What is the effect of intravenous iron supplementation on cardiopulmonary haemodynamics, exercise capacity and quality of life in patients with IPAH and iron deficiency?

• Register: EUCTR
• Last refreshed on: 26 March 2018
• Main ID: EUCTR2010-024585-22-DE
• Date of registration: 17/08/2016
• Prospective Registration: Yes
• Primary sponsor: Imperial College Academic Healthsciences Centre
• Public title: What is the effect of intravenous iron supplementation on cardiopulmonary haemodynamics, exercise capacity and quality of life in patients with IPAH and iron deficiency?
• Scientific title: What is the effect of intravenous iron supplementation on cardiopulmonary haemodynamics, exercise capacity and quality of life in patients with IPAH and iron deficiency? - Ferinject® for iron deficiency in IPAH patients
• Date of first enrolment: 01/12/2016
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024585-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, United Kingdom

Contacts

• Name: Vijaykumar Zala
• Affiliation: NIHR/Wellcome Trust Imperial Clinical Research Facility, Imperial Centre for Translational and Experimental Medicine

• Name: Vijaykumar Zala
• Affiliation: NIHR/Wellcome Trust Imperial Clinical Research Facility, Imperial Centre for Translational and Experimental Medicine

Key inclusion & exclusion criteria

Inclusion criteria:
The following entry criteria have to be chosen carefully 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 anorexigens.
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 < 37 ug/l; transferrin saturations < 16.4%; iron < 10.3 umol/l.
4. Documented diagnosis of PAH by right heart catheterisation performed at any time prior to Screening showing: resting mean pulmonary artery pressure >25mmHg, pulmonary capillary wedge pressure =/< 15 mm Hg and normal or reduced cardiac output;
5. 6 minute walking distance greater than 50m at entry;
6. Stable on an unchanged PAH therapeutic regime (any combination of endothelin receptor antagonist, phosphodiesterase inhibitor or prostacyclin analogue) for at least 1 month.
7. Able to provide written informed consent prior to any study-mandated procedures
8. Female subjects of child-bearing potential are eligible to participate if they agree to use one of the following contraception methods:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
o oral
o injectable
o implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner
• Sexual abstinence

Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Unable to provide informed consent.
2. Clinically-significant renal disease (Creatinine clearance < 30 ml/min per 1.73 m2 calculated from CKD-Epi
http://www.qxmed.com/renal/Calculate-CKD-EPI-GFR.php) or liver disease (including serum transaminases > 3 times upper limit of normal).
3. Haemoglobin concentration <10 g/dl.
4. Patients will be excluded if any single parameter (iron, ferritin or transferritin saturation) exceeds 1x upper limit of normal (ULN) in the local lab reference range
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 as judged by the investigator
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 Creutzfeld-Jakob disease.
13. Known hypersensitivity to FerinjectP®P or any of its excipients and any other iron supplement preparation.
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Idiopathic or familial pulmonary arterial hypertension
MedDRA version: 19.0 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Ferinject
Product Name: Ferinject
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: FERRIC CARBOXYMALTOSE
CAS Number: 9007-72-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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 noninvasive 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).

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.

Primary end point(s): Endurance time at the end of endurance bicycle cardiopulmonary exercise testing at 80% peak work rate determined from the incremental exercise test

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

Secondary end point(s): • Incremental bicycle cardiopulmonary exercise testing - peak VO2 (ml/min/kg), VO2 at metabolic threshold, VE/VCO2 slope, V02/WR slope and 02 pulse.
• VO2 at the end of endurance bicycle cardiopulmonary exercise testing at 80% peak work rate determined from the incremental exercise test
• Gas exchange at 3 minutes after the start of the work phase of an endurance exercise test at 80% peak work rate determined from the incremental exercise test
• 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 sites where facility is available)

Timepoint(s) of evaluation of this end point: 24 weeks

Secondary ID(s)

WILK3

2010-024585-22-GB

Source(s) of Monetary Support

British Heart Foundation