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

University of Sao Paulo General Hospital100 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Interventions

Methotrexate-LDE phase 1DRUG

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

Methotrexate-LDE phase 2DRUG

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

Placebo-LDE phase 2DRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Locations (3)

Heart Institute (InCor) - University of São Paulo Medical School, São Paulo, Brazil

São Paulo, São Paulo, Brazil

RECRUITING

Hospital Santa Marcelina

São Paulo, São Paulo, Brazil

NOT_YET_RECRUITING

Institute Prevent Senior

São Paulo, São Paulo, Brazil

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

Duration of hospital stay

Compare the duration of hospital stay between groups

Time frame: 30 days after randomization

Secondary Outcomes

Number of participants requiring mechanical ventilation

The secondary outcome is the need for mechanical ventilation between groups

Time frame: 15 days after randomization

Number of participants requiring vasoactive drugs

The secondary outcome is the need for vasoactive drugs between groups

Time frame: 15 days after randomization

Number of participants requiring renal replacement therapy

The secondary outcome is the need for renal replacement therapy between groups

Time frame: 15 days after randomization

Incidence of secondary infection

The secondary outcome is the incidence of secondary infection between groups

Time frame: 15 days after randomization

Sequential Organ Failure Assessment (SOFA) score

The secondary outcome is the comparison of Sequential Organ Failure Assessment (SOFA) score between groups