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Efficacy and Safety of MTX-loaded Nanoparticles to Treat Severe COVID-19 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04352465
Recruitment Status : Not yet recruiting
First Posted : April 20, 2020
Last Update Posted : April 29, 2020
Sponsor:
Collaborators:
InCor Heart Institute
Hospital Santa Marcelina
PREVENT SENIOR PRIVATE OPERADORA DE SAÚDE LTDA
Information provided by (Responsible Party):
Azidus Brasil

Brief Summary:
The aim of this study is to evaluate the efficacy and safety of MTX-loaded nanoparticles in three different doses to treat severe COVID-19 patients.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Methotrexate Phase 1 Phase 2

Detailed Description:

Patients with acute lung injury caused by COVID-19 disease are experiencing an inflammatory reaction that can be harmful and worsen the severity of the clinical condition. Thus, the use of MTX-loaded nanoparticules in patients with acute lung injury secondary to COVID-19 aims to decrease the exacerbated inflammatory reaction leading to a decrease in cell damage caused by this inflammatory process in patients.

The study will be divided in 3 phases:

Phase A (n=4): IV administration of 20 mg of MTX-loaded nanoparticles. Four doses of Investigational Product (IP) will be administered, once per week. If patients show clinical improvement after 2nd or 3rd administration, the next phase will start.

Phase B (n=12): IV administration of 30 mg of MTX-loaded nanoparticles. Four doses of Investigational Product (IP) will be administered, once per week. If patients show clinical improvement after 2nd or 3rd administration, the next phase will start.

Fase C (n=26): IV administration of 40 mg of MTX-loaded nanoparticules. Four doses of Investigational Product (IP) will be administered, once per week.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

The study will be divided in 3 phases:

Phase A: subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses).

Phase B: will only start after 2nd or 3rd administration of phase A. Subjects will be dosed 30 mg of MTX IV, once per week (total of 4 doses).

Phase C: will only start after 2nd or 3rd administration of phase B. Subjects will be dosed 40 mg of MTX IV, once per week (total of 4 doses).

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Acute Respiratory Syndrome Resulting From the Inflammatory Process of COVID-19 Infection Using Methotrexate-loaded Nanoparticles: A Phase I/II Study
Estimated Study Start Date : May 1, 2020
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A
Phase A: subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses).
Drug: Methotrexate
Phase A: Subjects will be dosed 20 mg of MTX IV, once per week (total of 4 doses).
Other Name: MTX-loaded nanoparticles

Experimental: B
Phase B: will only start after 2nd or 3rd administration of phase A. Subjects will be dosed 30 mg of MTX IV, once per week (total of 4 doses).
Drug: Methotrexate
Phase B: Subjects will be dosed 30 mg of MTX IV, once per week (total of 4 doses).
Other Name: MTX-loaded nanoparticles

Experimental: C
Phase C: will only start after 2nd or 3rd administration of phase B. Subjects will be dosed 40 mg of MTX IV, once per week (total of 4 doses).
Drug: Methotrexate
Phase C: Subjects will be dosed 40 mg of MTX IV, once per week (total of 4 doses).
Other Name: MTX-loaded nanoparticles




Primary Outcome Measures :
  1. Change in clinical conditions [ Time Frame: 21 days ]
    Clinical condition will be measured by lung injuries


Secondary Outcome Measures :
  1. Change of Clinical symptoms - respiratory rate [ Time Frame: 21 days ]
    Evaluation of Pneumonia change

  2. Hypoxia [ Time Frame: 21 days ]
    oxygen saturation

  3. Changes of blood oxygen [ Time Frame: 21 days ]
    PaO2 / FiO2 ratio

  4. Inflammatory parameters [ Time Frame: 21 days ]
    C-reactive protein and ferritin

  5. Evolution of Acute Respiratory Syndrome [ Time Frame: 21 days ]
    Time to wean off oxygen invasive ventilatory support

  6. Hospital discharge [ Time Frame: 21 dyas ]
    Time to be discharged from hospital

  7. ICU discharge [ Time Frame: 21 days ]
    Time to be discharged from ICU

  8. Rate of mortality [ Time Frame: 4 months ]
    Evaluation of change in acute respiratory syndrome



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent from patient or legal representative.
  2. Male or female, aged ≥ 18 years;
  3. Acute respiratory distress syndrome; with imminent risk of death, and with chest CT scan with pulmonary impairment greater than 50%;
  4. Confirmed or pending diagnosis of COVID-19.

Exclusion Criteria:

  1. Pleural effusion > 150mL or ascites > 200mL;
  2. Chronic liver disease;
  3. ALT and AST serum levels >= three times the upper limit of normality;
  4. Renal failure (dialysis)
  5. Multiple organ failure

7. Concomitant use or use in the last 7 days of cell therapy with stem cells; 8. Any clinical or laboratory condition or comorbidity that, at medical discretion, 9. Known hypersensitivity to the investigational product; 10. Subject who is pregnant or lactating


Information from the National Library of Medicine

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): NCT04352465


Contacts
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Contact: Rodrido Esper, MD, PhD +55 11 98179-7949 dr.rodrigo.esper@preventsenior.com.br
Contact: Luciana Ferrara +55 19 981428814 luciana.ferrara@azidusbrasil.com.br

Locations
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Brazil
Prevent Senior Private Operadora de Saúde LTDA.
São Paulo, Brazil
Contact: Rodrigo Barbosa Esper         
Sponsors and Collaborators
Azidus Brasil
InCor Heart Institute
Hospital Santa Marcelina
PREVENT SENIOR PRIVATE OPERADORA DE SAÚDE LTDA
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Responsible Party: Azidus Brasil
ClinicalTrials.gov Identifier: NCT04352465    
Other Study ID Numbers: LDE-MTX_COVID19
First Posted: April 20, 2020    Key Record Dates
Last Update Posted: April 29, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors