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

NCT ID: NCT04380376

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-30
• Study Completion Date: 2020-10-30

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

Melphalan

Intervention Type: DRUG

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

Standard of care group

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

Group Type: OTHER

Standard of care

Intervention Type: OTHER

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

Interventions

Melphalan

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

Intervention Type: DRUG

Standard of care

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

Intervention Type: OTHER

Other Intervention Names

Alkeran

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years

2. A patient must have confirmed the diagnosis of bi-lateral moderate / severe pneumonia ( viral or viral-bacterial with confirmed of suspected COVID-19).

3. Presence new infiltrates or increase already available infiltrates of pulmonary infiltrates on lung CT within 48 hours before baseline.

4. A patient has as minimum one of the following symptoms:

fever >38 degrees Celsius, cough, dyspnea, SaO2 (arterial oxygen saturation) <95% (with room air)

Exclusion Criteria

1. Informed consent is withdrawn by the patient.

2. The patient doesn't follow the instructions of the research staff regarding the requirements of the research protocol.

3. Unable to contact the patient.

4. 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.

5. There is a violation of the criteria for inclusion and / or non-inclusion in the study.

6. The patient has developed an adverse event, which, according to the researcher, makes further participation in the study unsafe for the patient.

7. The licensing authority or ethics committee, for any reason, decides to discontinue the entire study or close this research center.

8. A female patient becomes pregnant, is planning a pregnancy, or is breastfeeding while participating in this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medsi Clinic #1, Moscow

OTHER

Sponsor Role: collaborator

Moscow State University of Medicine and Dentistry

OTHER

Sponsor Role: collaborator

Federal State Budgetary Institution, Pulmonology Scientific Research Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Kirill Zykov

Deputy director for Science and Innovations

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kirill A Zykov, Prof

Role: PRINCIPAL_INVESTIGATOR

Federal State Budgetary Institution, Pulmonology Scientific Research Institute

Locations

Kirill Zykov

Moscow, , Russia

Site Status: RECRUITING

Clinical hospital

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Kiril A Zykov, Prof

Role: CONTACT

kirillaz@inbox.ru

+79257729462

Evgeny Sinitsyn

Role: CONTACT

sinymlad@list.ru

+79269490744

Facility Contacts

Evgeny Sinitsyn

Role: primary

sinymlad@list.ru

+79269490744

Kirill Zykov, Prof

Role: backup

kirillaz@inbox.ru

+79257729462

Kirill Zykov, MD

Role: primary

kirillaz@inbox.ru

+79257729462

Evgeny Sinitsyn

Role: backup

sinymlad@list.ru

+79269490744

References

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.

Reference Type: BACKGROUND

PMID: 11287812 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19645099 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16620792 (View on PubMed)

Other Identifiers

PSRI05-20

Identifier Type: -

Identifier Source: org_study_id