ORal IrON Supplementation With Ferric Maltol in Patients With Pulmonary Hypertension (ORION-PH-1)

Study Overview
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Brief Summary
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This is an explorative, open-label, uncontrolled, single center study to explore the preliminary safety, tolerability and efficacy of oral ferric maltol in treating iron deficiency in patients with pulmonary hypertension and iron deficiency anemia.

Official Title
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A Pilot Study to Explore Preliminary Safety, Tolerability and Efficacy of ORal IrON Supplementation With Ferric Maltol in Treating Iron Deficiency in Patients With Pulmonary Hypertension and Iron Deficiency Anemia

Conditions
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Hypertension, Pulmonary, Anemia, Iron Deficiency

Intervention / Treatment
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* Drug: Ferric maltol 30 mg (Feraccru®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent prior to any study-related procedure and willingness to comply with treatment and follow-up procedures Male and female patients ≥18 years at day of inclusion Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial Patients with a diagnosis of PH confirmed by a (historical) right heart catheterization showing a mean pulmonary artery pressure ≥25 mmHg at rest and stable PH medication for at least 3 months. 6 min walk distance >50 m Mild-to-moderate iron-deficiency anemia as defined by a hemoglobin concentration ≥7 g/dl and <12 g/dl in females or ≥8 g/dl and <13 g/dl in males, and serum ferritin <100 µg/l, or 100-300 µg/l and transferrin saturation <20% at screening Prevention of pregnancy: Women without childbearing potential defined as follows: at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or hysterectomy or uterine agenesis or ≥ 50 years and in postmenopausal state ≥ 1 year or < 50 years and in postmenopausal state ≥ 1 year with serum FSH > 40 IU/l and serum oestrogen < 30 ng/l or a negative oestrogen test or Women of childbearing potential with a negative ß-HCG pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of four weeks following the last administration of study medication: correct use of contraception methods. The following are acceptable: hormonal contraceptives (combined oral contraceptives and oestrogen-free pills with desogestrel, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUS) or a barrier method, e.g. condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide (foam, gel, film, cream or suppository) true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception) sexual relationship only with female partners and/or sterile male partners Exclusion Criteria: Active hematological disorders other than iron-deficiency anemia Other medical condition that according to the investigator's assessment is causing or contributing to anemia Active malignancy Active infectious disease Active bleeding Severe renal insufficiency (glomerular filtration rate <30 ml/min) Severe liver injury as indicated by serum aminotransferases >3 x upper limit of normal or bilirubin levels >50 µmol/l Ongoing oral or intravenous iron supplementation Hemoglobin <7 g/dl in females or <8 g/dl in males at screening Concomitant erythropoietin medication Pregnancy or lactation period Subject has received any investigational medication or any investigational device within 30 days prior to the first dose of study medication or is actively participating in any investigational drug/devices trial, or is scheduled to receive an investigational drug/device during the course of the study. Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal product Known haemochromatosis or other iron overload syndromes Patients who have been receiving repeated (>1) blood transfusions during the past 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Explorative, open-label, uncontrolled monocenter study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferric maltol 30 mg (Feraccru®)<br>Treatment with Feraccru® 30 mg hard capsules (Ferric maltol 30 mg). One capsule twice daily, morning and evening, on an empty stomach for 12 weeks | Drug: Ferric maltol 30 mg (Feraccru®)<br>* Feraccru® 30 mg hard capsules will be used. Each capsule contains 30 mg iron (as ferric maltol), 91.5 mg of lactose, 0.5 mg of Allura Red AC (E129) and 0.3 mg Sunset Yellow FCF (E110) as excipients with known effects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin level from baseline to week 12 | measurement of hemoglobin in blood | baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin from baseline to week 6 | measurement of hemoglobin in blood | baseline to week 6 | 
| Change in serum ferritin levels from baseline to week 6 and 12 | measurement of serum ferritin levels | baseline to week 6 and baseline to week 12 | 
| Change in transferrin saturation from baseline to week 6 and 12 | measurement of transferrin saturation | baseline to week 6 and baseline to week 12 | 
| Change in 6 min walking distance from baseline to week 12 | measurement of functional exercise capacity | baseline to week 12 | 
| Change in serum NT-proBNP from baseline to weeks 6 and 12 | measurement of serum NT-proBNP | baseline to week 6 and baseline to week 12 | 
| Change in echocardiographic markers of right ventricular function from baseline to week 12 (1) | measurement of right atrial area | from baseline to week 12 | 
| Change in echocardiographic markers of right ventricular function from baseline to week 12 (2) | measurement of right ventricular diameter | from baseline to week 12 | 
| Change in echocardiographic markers of right ventricular function from baseline to week 12 (3) | measurement of fractional area change | from baseline to week 12 | 
| Change in echocardiographic markers of right ventricular function from baseline to week 12 (4) | measurement of tricuspid annular plane systolic excursion | from baseline to week 12 | 
| Change in World Health Organization Functional Class (WHO FC) from baseline to week 6 and week 12 | measurement of different parameter according to an evaluated process | from baseline to week 6 and week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension, Iron Deficiency