Treatment of Patients With Mild Coronavirus-19 (COVID-19) Disease With Methotrexate Associated to LDL Like Nanoparticles (Nano-COVID19) (Nano-COVID19)

January 13, 2021 updated by: Raul Cavalcante Maranhão, University of Sao Paulo General Hospital

Two Phases Clinical Trial to Evaluate Safety and Efficacy of Methotrexate Associated to LDL Like Nanoparticles (LDE-MTX) in the Treatment of Patients With Mild Coronavirus-19 (COVID-19) Disease.

The investigators propose a prospective, randomized, double-blind, placebo-controlled study, conducted in two phases. The purpose of the study is to evaluate the safety and efficacy of methotrexate in a cholesterol-rich non-protein nanoparticle (MTX -LDE) in adults diagnosed with mild Coronavirus-19(COVID-19) disease.

A total of 100 patients will be randomized to receive MTX-LDE or placebo each 7 days, up to 3 times, during in hospital treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The objective of the study is to evaluate the safety and efficacy of (MTX -LDE) in patients with mild Coronavirus-19 (COVID-19) disease.

In phase 1, firstly 3 patients with moderate COVID-19 disease will receive MTX-LDE IV 15mg each 7 days, up to 3 times, during hospitalization. After that, 9 patients with moderate COVID-19 disease will receive MTX-LDE IV 30mg each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of adverse events.The purpose of this phase will be evaluate safety and pharmacokinetics.

If no objection by data and safety monitoring board (DSMB), will be authorized to start the second phase.

In phase 2, 88 patients with moderate COVID-19 disease will be randomized to receive MTX-LDE IV 30mg or placebo-LDE IV each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of any trial endpoints or other adverse events.The primary endpoint of this phase will be reduction in duration of hospitalization stay between groups.

Patients will undergo clinical and laboratory safety evaluations daily. An algorithm for drug suspension based on clinical and laboratory finding will be followed.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • SP
      • São Paulo, SP, Brazil, 05403900
        • Recruiting
        • Heart Institute (InCor) - University of São Paulo Medical School, São Paulo, Brazil
        • Contact:
      • São Paulo, SP, Brazil
        • Not yet recruiting
        • Hospital Santa Marcelina
        • Contact:
          • Jose Salvador Oliveira, MD;PhD
      • São Paulo, SP, Brazil
        • Not yet recruiting
        • Institute Prevent Senior
        • Contact:
          • Rodrigo Esper, MD;PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients who were hospitalized with confirmed COVID-19
  • Mild Coronavirus-19 disease (WHO Coronavirus-19 scale < 5)
  • Fewer than 14 days since symptom onset.
  • Female patient is not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile.
  • Female patient is of childbearing potential must has a negative pregnancy test.
  • Signing the study informed consent.

Exclusion Criteria:

  • Need for oxygen supplementation >4 L/min via nasal cannula or ≥40% via Venturi mask.
  • Need for oxygen supplementation via high-flow nasal cannula.
  • Need for invasive mechanical ventilation.
  • Extent of pulmonary involvement > 50% by CT scan.
  • Chronic renal failure (estimated glomerular filtration rate <30 mL/min/1.73 m2)
  • History of liver cirrhosis (Bilirubins levels > 3mg/dl)
  • History of heart failure ( Ejection fraction <40%)
  • History of Steven-Johnson disease
  • History of stroke in the last 6 months
  • History of sickle cell disease
  • Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers.
  • Prior history of chronic hepatitis B or C infection and known HIV positive.
  • Patient undergoing chemotherapy for cancer
  • Sepsis caused by fungal or multidrug resistant gram-negative bacteria
  • Known allergy to methotrexate.
  • Body mass index(BMI) > 40 or <18.5
  • Pregnancy or breastfeeding.
  • Patients enrolled in other clinical trials in the last 12 months
  • Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MTX-LDE phase 1
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
Drug: Methotrexate-LDE phase 1

3 patients will receive MTX-LDE at the dose of 15mg IV each 7 days during hospitalization, up to 3 times . After that, 9 patients will receive MTX-LDE at the dose of 30mg IV each 7 days during hospitalization, up to 3 times .

