IV Iron Replacement for Iron Deficiency in Idiopathic Pulmonary Arterial Hypertension (IPAH) Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01447628
• Date of registration: 04/10/2011
• Prospective Registration: No
• Primary sponsor: Imperial College London
• Public title: IV Iron Replacement for Iron Deficiency in Idiopathic Pulmonary Arterial Hypertension (IPAH) Patients
• 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?
• Date of first enrolment: October 2011
• Target sample size: 40
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01447628
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

China, Germany, United Kingdom

Contacts

• Name: Luke Howard, DPhil, FRCP
• Affiliation: Imperial College London

Key inclusion & exclusion criteria

- Males or females aged between 16-75 years old

- PAH which is idiopathic, heritable or associated with anorexigens.

- Iron deficiency (TfR levels > 28.1 nmol/l, where sTfR analysis is available, Ferritin
< 37 ug/l; transferrin saturations < 16.4%; iron < 10.3 umol/l)

- 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;

- 6 minute walking distance greater than 50m at entry;

- Stable on an unchanged PAH therapeutic regime (any combination of endothelin receptor
antagonist, phosphodiesterase inhibitor or prostacyclin analogue) for at least 1
month.

- Able to provide written informed consent prior to any study-mandated procedures

- 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).

Exclusion criteria

- Unable to provide informed consent.

- 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).

- Haemoglobin concentration <10 g/dl.

- Patients will be excluded if any single parameter (iron, ferritin or transferrin
saturation) exceeds 1x upper limit of normal (ULN) in the local lab reference range.

- Patients with moderate to severe hypophosphatemia as defined as <0.65mmol/L

- Known to have haemoglobinopathy e.g. sickle cell disease, thalassaemia.

- Admission to hospital related to PAH or change in PAH therapy within 1 month prior to
Screening.

- Evidence of left ventricular disease or significant lung disease on high-resolution CT
scanning or lung function as judged by the investigator

- Acute or chronic infection or inflammation.

- Significant uncontrolled asthma as judged by the investigator, eczema or atopic
allergies.

- Females who are lactating or pregnant.

- Individuals known to have HIV, Hepatitis B or C or Creutzfeld-Jakob disease.

- Known hypersensitivity to Ferinject® or any of its excipients.

- Evidence of disturbances in utilisation of iron.

- Significant blood loss (e.g. GI bleed) within the last 3 months or history of
menorrhagia.

- Unable to perform a Cardiopulmonary Exercise Test i.e. due to syncope or
musculoskeletal factors.

- Patients who have received an investigational medicinal product within 30 days of
entering the baseline visit



Age minimum: 16 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Iron Deficiency

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Saline

Drug: Ferinject or CosmoFer

Primary Outcome(s)

Change in Exercise Capacity - Endurance [Time Frame: 12 Weeks post study treatment]

Change in resting pulmonary vascular resistance (PVR) [Time Frame: 12 weeks from baseline]

Secondary Outcome(s)

Cardiac MRI [Time Frame: 12 weeks post study treatment]

WHO functional class [Time Frame: 12 weeks post study treatment]

Difference in exercise capacity - Incremental [Time Frame: 12 weeks post study treatment]

NT-proBNP [Time Frame: 12 weeks post study treatment]

Iron indices [Time Frame: 12 weeks post study treatment]

Safety - In terms of reported adverse events [Time Frame: 12 weeks post study treatment]

6 minute walk distance and Borg dyspnoea scale [Time Frame: 12 weeks post study treatment]

Difference in gas exchange at 3 minutes [Time Frame: 12 weeks post study treatment]

Quality of life assess by questionnaire [Time Frame: 12 weeks post study treatment]

Secondary ID(s)

CRO1811

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Fu Wai Hospital, Beijing, China