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Phase 2 N=56 Randomized Quadruple-blind Treatment

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

Pulmonary Arterial Hypertension · Iron Deficiency

Enrolled (actual)
56
Serious AEs
5.4%
Results posted
Mar 2022
Primary outcome: Primary: Change in Exercise Capacity - Endurance — 315.44; 302.89 Seconds — p=0.6039

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Saline (Drug); Ferinject or CosmoFer (Drug)
Age
Pediatric, Adult, Older Adult · 16+ yrs
Sex
All
Sponsor
Imperial College London
Primary completion
Dec 2017

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Exercise Capacity - Endurance
315.44; 302.89 0.6039
PRIMARY
Change in Resting Pulmonary Vascular Resistance (PVR)
7.69; 5.15; 11.70; 9.5 0.0747
SECONDARY
Oxygen Consumption (VO2) Level at Peak 12 Weeks After Study Treatment
1.17; 1.13; 0.93; 0.94 0.6583
SECONDARY
Oxygen Consumption (VO2) at Metabolic Threshold
10.01; 9.99; 10.91; 11.2 0.7711
SECONDARY
Ventilation / Volume of Exhaled Carbon Dioxide (VE/VCO2 Slope)
41.15; 42.35; 35.06; 36.27 0.1788
SECONDARY
Oxygen Consumption (VO2) / Work Rate (WR) Slope
8.12; 8.04; 5.97; 6.04 0.8688
SECONDARY
Peak Oxygen (O2) Pulse Rate
13.30; 11.92; 6.55; 6.36 0.5465
SECONDARY
Oxygen Consumption (VO2) at the End of Endurance Cardio-pulmonary Exercise Test (CPET)
4.25; 4.49 0.6241
SECONDARY
Oxygen Consumption (VO2) at 3 Minutes
1.29; 1.14 0.4758
SECONDARY
Iron Indices: Serum Iron
17.15; 15.48; 15.81; 14.31 0.2050
SECONDARY
Iron Indices: Transferrin Saturations
26.2; 22; 26.81; 22.88 0.0610
SECONDARY
Iron Indices: Ferritin
150.32; 92.74; 135.06; 65.5 0.0003 sig
SECONDARY
Iron Indices: Soluble Transferrin Receptors (sTfR)
28.37; 37.25 <0.0001 sig
SECONDARY
6 Minute Walk Test: Distance Walked
426.03; 424.3; 478; 474.19 0.8093
SECONDARY
6 Minute Walk Test: Borg Dyspnoea Score After Test
3.24; 3.68; 1.38; 1.28 0.0725
SECONDARY
Iron Indices: N-terminal Pro B-type Natriuretic Peptide (NT-pro-BNP)
307.64; 394.94 0.1115
SECONDARY
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): Symptom Score
7.94; 7.94 0.9790
SECONDARY
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): Activity Score
9.12; 9.18 0.7702
SECONDARY
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR Questionnaire): QoL Score
7.58; 7 0.2219
SECONDARY
Mean Right Atrial Pressure (Cardiac Catheter)
6.56; 10.12; 6.67; 4.5 0.1777
SECONDARY
Oxygen Consumption (VO2) Level at Peak
15.10; 14.67; 14.53; 14.36 0.7625
SECONDARY
Oxygen Consumption (VO2) at Metabolic Threshold
10.01; 9.99; 10.91; 11.2 0.7711
SECONDARY
Stroke Volume (Cardiac Catheter)
77.87; 99.71; 55.11; 54.65 0.9504
SECONDARY
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular End-diastolic Volume
201.35; 203.06 0.4478
SECONDARY
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular End Systolic Volume (RVESV)
124.99; 126.31 0.4590
SECONDARY
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular Stroke Volume (RVSV)
76.46; 76.84 0.8086
SECONDARY
Cardiac Magnetic Resonance Imaging (MRI): Right Ventricular Ejection Fraction (RVEF)
39.89; 39.64 0.6944
SECONDARY
Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular End Diastolic Volume (LVEDV)
117.36; 118.33 0.585
SECONDARY
Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular End Systolic Volume (LVESV)
43.90; 44.43 0.4619
SECONDARY
Cardiac Magnetic Resonance Imaging: Left Ventricular Stroke Volume (LVSV)
43.90; 73.96 0.7721
SECONDARY
Cardiac Magnetic Resonance Imaging (MRI): Left Ventricular Ejection Fraction (LVEF)
63.10; 62.94 0.8332
SECONDARY
Cardiac Magnetic Resonance Imaging: Left Ventricular Mass
72.82; 73.53 0.2651

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. IV iron formulation used in Europe - Ferinject IV iron formulation used in China - CosmoFer

Eligibility Criteria

  • Males or females aged between 16-75 years old
  • Pulmonary Arterial Hypertension (PAH) which is idiopathic, heritable or associated with anorexigens.
  • Iron deficiency (TfR levels > 28.1 nmol/l, where sTfR analysis is available, Ferritin 25mmHg, pulmonary capillary wedge pressure =/ 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 Computed Tomography (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 Human Immunodeficiency Virus (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. Gastro-intestinal 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01447628). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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