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.
Overview
- Phase
- Phase 1
- Intervention
- Methotrexate-LDE phase 1
- Conditions
- Coronavirus
- Sponsor
- University of Sao Paulo General Hospital
- Enrollment
- 100
- Locations
- 3
- Primary Endpoint
- Duration of hospital stay
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
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.
Investigators
Raul Cavalcante Maranhão
MD; PHD. Director Lipid Metabolism Laboratory, Heart Institute
University of Sao Paulo General Hospital
Eligibility Criteria
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
Arms & Interventions
MTX-LDE phase 1
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
Intervention: Methotrexate-LDE phase 1
MTX-LDE phase 2
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
Intervention: Methotrexate-LDE phase 2
Placebo-LDE phase 2
Lipid nanoparticle (LDE)
Intervention: Placebo-LDE phase 2
Outcomes
Primary Outcomes
Duration of hospital stay
Time Frame: 30 days after randomization
Compare the duration of hospital stay between groups
Secondary Outcomes
- Other adverse events(30 days after randomization)
- Sequential Organ Failure Assessment (SOFA) score(Baseline and change from baseline to 15 days after randomization)
- Number of participants requiring mechanical ventilation(15 days after randomization)
- Chest CT scan(Baseline and change from baseline to 15 days after randomization)
- Interleukin 6 (IL-6)(Baseline and change from baseline to 15 days after randomization)
- Number of participants requiring renal replacement therapy(15 days after randomization)
- World Health Organization (WHO) COVID-19 score(Baseline and change from baseline to 15 days after randomization)
- Dimer-D(Baseline and change from baseline to 15 days after randomization)
- Clinical side effects(30 days after randomization)
- Incidence of secondary infection(15 days after randomization)
- Number of participants requiring vasoactive drugs(15 days after randomization)
- Incidence and severity of laboratory alterations(30 days after randomization)