Iron Deficiency In Pulmonary Hypertension

Intravenous Iron Treatment In Iron Deficient Patients With Idiopathic Pulmonary Arterial Hypertension

Patients with idiopathic pulmonary arterial hypertension (IPAH) and iron deficiency were previously shown to have a decreased six-minute walking distance. Therefore the investigators hypothesized that intravenous iron administration would improve exercise capacity in iron deficient IPAH patients.

30 patients will be recruited for iron infusions. At baseline and after 12 weeks (endpoint)exercise test will be performed.

Study Overview

• Status: Unknown
• Conditions: Idiopathic Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Ferricarboxymaltose

Detailed Description

Background: Patients with pulmonary arterial hypertension (PAH) develop progressive right heart failure which eventually will lead to death. During progression of the disease the physical performance of the patients deteriorates. Maintaining their exercise capacity is a major goal in PAH treatment. Iron treatment is known to have a positive effect on physical performance in patients with left heart failure and iron deficiency. Whether this is also effective in patients with right heart failure (PAH) and iron deficiency is until now unknown.

Objective: To evaluate the effects of intravenous iron supplementation on exercise capacity in iron deficient IPAH patients.

Study design: Intervention study

Study population: Patients with idiopathic pulmonary arterial hypertension (IPAH) and iron deficiency

Patients receive an iron bolus infusion of 1000 mg iron after baseline measurements.

Main study parameters/endpoints:

Primary endpoint: six minute walking distance (6WMD) Secondary endpoints: cardiopulmonary exercise test, myoglobin concentration in quadriceps muscle, quadriceps muscle fiber strength, serum iron parameters, serum inflammatory parameters, quality of life (QOL), and NYHA functional class.

The patients will be hospitalised two days at the beginning and two days at the end of the study to perform the exercise and strength tests, six minute walking distance and for biopsy of the quadriceps muscle. Also NYHA functional class will be determined and a QOL questionnaire has to be filled in. After the baseline measurements an iron infusion will be given (Ferinject 1000mg).

The investigators hypothesize that iron deficient IPAH patients will benefit from iron treatment with improved exercise capacity reflected in an increased 6MWD.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gerrina Ruiter, MD; Phone Number: +31 20 444 4915; Email: G.Ruiter@vumc.nl
• Study Contact Backup: Name: Anton Vonk-Noordegraaf, Prof MD PhD; Phone Number: +31 20 444 4710; Email: A.Vonk@vumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • VUMC
    • Contact: Gerrina Ruiter, MD; Phone Number: +31 20 444 4915; Email: G.Ruiter@vumc.nl
    • Principal Investigator: Anton Vonk Noordegraaf, Prof MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stable idiopathic pulmonary arterial hypertension (stable disease for at least 3 months)
• iron deficiency (serum iron below 10 μmol/l, decreased transferrin saturation (< 15% in females and < 20% in males) and serum ferritin < 100 μg/l) irrespective of the coexistence of anaemia

Exclusion Criteria:

• Current iron therapy (oral or iv)
• Current other study medication for PAH
• History of anaemia or current treatment for anaemia
• Liver function impairment
• Chronic disease other than PAH (rheumatism, asthma, chronic infection)
• Acute infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
six-minute walking distance	The primary endpoint is improvement in six-minute walking distance	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum iron parameters	Serum iron parameters and inflammatory parameters are measured	0 and 12 weeks
Exercise capacity	Cardiopulmonary exercise testing is performed to measure maximal exercise capacity and exercise endurance time.	0 and 12 weeks
Quadriceps muscle function	A biopsy from the quadriceps muscle is taken for histochemical analysis, myoglobin measurements and muscle fiber strength characteristics	0 and 12 weeks
Cardiac Function	A cardiac MRI is performed to measure cardiac function	0 and 12 weeks
Quality of life	Quality of life and NYHA functional class is established.	0 and 12 weeks

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Vifor Pharma
• Investigators: Principal Investigator: Anton Vonk-Noordegraaf, Prof MD PhD, VU University Medical Center, Deparment of Pulmonology

Publications and helpful links

General Publications

• Ruiter G, Manders E, Happe CM, Schalij I, Groepenhoff H, Howard LS, Wilkins MR, Bogaard HJ, Westerhof N, van der Laarse WJ, de Man FS, Vonk-Noordegraaf A. Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency. Pulm Circ. 2015 Sep;5(3):466-72. doi: 10.1086/682217.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ANTICIPATED): December 1, 2012
• Study Completion (ANTICIPATED): January 1, 2013

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 1, 2011
• First Posted (ESTIMATE): February 2, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 2, 2011
• Last Update Submitted That Met QC Criteria: February 1, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Exercise; Pulmonary arterial hypertension; Iron deficiency
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: 2010-247