All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of MTX-LDE

Other Names:
  • MTX-LDE phase 1
Experimental: MTX-LDE phase 2
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
Drug: Methotrexate-LDE phase 2
44 patients will receive MTX-LDE at the dose of 30mg IV each 7 days during hospitalization, up to 3 times dose of 30mg IV each 7 days during hospitalization, up to 3 times . All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of MTX-LDE
Other Names:
  • MTX-LDE phase 2
Placebo Comparator: Placebo-LDE phase 2
Lipid nanoparticle (LDE)
Drug: Placebo-LDE phase 2
44 patients will receive Placebo-LDE IV each 7 days during hospitalization, up to 3 times dose of 30mg IV each 7 days during hospitalization, up to 3 times . All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of Placebo-LDE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of hospital stay
Time Frame: 30 days after randomization
Compare the duration of hospital stay between groups
30 days after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants requiring mechanical ventilation
Time Frame: 15 days after randomization
The secondary outcome is the need for mechanical ventilation between groups
15 days after randomization
Number of participants requiring vasoactive drugs
Time Frame: 15 days after randomization
The secondary outcome is the need for vasoactive drugs between groups
15 days after randomization
Number of participants requiring renal replacement therapy
Time Frame: 15 days after randomization
The secondary outcome is the need for renal replacement therapy between groups
15 days after randomization
Incidence of secondary infection
Time Frame: 15 days after randomization
The secondary outcome is the incidence of secondary infection between groups
15 days after randomization
Sequential Organ Failure Assessment (SOFA) score
Time Frame: Baseline and change from baseline to 15 days after randomization
The secondary outcome is the comparison of Sequential Organ Failure Assessment (SOFA) score between groups
Baseline and change from baseline to 15 days after randomization
World Health Organization (WHO) COVID-19 score
Time Frame: Baseline and change from baseline to 15 days after randomization
The secondary outcome is the comparison of World Health Organization (WHO) COVID-19 clinical score between groups
Baseline and change from baseline to 15 days after randomization
Interleukin 6 (IL-6)
Time Frame: Baseline and change from baseline to 15 days after randomization
The secondary outcome is the comparison of IL-6 levels between groups
Baseline and change from baseline to 15 days after randomization
Dimer-D
Time Frame: Baseline and change from baseline to 15 days after randomization
The secondary outcome is the comparison of dimer-D levels between groups
Baseline and change from baseline to 15 days after randomization
Chest CT scan
Time Frame: Baseline and change from baseline to 15 days after randomization
The secondary outcome is the comparison of chest CT scan between groups
Baseline and change from baseline to 15 days after randomization
Incidence and severity of laboratory alterations
Time Frame: 30 days after randomization
The secondary outcome is the comparison of red blood cells; white blood cells;Platelets; Urea;Creatinine levels between groups
30 days after randomization
Clinical side effects
Time Frame: 30 days after randomization
Compare the incidence of clinical significant symptoms (new and persistent stomatitis, vomiting, diarrhea, alopecia, neurotoxicity, bradycardia, hypotension, local pain) reported between groups.
30 days after randomization
Other adverse events
Time Frame: 30 days after randomization
Compare the incidence of other adverse events (not expected) between groups
30 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Collaborators

Hospital Santa Marcelina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 27, 2020

Primary Completion (Anticipated)

March 15, 2021

Study Completion (Anticipated)

July 15, 2021

Study Registration Dates

First Submitted

October 24, 2020

First Submitted That Met QC Criteria

October 29, 2020

First Posted (Actual)

October 30, 2020

Study Record Updates

Last Update Posted (Actual)

January 14, 2021

Last Update Submitted That Met QC Criteria

January 13, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 36746020.5.1001.0068

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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