNF-α, which leads to the anti-inflammatory response.
Taking into account, that severe cases of COVID are characterised with hyperergic inflammatory response (and in some cases even with the development of "cytokine storm") it can be assumed that the inhalation use of low-doses of melphalan due to its anti-inflammatory properties can be effective treatment for patients with COVID-associated pneumonia.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, Single-center, Open-Label, Central Assessor Blinded, Comparative Study
| Arm | Type | Receives |
|---|---|---|
| Melphalan inhalations | Experimental | Drug: MelphalanInhalations with Melphalan 0,1 mg dissolved in 2 ml sodium chloride (NaCl) 0,9% 1 per day for 7-10 consequent days |
| Standard of care group | Other | Other: Standard of carePatients assigned to the standard of care group will not receive any additional therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥18 years
- A patient must have confirmed the diagnosis of bi-lateral moderate / severe pneumonia ( viral or viral-bacterial with confirmed of suspected COVID-19).
- Presence new infiltrates or increase already available infiltrates of pulmonary infiltrates on lung CT within 48 hours before baseline.
- A patient has as minimum one of the following symptoms:
- fever >38 degrees Celsius, cough, dyspnea, SaO2 (arterial oxygen saturation) <95% (with room air)
Key exclusion criteria (8 listed)
- Informed consent is withdrawn by the patient.
- The patient doesn't follow the instructions of the research staff regarding the requirements of the research protocol.
- Unable to contact the patient.
- The researcher believes that participation in the study is not in the interests of the patient and / or further participation in the study is unsafe for the patient's health.
- There is a violation of the criteria for inclusion and / or non-inclusion in the study.
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 |
|---|---|---|
| MelphalanAlso: AlkeranInhalations with low doses of Melphalan for 7-10 consequent days | Drug | Melphalan inhalations |
| Standard of carethe patients will receive only SOC (standard of care) treatment | Other | Standard of care group |
Primary outcome
The changes of COVID Ordinal Outcomes Scale
Time frame: baseline vs Day 14, day 28
The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) 1. Death 2. Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT 3. Hospitalized with intubation and mechanical ventilation 4. Hospitalized on non-invasive ventilation or high flow oxygen. 5. Hospitalized on a mask or nasal prongs. 6. Hospitalized no oxygen therapy. 7. Ambulatory, with limitation of activities. 8. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.
Percentage of the patients with Clinical Recovery
Time frame: baseline vs day 7, day 14, day 28
Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: * Fever - <37°C, * Respiratory rate - ≤24/minute on room air, * Oxygen saturation - >94% on room air, * Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
The changes of the Borg's scale
Time frame: Baseline vs day 7, day 14, day 28
The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.
5 secondary outcomes
CRP level
Time frame: baseline, day 7, Day 14, Day 28
Lymphocyte count
Time frame: baseline, day 7, Day 14, Day 28
D-dimer
Time frame: baseline, day 7, Day 14, Day 28
IL-6
Time frame: baseline, day 7, Day 14, Day 28
Percentage of patients without artificial lung ventilation
Time frame: baseline, day 7, Day 14, Day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
- Background: PubMed 11287812Pukhalsky AL, Shmarina GV. Stimulatory and protective effects of alkylating agents applied in ultra-low concentrations. Pharmacology. 2001;62(3):129-32. doi: 10.1159/000056084.
- Background: PubMed 19645099Pukhal'skii AL, Shmarina GV, Zykov KA, Aleshkin VA. [Effect of steroid therapy on the clinical course of bronchial asthma]. Vestn Ross Akad Med Nauk. 2009;(6):3-9. Russian.
- Background: PubMed 16620792Pukhalsky A, Shmarina G, Alioshkin V, Sabelnikov A. Alkylating drugs applied in non-cytotoxic doses as a novel compounds targeting inflammatory signal pathway. Biochem Pharmacol. 2006 Nov 30;72(11):1432-8. doi: 10.1016/j.bcp.2006.03.008. Epub 2006 Mar 14.
- Individual participant dataSharing planned: No
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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.
Kirill A Zykov, Prof principal investigator
Federal State Budgetary Institution, Pulmonology Scientific Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melphalan in people with COVID-19 and Viral Pneumonia, run by Federal State Budgetary Institution, Pulmonology Scientific Research Institute at 2 sites 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 8 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: status not confirmed, as of the sponsor's last update on 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kiril A Zykov, Prof (+79257729462, kirillaz@inbox.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The changes of COVID Ordinal Outcomes Scale (time frame: baseline vs Day 14, day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04380376, which also lists 3 linked publications.
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 12 May 2020; AzTrials last refreshed its copy on 7 Nov 2026.