Intravenous iron to improve exercise capacity and quality of life in pulmonary hypertension

A Randomized, Double-blind, Placebo-controlled, Multicentre Trial, Assessing the Impact of Ferric Carboxymaltose on Exercise Capacity and Functional Status in Pulmonary Hypertension

This trial will test whether intravenous ferric carboxymaltose can improve exercise ability and quality of life in adults with pulmonary hypertension who have iron deficiency.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 306 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ziekenhuis Oost-Limburg (other)
• Locations: 7 sites (Aalst and 6 other locations)
• Trial ID: NCT07359599 on ClinicalTrials.gov

What this trial studies

The study enrolls adults with pulmonary hypertension and iron deficiency (TSAT <21%) and randomizes them to receive intravenous ferric carboxymaltose or saline placebo at specialized Belgian centers. Participants must be WHO functional class II–IV and on stable background therapies where applicable. Outcomes include changes in exercise capacity measured by standardized exercise tests, symptom burden, validated quality-of-life questionnaires, and health economic analyses of cost-effectiveness. Blood iron indices and clinical follow-up visits are performed to monitor response and safety.

Who should consider this trial

Good fit: Adults (≥18) with pulmonary hypertension and documented iron deficiency (TSAT <21%) in WHO functional class II–IV who are stable on PH therapies and able to attend Belgian study sites are ideal candidates.

Not a fit: Patients without iron deficiency, those whose symptoms are primarily due to non-iron-related causes, or those unable to receive IV iron (for example due to allergy) are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, intravenous iron could rapidly correct deficiency and lead to better exercise tolerance, less breathlessness, and improved quality of life for people with pulmonary hypertension.

How similar studies have performed: Intravenous iron has shown benefit for symptoms and exercise capacity in heart failure trials, but evidence specifically in pulmonary hypertension is limited, making this approach partly supported by related-condition data.

Eligibility criteria

Inclusion Criteria:

* ≥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.

Exclusion Criteria:

* Screening haemoglobin \< 8 g/dl or \>15 g/dl
* Ferritin \> 700 ng/mL
* Known hypersensitivity reaction to any component of FCM
* Group 1 PH associated with veno-occlusive diseases.
* Primary diagnosis of group 3 PH
* Primary diagnosis of group 5 PH
* Treatment with oral or other IV iron therapies at screening.
* Current or planned mechanical circulatory support or lung/heart transplantation.
* Any planned surgery or procedure leading to expected significant blood loss (defined as more than 250 ml = equal to 125mg of iron).
* Haemodialysis or peritoneal dialysis (current or planned within the next 24 weeks).
* Inability to return for follow up visits within the necessary windows
* Concurrently in a study with another investigational product.
* 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
* Active infection as judged by the investigator.
* Pregnancy or desire to become pregnant during the study duration.

Where this trial is running

Aalst and 6 other locations

• AZORG — Aalst, Belgium (NOT_YET_RECRUITING)
• Hôpital Erasme — Brussels, Belgium (NOT_YET_RECRUITING)
• Ziekenhuis Oost-Limburg — Genk, Belgium (RECRUITING)
• AZ Groeninge — Kortrijk, Belgium (NOT_YET_RECRUITING)
• UZ Leuven — Leuven, Belgium (NOT_YET_RECRUITING)
• CHU Charleroi-Chimay — Lodelinsart, Belgium (NOT_YET_RECRUITING)
• CHU UCL Namur — Yvoir, Belgium (NOT_YET_RECRUITING)

Conditions: Pulmonary Hypertension, Iron Deficiency