Idiopathic or familial pulmonary arterial hypertension MedDRA version: 18.0 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Ferinject
Product Name: Ferinject
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Ferric carboxymaltose
Conc
Sponsors
Imperial College Academic Healthsciences Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: We have carefully chosen the following entry criteria to clearly define our study group and reduce the potential for variation. 1. Males or females aged between 16–75 years old 2. PAH which is idiopathic, heritable or associated with anorexogens. 3. Iron deficiency as defined by any one of the following criteria: sTfR levels > 28.1 nmol/l (where sTfR analysis is available) or one of the following: Ferritin 25mmHg, pulmonary capillary wedge pressure =/ 25mm Hg, pulmonary capillary wedge pressure =/=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Unable to provide informed consent. 2. Clinically-significant renal disease (Creatinine clearance 3 times upper limit of normal). 3. Haemoglobin concentration 27 umol/L, Ferritin>300 ug/L or Transferrin saturations >45% 5. Patients with moderate to severe hypophosphatemia as defined as <0.65mmol/L 6. Known to have haemoglobinopathy e.g. sickle cell disease, thalassaemia. 7. Admission to hospital related to PAH or change in PAH therapy within 1 month prior to Screening. 8. Evidence of left ventricular disease or significant lung disease on high-resolution CT scanning or lung function. 9. Acute or chronic infection or inflammation. 10. Significant uncontrolled asthma as judged by the investigator, eczema or atopic allergies. 11. Females who are lactating or pregnant. 12. Individuals known to have HIV, Hepatitis B or C or Creutzfeldt-Jakob disease. 13. Known hypersensitivity to Ferinject® or any of its excipients. 14. Evidence of disturbances in utilisation of iron. 15. Significant blood loss (e.g. GI bleed) within the last 3 months or history of menorrhagia. 16. Unable to perform a Cardiopulmonary Exercise Test i.e. due to syncope or musculoskeletal factors. 17. Patients who have received an investigational medicinal product within 30 days of entering the baseline visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the clinical value of using intravenous iron (ferric carboxymaltose) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension. The primary endpoint will be the change in the resistance to blood flow through the lungs (resting pulmonary vascular resistance), measured by cardiac catheterisation at baseline and 12 weeks after the initial infusion. ;Secondary Objective: It is possible that iron may have beneficial effects via mechanisms not directly related to the blood flow through the lungs. Capturing other data, particularly exercise capacity, on the study participants is therefore essential. These non-invasive tests will be repeated to detect evidence of early benefit (at 2 weeks) as well as to follow serial changes in exercise capacity and iron status (at 12, 14, and 24 weeks after the initial infusion).;Primary end point(s): The change in resting pulmonary vascular resistance (PVR) between baseline and 12 weeks, measured by cardiac catheterisation. ;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incremental bicycle cardiopulmonary exercise testing - peak VO2 (ml/min/kg), VO2 at metabolic threshold, VE/VCO2 slope, VO2/WR slope, O2 pulse and tissue oxygenation index (at Hammersmith Site). • Endurance time on bicycle cardiopulmonary exercise test at 80% peak work rate, with measurement of steady-state gas exchange and tissue oxygenation index (Hammersmith Site only) at 3 minutes and peak • Resting cardiopulmonary haemodynamics – right atrial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output and stroke volume • Exercise cardiopulmonary haemodynamics (at a work rate equivalent to 40% peak VO2) - pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output and stroke volume • Iron indices – serum iron, transferrin saturations, ferritin, soluble transferrin receptor (sTfR), unsaturated iron binding capacity (UIBC), red cell distribution width (RDW) and erythropoietin (EPO) levels • 6 minute walk distance and Borg dyspnoea scale • NYHA WHO functional class • NT-pro-BNP • Quality of life (CAMPHOR questionnaire) and the self-reported Patient Global Assessment • Safety - the occurrence of adverse events • Cardiac MRI - right ventricular volumes, mass, ejection fraction, stroke volume and diastolic function (at Hammersmith and Sheffield only) ;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Countries
Germany, United Kingdom
Outcome results
None listed