Treatment of Patients With Atherosclerotic Disease With Methotrexate-associated to LDL Like Nanoparticles

• Status: Recruiting
• Trial end date: 2023-10-12
• Target enrollment: 0
• Participant gender: All

Summary

The investigators propose a prospective, randomized, double-blind, placebo-controlled study. The purpose of the study is to evaluate the safety and efficacy of an anti-inflammatory agent methotrexate in a cholesterol-rich non-protein nanoparticle (MTX-LDE) in patients with stable coronary disease.

Patients with multi-vessels stable coronary disease will be randomized to receive MTX-LDE IV or placebo-LDE IV each 7 days for 12 weeks. The primary and main secondary endpoints will be analyzed by coronary and aortic CT angiography, that will be performed before the first treatment cycle, four weeks after the last drug infusion and 12 months after randomization. Patients will undergo clinical and laboratory safety evaluations before each treatment cycle, four weeks after the last cycle and 12 months after randomization.

An algorithm for drug suspension based on clinical and laboratory finding will be followed.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Sao Paulo General Hospital
• Treatments: Methotrexate

Criteria

Inclusion Criteria:

• Multi-vessels coronary artery disease diagnosis by coronary CT or invasive angiography

• Aortic atherosclerosis diagnosis by multidetector computed tomography (MDCT) angiography.

• High-sensitivity C reactive protein (hs-CRP) levels > 2mg/L

• Signing the study informed consent.

Exclusion Criteria:

• History of Acute myocardial infarction in the last 30 days

• Heart failure with ejection fraction <40%

• Estimated glomerular filtration rate < 40 mL/min/1.73 m2.

• Prior history of chronic infectious disease, including tuberculosis, severe fungal disease, or known HIV positive.

• Chronic hepatitis B or C infection.

• Prior history of nonbasal cell malignancy or myeloproliferative or lymphoproliferative disease within the past 5 years.

• White blood cell count <4000/mm3, hematocrit <32%, or platelet count <75000/mm3.

• Alanine aminotransferase levels (ALT) greater than 3-fold the upper limit of normal.

• History of actual alcohol abuse or unwillingness to limit alcohol consumption to < 4 drinks per week.

• Pregnancy or breastfeeding.

• Women of child bearing potential, even if currently using contraception.

• Men who plan to father children during the study period or who are unwilling to use contraception.

• Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers.

• Known chronic pericardial effusion, pleural effusion, or ascites.

• Angina pectoris Canadian Cardiovascular Society (CCS) III-IV

• New York Heart Association class III-IV congestive heart failure.

• Contraindication for the use of iodinated contrast

• Life expectancy of < 1 years.

• Acute or Chronic aortic dissection

• Interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis.

• Current indication for methotrexate therapy.

• Patient with a history of an allergic reaction or significant sensitivity to methotrexate.

• Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazole) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible.