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

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ClinicalTrials.gov Identifier: NCT01447628
Recruitment Status : Recruiting
First Posted : October 6, 2011
Last Update Posted : January 30, 2018
Sponsor:
Collaborator:
Fu Wai Hospital, Beijing, China
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

This study will establish whether intravenous iron replacement has clinical benefit in idiopathic pulmonary arterial hypertension.

A 24-week double-blind, randomised, placebo-controlled, crossover study will investigate whether a single dose of 1g of Ferinject® or CosmoFer improves cardiopulmonary haemodynamics, exercise capacity and quality of life and is well-tolerated.


Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Iron Deficiency Drug: Saline Drug: Ferinject or CosmoFer Phase 2

Detailed Description:
IV iron formulation used in Europe - Ferinject IV iron formulation used in China - CosmoFer

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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?
Study Start Date : October 2011
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Active Comparator: Ferinject or CosmoFer

IV iron formulation used in Europe - Ferinject - given over 15 minutes

IV iron formulation used in China - CosmoFer - over a period of 4 to 6 hours

Drug: Ferinject or CosmoFer
Intravenous, 1000 mg iron
Placebo Comparator: Saline Drug: Saline
intravenous, no active drug



Primary Outcome Measures :
  1. Change in resting pulmonary vascular resistance (PVR) [ Time Frame: 12 weeks from baseline ]
    To be measured by cardiac catheterisation in wood units.

  2. Change in Exercise Capacity - Endurance [ Time Frame: 12 Weeks post study treatment ]
    Endurance time at the end of the endurance bicycle cardiopulmonary exercise testing at 80% peak work rate determined from the incremental exercise test


Secondary Outcome Measures :
  1. Difference in exercise capacity - Incremental [ Time Frame: 12 weeks post study treatment ]
    Incremental bicycle cardiopulmonary exercise testing - peak VO2 (ml/min/kg), VO2 at metabolic threshold, VE/VCO2 slope, VO2/WR slope and O2 pulse

  2. Iron indices [ Time Frame: 12 weeks post study treatment ]
    Iron indices - serum iron, transferrin saturations, ferritin, soluble transferrin receptor, RDW, EPO, and UIBC

  3. Cardiac MRI [ Time Frame: 12 weeks post study treatment ]
    Cardiac MRI - right ventricular volumes, mass, ejection fraction, stroke volume and diastolic function (reported in mL)

  4. 6 minute walk distance and Borg dyspnoea scale [ Time Frame: 12 weeks post study treatment ]
    6 minute walk distance (meters) and Borg dyspnoea scale (from 1-10)

  5. WHO functional class [ Time Frame: 12 weeks post study treatment ]
    WHO Functional Class (I-IV)

  6. NT-proBNP [ Time Frame: 12 weeks post study treatment ]
    Change in NT-proBNP (fmol/ml)

  7. Quality of life [ Time Frame: 12 weeks post study treatment ]
    Quality of life (CAMPHOR questionnaire) and the self-reported Patient Global Assessment

  8. Safety - In terms of reported adverse events [ Time Frame: 12 weeks post study treatment ]
    Safety - the number, occurrence and frequency of adverse events

  9. Difference in gas exchange at 3 minutes [ Time Frame: 12 weeks post study treatment ]
    Gas exchange at 3 minutes from an endurance exercise test at 80% peak work rate determined from the incremental exercise test



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Ages Eligible for Study:   16 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  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:

    • 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

  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 transferrin 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01447628


Contacts
Contact: Luke Howard, DPhil, FRCP 020 8383 3171 l.howard@imperial.ac.uk
Contact: Vijay Zala, M.Pharm, MBA 020 8383 6103 V.Zala@imperial.ac.uk

Locations
China
Fuwai Hospital Recruiting
Beijing, China
Contact: Vijay Zala       v.zala@imperial.ac.uk   
Germany
Justus-Liebig University Active, not recruiting
Giessen, Germany, 35392
United Kingdom
Papworth Hospital NHS Foundation Trust Active, not recruiting
Cambridge, United Kingdom
Hammersmith Hospital, Imperial College NHS Trust Active, not recruiting
London, United Kingdom
Royal Hallamshire Hospital Active, not recruiting
Sheffield, United Kingdom
Sponsors and Collaborators
Imperial College London
Fu Wai Hospital, Beijing, China
Investigators
Principal Investigator: Luke Howard, DPhil, FRCP Imperial College London
  Study Documents (Full-Text)

Documents provided by Imperial College London:
Study Protocol  [PDF] October 24, 2016
Statistical Analysis Plan  [PDF] November 13, 2017


Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01447628     History of Changes
Other Study ID Numbers: CRO1811
First Posted: October 6, 2011    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Imperial College London:
Idiopathic pulmonary arterial hypertension (IPAH)
Iron deficiency

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Anemia, Iron-Deficiency
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Anemia, Hypochromic
Anemia
Hematologic Diseases
Iron Metabolism Disorders
Metabolic Diseases
Iron
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs