Impact of Intravenous Iron Repletion On Mechanisms of Exercise InTolerance in HFpEF (IRONMET-HFpEF)

Korábbi kezelés

• Planned surgical procedure during the trial period 13. Inability to return for follow up visits

Más betegség

• Known hypersensitivity reaction to any component of ferric derisomaltose (Monofer®)
• History of acquired iron overload (e.g. hemochromatosis), or the recent receipt (within 3 months) of erythropoietin stimulating agent, IV iron therapy, or blood transfusion.
• Documented active gastrointestinal bleeding
• Anemia with known cause other than iron deficiency or chronic disease
• Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 3 months of enrollment.
  • 7 Presence of any condition that precludes exercise testing such as:

Laborértékek

• Claudication that limits exertion b. Uncontrolled bradyarrhythmia or tachyarrhythmia (according to Investigator judgment, pacemaker treatment is allowed as long as the same pacing mode/activity can be used at baseline and follow-up CPET) c. Clinically significant musculoskeletal disease or orthopedic conditions that limit the ability to perform the CPET (e.g., arthritis or injury in the foot, leg, knee or hip) d. Severe obesity (BMI > 50.0 kg/m2) e. Any other non-heart failure condition that, in the opinion of the Investigator, that is the primary limitation to exercise. 8. Severe renal dysfunction (eGFR< 20 ml/min/1.73m2) 9. Severe liver disease (ALT or AST > 3x upper limit of normal, alkaline phosphatase or bilirubin >2x upper limit of normal) 10. Active malignancy other than non-melanoma skin cancers 11. Female participant of child-bearing potential who is pregnant, lactating, or not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.

Egyéb

• Current or planned intravenous iron supplementation. Iron-containing multivitamins (<30 mgs /day) are permitted.

• Adult (≥18 years of age) able to provide informed consent.
• Stable heart failure (NYHA II-IV) for at least 4 weeks
• Heart Failure with Preserved left ventricular ejection fraction.(Left ventricular ejection fraction ≥ 50 % obtained within 6 months of informed consent.
• NT-proBNP ≥ 125 pg/mL without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at the time of sample collection, NT-proBNP must be ≥ 250 pg/mL OR patients must have a history of pulmonary capillary wedge pressure ≥ 15 mm Hg during rest or the slope of pulmonary capillary wedge pressure to cardiac output (PCWP/CO) ≥ 2.0 mmHg/L/min during upright exercise (Eisman et al., Circ Heart Fail. 2018 May;11(5):e004750.).OR subjects must have a heart failure hospitalization within the last 12 months prior to screening OR Chronic diastolic dysfunction on echocardiography as evidenced by: Left Atrial Enlargement (LAE): LA diameter ≥ 3.8cm in women, ≥ 4.0 cm in men or LA length ≥ 5.0 cm or LA area ≥ 20 cm2 OR LA volume ≥ 55mL or LA volume index ≥ 29ml/m2 or Left Ventricular Hypertrophy (LVH): septal thickness or posterior wall thickness ≥ 1.1 cm OR For patients in sinus rhythm: E/e' ratio ≥15 at septal annulus, or E/e' ratio ³13 at lateral annulus, or average E/e' ratio ³14. For patients in atrial fibrillation: E/e' ≥ 11 at the septal annulus.
• Hemoglobin >9.0 g/dL AND <15.0 g/dL .
• Serum ferritin <100 ng/mL OR 100 to 300 ng/mL with TSAT <20%, but NOT ferritin < 15 ng/mL.
• Demonstrate diminished exercise capacity: ≤ 75 % predicted peak VO2 as determined by a Cardiopulmonary Exercise Test (CPET) at the time of screening
• Perform a maximal effort CPET by achieving a Respiratory Exchange Ratio (RER) of ≥ 1.05