NCT01447628

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
56

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Mar 2011

Longer than P75 for phase_2

Geographic Reach
3 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 29, 2011

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

October 4, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 6, 2011

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 22, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 22, 2017

Completed
4.2 years until next milestone

Results Posted

Study results publicly available

March 7, 2022

Completed
Last Updated

March 7, 2022

Status Verified

December 1, 2021

Enrollment Period

6.7 years

First QC Date

October 4, 2011

Results QC Date

September 24, 2019

Last Update Submit

December 13, 2021

Conditions

Pulmonary Arterial HypertensionIron Deficiency

Keywords

Idiopathic pulmonary arterial hypertension (IPAH)Iron deficiency

Outcome Measures

Primary Outcomes (2)

  • Change in Exercise Capacity - Endurance

    Time measured in seconds from start to end of the endurance bicycle cardiopulmonary exercise testing at 80% of the peak work rate. Peak work rate is determined by that achieved at the baseline incremental cardiopulmonary exercise test (CPET). Note that this was the primary end-point of the European study. Endurance CPET was not done in China.

    12 Weeks post study treatment

  • Change in Resting Pulmonary Vascular Resistance (PVR)

    To be measured by cardiac catheterisation in wood units.

    12 weeks post study treatment

Secondary Outcomes (30)

  • Oxygen Consumption (VO2) Level at Peak 12 Weeks After Study Treatment

    12 weeks post study treatment

  • Oxygen Consumption (VO2) at Metabolic Threshold

    12 weeks post study treatment

  • Ventilation / Volume of Exhaled Carbon Dioxide (VE/VCO2 Slope)

    12 weeks post study treatment

  • Oxygen Consumption (VO2) / Work Rate (WR) Slope

    12 weeks post study treatment

  • Peak Oxygen (O2) Pulse Rate

    12 weeks post study treatment

  • +25 more secondary outcomes

Study Arms (2)

Ferinject or CosmoFer followed by Placebo

ACTIVE COMPARATOR

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 IV Iron given at Week 0, Placebo (saline) given at Week 12.

Drug: SalineDrug: Ferinject or CosmoFer

Placebo followed by Ferinject or CosmoFer

PLACEBO COMPARATOR

Placebo comparator Placebo (saline) given at Week 0, IV Iron given at Week 12.

Drug: SalineDrug: Ferinject or CosmoFer

Interventions

SalineDRUG

intravenous, no active drug

Also known as: Placebo
Ferinject or CosmoFer followed by PlaceboPlacebo followed by Ferinject or CosmoFer
Ferinject or CosmoFerDRUG

Intravenous, 1000 mg iron

Also known as: Intravenous Iron
Ferinject or CosmoFer followed by PlaceboPlacebo followed by Ferinject or CosmoFer

Eligibility Criteria

Age16 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

  • Unable to provide informed consent.
  • Clinically-significant renal disease (Creatinine clearance \< 30 ml/min per 1.73 m2 calculated from Chronic Kidney Disease-Epidemiology Collaboration (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 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.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Fuwai Hospital

Beijing, China

Location

Justus-Liebig University

Giessen, 35392, Germany

Location

Papworth Hospital NHS Foundation Trust

Cambridge, United Kingdom

Location

Hammersmith Hospital, Imperial College NHS Trust

London, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

Related Publications (1)

  • Howard LSGE, He J, Watson GMJ, Huang L, Wharton J, Luo Q, Kiely DG, Condliffe R, Pepke-Zaba J, Morrell NW, Sheares KK, Ulrich A, Quan R, Zhao Z, Jing X, An C, Liu Z, Xiong C, Robbins PA, Dawes T, de Marvao A, Rhodes CJ, Richter MJ, Gall H, Ghofrani HA, Zhao L, Huson L, Wilkins MR. Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials. Ann Am Thorac Soc. 2021 Jun;18(6):981-988. doi: 10.1513/AnnalsATS.202009-1131OC.

    PMID: 33735594DERIVED

MeSH Terms

Conditions

Pulmonary Arterial HypertensionIron DeficienciesFamilial Primary Pulmonary Hypertension

Interventions

Sodium Chlorideferric carboxymaltose

Condition Hierarchy (Ancestors)

Hypertension, PulmonaryLung DiseasesRespiratory Tract DiseasesIron Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Limitations and Caveats

Refer to the detailed study description in the protocol section.

Results Point of Contact

Title
Professor Martin Wilkins
Organization
Imperial College London
jacob.bonner@nhs.net
0203 313 8078

Study Officials

  • Luke Howard, DPhil, FRCP

    Imperial College London

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 4, 2011

First Posted

October 6, 2011

Study Start

March 29, 2011

Primary Completion

December 22, 2017

Study Completion

December 22, 2017

Last Updated

March 7, 2022

Results First Posted

March 7, 2022

Record last verified: 2021-12

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)GB(3)DE(1)