The Impact of IV Iron on Exercise Capacity and Quality of Life in Pulmonary Hypertension (IRON-PH)

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

Pulmonary hypertension (PH) is a condition characterized by elevated blood pressure in the pulmonary arteries. This leads to symptoms such as shortness of breath and a significantly reduced exercise capacity, resulting in a very poor quality of life. Currently, treatment options for PH are limited.

More than 60% of patients with PH develop iron deficiency. Studies have shown that this deficiency is associated with more severe symptoms, reduced exercise capacity, and even lower quality of life. Oral iron supplements are often ineffective in these patients due to impaired absorption in the intestines, caused by chronic low-grade inflammation-a common feature in PH.

Intravenous iron administration can rapidly correct the deficiency, but it remains unclear whether this also leads to clinical improvements such as enhanced exercise capacity, reduced shortness of breath, and improved quality of life. Moreover, the cost-effectiveness of this treatment is still unknown. The IRON-PH study aims to answer these questions.

As part of the IRON-PH study, 306 patients with pulmonary hypertension will be enrolled. Each patient will be randomized to receive either intravenous iron (ferric carboxymaltose) or intravenous placebo (NaCl 0.9%).

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Hypertension; Iron Deficiency
• Intervention / Treatment: Drug: Ferric Carboxymaltose (FCM); Drug: Sodium Chloride (NaCl) 0.9 %

• Study Type: Interventional
• Enrollment (Estimated): 306
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Not yet recruiting
    • AZORG
    • Contact: Kathy De Knijf; Phone Number: +3253724449; Email: kathy.de.knijf@AZORG.be
    • Principal Investigator: Jeroen Dauw
  • Brussels, Belgium, 1070
    • Not yet recruiting
    • Hôpital Erasme
    • Principal Investigator: Jean-Luc Vachiery
    • Contact: Frederic Gayet; Phone Number: +3225558106; Email: frederic.gayet@hubruxelles.be
  • Genk, Belgium, 3600
    • Recruiting
    • Ziekenhuis Oost-Limburg
    • Principal Investigator: Pieter Martens
    • Contact: Julie Bollen; Phone Number: +3289807251; Email: julie.bollen@zol.be
  • Kortrijk, Belgium, 8500
    • Not yet recruiting
    • AZ Groeninge
    • Principal Investigator: Mathias Leys
    • Contact: Helena Vandenbroeke; Phone Number: +3256636353; Email: studieslongziekten@azgroeninge.be
  • Leuven, Belgium, 3000
    • Not yet recruiting
    • UZ Leuven
    • Principal Investigator: Marion Delcroix
    • Contact: Margo Vangrunderbeek; Phone Number: +3216346842; Email: margo.vangrunderbeek@uzleuven.be
  • Lodelinsart, Belgium, 6042
    • Not yet recruiting
    • CHU Charleroi-Chimay
    • Contact: Aya El Houri; Phone Number: +3271922249; Email: aya.elhouri@humani.be
    • Principal Investigator: Simina Ciurica
  • Yvoir, Belgium, 5530
    • Not yet recruiting
    • Chu Ucl Namur
    • Contact: Fabien Dormal; Phone Number: +3281423658; Email: fabien.dormal@chuuclnamur.uclouvain.be
    • Principal Investigator: Fabian Demeure

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Sodium Chloride (NaCl) 0.9 %; Placebo, dosing and administration according to SmPC guidelines
Experimental: Ferric carboxymaltose	Drug: Ferric Carboxymaltose (FCM); Ferric Carboxymaltose (FCM), dosing and administration according to SmPC guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6MWD	Change in 6-minute walking distance (6MWD) from baseline to 24 week follow-up	From baseline to 24 week follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MLHFQ	Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score from baseline to 24 week follow-up. Total Score: Sum of all 21 items (0-105) Higher Score = Worse QoL: A higher number indicates a greater negative impact from heart failure Lower Score = Better QoL: A lower score suggests less limitation	Baseline to 24 week follow-up
Change in EQ5D5L	Change in EuroQol 5 dimensions - 5 levels questionnaire score from baseline to 24 week follow-up EQ-5D-5L combiines responses from five health dimensions, each with five severity levels to create a 5-digit health state code, then applying country-specific "value sets" (valuation matrices) to convert this code into a single Index Score (Utility Score), ranging from <0 (worst) to 1 (best health), plus a separate EQ-VAS score (0-100) for overall self-rated health. Dimensions: Mobility, self-care, usual activities, pain/discomfort, anxiey/depression Levels: 1 no problem, 2 slight problems, 3 moderate problems, 4 severe problems, 5 unable to/extreme problems Example of 5-digit state code: 12345 indicates no problems with mobility, slight problems with self-care, moderate problems with usual activities, severe pain/discomfort and extreme anxiety/depression	Baseline to 24 week follow-up
Change in FSS	Change in Fatigue Severity Scale (FSS) score from baseline to 24 weeks Total score: sum of all scores (ranging between 9 - 63) Higher Scores = More Fatigue Lower Scores = Less Fatigue	Baseline to 24 week follow-up
Developing composite clinical worsening event	The hazard ratio between treatment arms in developing the composite clinical worsening event in the overall trial population	From first patient Day 1 (Baseline) to study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Ziekenhuis Oost-Limburg
• Collaborators: Federal Knowledge Centre (KCE)

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: January 21, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Respiratory Tract Diseases; Lung Diseases; Iron Metabolism Disorders; Hypertension; Nutritional and Metabolic Diseases; Iron Deficiencies; Hypertension, Pulmonary; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride; ferric carboxymaltose
• Other Study ID Numbers: Z-2025090; 2025-522936-14-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No