Low-doses Melphalan Inhalation in Patients With COVID-19 (CoronavIrus Disease 2019) Pneumonia (MICOV)
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|ClinicalTrials.gov Identifier: NCT04380376|
Recruitment Status : Recruiting
First Posted : May 8, 2020
Last Update Posted : May 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19 Viral Pneumonia||Drug: Melphalan Other: Standard of care||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Prospective, Single-center, Open-Label, Central Assessor Blinded, Comparative Study|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||An independent central blinded assessor will be blinded to study treatment and will review the clinical response assessments. In case of a discrepancy with the Investigator's assignment of clinical response, the adjudication committee's assessment will prevail.|
|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|
|Actual Study Start Date :||April 30, 2020|
|Estimated Primary Completion Date :||October 30, 2020|
|Estimated Study Completion Date :||October 30, 2020|
Experimental: Melphalan inhalations
Inhalations with Melphalan 0,1 mg dissolved in 2 ml sodium chloride (NaCl) 0,9% 1 per day for 7-10 consequent days
Inhalations with low doses of Melphalan for 7-10 consequent days
Other Name: Alkeran
Standard of care group
Patients assigned to the standard of care group will not receive any additional therapy.
Other: Standard of care
the patients will receive only SOC (standard of care) treatment
- 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)
- 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.
- 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.
- CRP level [ Time Frame: baseline, day 7, Day 14, Day 28 ]Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.
- Lymphocyte count [ Time Frame: baseline, day 7, Day 14, Day 28 ]Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.
- D-dimer [ Time Frame: baseline, day 7, Day 14, Day 28 ]Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.
- IL-6 [ Time Frame: baseline, day 7, Day 14, Day 28 ]Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.
- Percentage of patients without artificial lung ventilation [ Time Frame: baseline, day 7, Day 14, Day 28 ]Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04380376
|Contact: Kiril A Zykov, Proffirstname.lastname@example.org|
|Contact: Evgeny Sinitsynemail@example.com|
|Moscow, Russian Federation, 115682|
|Contact: Evgeny Sinitsyn +79269490744 firstname.lastname@example.org|
|Contact: Kirill Zykov, Prof +79257729462 email@example.com|
|Sub-Investigator: Evgeny Sinitsyn, MD|
|Sub-Investigator: Anna Rvacheva, PhD|
|Moscow, Russian Federation, 125430|
|Contact: Kirill Zykov, MD +79257729462 firstname.lastname@example.org|
|Contact: Evgeny Sinitsyn +79269490744 email@example.com|
|Principal Investigator:||Kirill A Zykov, Prof||Federal State Budgetary Institution, Pulmonology Scientific Research Institute|