The Impact of IV Iron on Exercise Capacity and Quality of Life in Pulmonary Hypertension

Prior treatment

• Treatment with oral or other IV iron therapies at screening.
• Any planned surgery or procedure leading to expected significant blood loss (defined as more than 250 ml = equal to 125mg of iron).
• Concurrently in a study with another investigational product.

Other illness

• Known hypersensitivity reaction to any component of FCM
• Group 1 PH associated with veno-occlusive diseases.
• Current or planned mechanical circulatory support or lung/heart transplantation.
• Active infection as judged by the investigator.

Lab values

• Screening haemoglobin \< 8 g/dl or \>15 g/dl

Other

• Ferritin \> 700 ng/mL
• Primary diagnosis of group 3 PH
• Primary diagnosis of group 5 PH
• Haemodialysis or peritoneal dialysis (current or planned within the next 24 weeks).
• Inability to return for follow up visits within the necessary windows
• Uncorrected moderate to severe aortic stenosis (AVA \<1.5cm² and mean gradient \>20 mmHg) or severe valvular regurgitation (except tricuspid regurgitation)
• Impression by investigator that patient cannot perform a 6MWT
• Pregnancy or desire to become pregnant during the study duration.

• ≥18 years of age
• WHO functional class II - IV
• Iron deficiency defined as TSAT \<21% (no more than ≥3 months old at randomization)
• PH defined by echocardiography and/or right heart catheterization (RHC) according to the following WHO groups:
  • Group 1 PH:
  • Patients with a diagnosis of idiopathic PAH, hereditary PAH, drug induced PAH or PAH and associated with CTD or CHD (historical RHC available) on stable and optimized doses of PAH targeted therapies for at least 4 weeks before randomization.
  • Echocardiographic evidence of a high or intermediate probability for PH as per 2022 ESC PH guidelines.
  • Group 2 PH and baseline LVEF \> 50% on imaging modality within last 6 months before randomization and on stable doses of loop diuretics and HFpEF therapies for 4 weeks. Group 2 PH can be included based on echocardiography or RHC.:
  • Echocardiography (\<6mo before randomization):
  • Presence of LVH or LA-enlargement
  • E/e' \>15 (at rest or exercise)
  • TRVmax \>2.8 m/s (at rest) or mPAP/CO\>3 mHg/L/min (exercise) or echocardiographic evidence of high or intermediate probability for PH as per 2022 ESC PH guidelines.
  • RHC (\<6mo before randomization)
  • mPAP \> 20 mmHg
  • PCWP \> 15 mmHg at rest or PCWP/CO-slope \> 2mmHg/L/min or exercise PCWP\>25mmHg, or PCWP 13-15 mmHg with elevation ≥18mmHg after 500 cc Fluid Challenge
  • Group 4 PH:
  • Inoperable CTEPH
  • Persistent/recurrent CTEPH (\> 1 year after endarterectomy or \> 6 months after balloon pulmonary angioplasty) ineligible for balloon pulmonary angioplasty.
  • Echocardiographic evidence of a high or intermediate probability for PH as per 2022 ESC PH guidelines.