The clinical trial No. REFRANGINA-TRIAL protocol is aimed at dynamic assessment of myocardial perfusion and contractility in patients with refractory angina under combined intermittent hypo-hyperoxic therapy. Refractory angina characterized by persistent symptoms and impaired functional status despite optimal medical treatment, as well as ineffective invasive revascularization affects 5—10% of patients with coronary artery disease. The study will enroll 60 patients with coronary artery disease and refractory angina class II—III confirmed by stress tests. Patients will be randomized into three groups: group 1 — combined therapy (10 sessions of intermittent hypo-hyperoxic therapy over 2 weeks and 5-week medical therapy beginning 3 weeks prior to hypo-hyperoxic sessions); group 2 — a course of hypo-hyperoxic therapy with placebo (10 sessions over 2 weeks); group 3 — standard treatment according to current protocol. Treatment efficacy will be evaluated using contrast-enhanced perfusion MRI, echocardiography (with measurement of ejection fraction and global longitudinal strain of the left ventricle), stress tests (treadmill test and 6-minute walk test), as well as assessment of endothelial function by NICaS method and quality of life (SF-36 questionnaire). Treatment safety will be monitored through regular checks of vital signs, ECGs, laboratory tests, and physical examinations, along with recording of adverse events. The study is conducted in strict accordance with the Declaration of Helsinki, legislation of the Russian Federation, and Good Clinical Practice standards (ICH-GCP). It is anticipated that final results will confirm safety and efficacy of this new non-invasive approach for treating refractory angina. This will optimize therapeutic strategies and update clinical guidelines in the Russian Federation.