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

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2010-024585-22-GB
• Lead Sponsor: Imperial College Academic Healthsciences Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-02-25
• Study Completion: 2017-12-22
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 39

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 < 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. Six minute walking distance greater than 150m 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:
- Abstinence
- Contraceptive methods with a failure rate of < 1%:
- Oral contraceptive, either combined or progestogen alone;
- Injectable progestogen;
- Implants of levonorgestrel;
- Estrogenic vaginal ring;
- Percutaneous contraceptive patches;
- Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure rate as stated in the product label;
- Male partner(s) sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study;
- Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus vaginal spermicidal agent (foam/gel/film/cream/suppository).

*Patients who have not had a cardiac catheterisation prior to screening, but meet all other inclusion/exclusion criteria will be considered for the study if the clinical diagnosis is in keeping with idiopathic pulmonary arterial hypertension (IPAH). Inclusion of such patients should be discussed with the CI. These patients will be excluded at baseline if during the right heart catheterisation (RHC) the following criteria are not met: resting mean pulmonary artery pressure > 25mm Hg, pulmonary capillary wedge pressure =/< 15 mm Hg and normal or reduced cardiac output.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
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 who meet any of the following criteria will be excluded:
Iron>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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified