Low-doses Melphalan Inhalation in Patients With COVID-19 (CoronavIrus Disease 2019) Pneumonia

NCT04380376 | Unknown Phase 2

• 1 other identifier: PSRI05-20
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

COVID-19; Viral Pneumonia

Keywords

COVID; treatment; inhalation; alkylating drug; pneumonia

Outcome Measures

Primary Outcomes (3)

• 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) 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.

  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.

  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.

  Baseline vs day 7, day 14, day 28

Secondary Outcomes (5)

• CRP level

  baseline, day 7, Day 14, Day 28

• Lymphocyte count

  baseline, day 7, Day 14, Day 28

• D-dimer

  baseline, day 7, Day 14, Day 28

• IL-6

  baseline, day 7, Day 14, Day 28

• Percentage of patients without artificial lung ventilation

  baseline, day 7, Day 14, Day 28

Study Arms (2)

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

Drug: Melphalan

Standard of care group

OTHER

Patients assigned to the standard of care group will not receive any additional therapy.

Other: Standard of care

Interventions

Melphalan DRUG

Inhalations with low doses of Melphalan for 7-10 consequent days

Also known as: Alkeran

Melphalan inhalations

Standard of care OTHER

the patients will receive only SOC (standard of care) treatment

Standard of care group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Federal State Budgetary Institution, Pulmonology Scientific Research Institute: lead
• Medsi Clinic #1, Moscow: collaborator
• Moscow State University of Medicine and Dentistry: collaborator

Study Sites (2)

Kirill Zykov

Moscow, 115682, Russia

RECRUITING

Clinical hospital

Moscow, 125430, Russia

RECRUITING

Related Publications (3)

• 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.

  PMID: 11287812 BACKGROUND

• Pukhal'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.

  PMID: 19645099 BACKGROUND

• Pukhalsky 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.

  PMID: 16620792 BACKGROUND

MeSH Terms

Conditions

COVID-19; Pneumonia, Viral; Respiratory Aspiration; Pneumonia

Interventions

Melphalan; Standard of Care

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Kirill A Zykov, Prof

  Federal State Budgetary Institution, Pulmonology Scientific Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kiril A Zykov, Prof

CONTACT

+79257729462; kirillaz@inbox.ru

Evgeny Sinitsyn

CONTACT

+79269490744; sinymlad@list.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director for Science and Innovations

Model Details: Prospective, Single-center, Open-Label, Central Assessor Blinded, Comparative Study

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 8, 2020
• Study Start: April 30, 2020
• Primary Completion: October 30, 2020
• Study Completion: October 30, 2020
• Last Updated: May 12, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

RU (2)